Mushrooms and Health Report 2012

Mushrooms
and Health
2012
Report prepared by:
Peter Roupas, Christine Margetts, Pennie Taylor, Debra Krause and Manny Noakes
Pre-Clinical and Clinical Health Substantiation
CSIRO Food and Nutritional Sciences, Australia
Report prepared for:

Mushrooms and Health Global Initiative
July 1, 2012
Commercial in Confidence
Enquiries
All enquiries should be addressed to:
Dr Peter Roupas
Pre-Clinical and Clinical Health Substantiaion
CSIRO Food and Nutritional Sciences
Private Bag 16, 671 Sneydes Road
Werribee, Victoria, 3030
Tel: +61 (3) 9731 3283
E-mail: peter.roupas@csiro.au
Copyright and disclaimer
2012 CSIRO To the extent permitted by law, all rights are reserved and no part of this publication
covered by copyright may be reproduced or copied in any form or by any means except with the written
permission of CSIRO.
Important disclaimer
CSIRO advises that the information contained in this publication comprises general statements based on
scientific research. The reader is advised and needs to be aware that such information may be
incomplete or unable to be used in any specific situation. No reliance or actions must therefore be made
on that information without seeking prior expert professional, scientific and technical advice. To the
extent permitted by law, CSIRO (including its employees and consultants) excludes all liability to any
person for any consequences, including but not limited to all losses, damages, costs, expenses and any
other compensation, arising directly or indirectly from using this publication (in part or in whole) and any
information or material contained in it.
Table of Contents
1. EXECUTIVE SUMMARY ..................................................................................................................................... 7
2. INTRODUCTION ................................................................................................................................................. 12
3. METHODOLOGY ................................................................................................................................................ 13
3.1 EVALUATION OF MEDICAL, SCIENTIFIC AND TECHNOLOGICAL INFORMATION ................................................. 13
3.1.1 Clinical Trials Databases ......................................................................................................................... 14
4. NUTRIENT PROFILING OF MUSHROOMS .................................................................................................. 16
4.1 MACRONUTRIENT AND MICRONUTRIENT CONTENT ........................................................................................... 16
4.2 VITAMINS AND MINERALS ................................................................................................................................. 22
4.2.1 Vitamin D .................................................................................................................................................. 22
4.2.2 Minerals .................................................................................................................................................... 25
4.2.2.1 Selenium .............................................................................................................................................................. 27
5. EFFECTS OF MUSHROOMS AND MUSHROOM COMPONENTS ON HEALTH .................................. 28

5.1 STUDIES IN HUMANS ...................................................................................................................................... 28
5.1.1 ANTI-CANCER STUDIES .................................................................................................................................. 39
5.1.1.1 Breast Cancer ........................................................................................................................................ 40
5.1.1.2 Colorectal Cancer .................................................................................................................................. 42
5.1.1.3 Cervical, Ovarian, Endometrial Cancer ................................................................................................ 44
5.1.1.4 Gastric Cancer ....................................................................................................................................... 44
5.1.1.5 Pancreatic Cancer / Solid Malignancies ............................................................................................... 45
5.1.1.6 Prostate Cancer ..................................................................................................................................... 45
5.1.2 ANTI-MICROBIAL PROPERTIES ....................................................................................................................... 47
5.1.3 ANTI-VIRAL PROPERTIES................................................................................................................................ 48
5.1.4 ASTHMA ......................................................................................................................................................... 48
5.1.5 CARDIOVASCULAR HEALTH ........................................................................................................................... 49
5.1.6 COGNITION / BRAIN HEALTH .......................................................................................................................... 50
5.1.7 CONSTIPATION ................................................................................................................................................ 51
5.1.8 DENTAL HEALTH ............................................................................................................................................ 51
5.1.9 DIABETES ....................................................................................................................................................... 52
5.1.10 DNA DAMAGE ............................................................................................................................................. 52
5.1.11 HEPATITIS ..................................................................................................................................................... 53
5.1.12 IMMUNE FUNCTION ...................................................................................................................................... 53
5.1.13 REPRODUCTIVE HEALTH .............................................................................................................................. 57
5.1.14 SUMMARY OF HUMAN STUDIES .................................................................................................................... 58
6. ANTI-DIABETOGENIC PROPERTIES ............................................................................................................ 59
6.1 Animal model (mouse) studies ..................................................................................................................... 59
6.2 Animal model (rat) studies ........................................................................................................................... 61
6.3 In vitro studies.............................................................................................................................................. 65
6.4 Summary of Anti-Diabetogenic Properties .................................................................................................. 66
7. ANTI-MICROBIAL PROPERTIES ................................................................................................................... 66
7.1 Animal model studies ................................................................................................................................... 66
7.2 In vitro studies.............................................................................................................................................. 67
7.3 Summary of Anti-Microbial Properties ....................................................................................................... 71
8. ANTIOXIDANT PROPERTIES .......................................................................................................................... 71
8.1 PHENOLIC CONTENT .......................................................................................................................................... 75
8.2 ERGOTHIONEINE ................................................................................................................................................ 77
8.3 Summary of Anti-Oxidant Properties........................................................................................................... 78
9. ANTI-VIRAL PROPERTIES .............................................................................................................................. 79
9.1 Summary of Anti-Viral Properties ............................................................................................................... 81
10. EFFECTS ON CARCINOGENESIS ................................................................................................................. 82
10.1 BLADDER CANCER........................................................................................................................................... 82

10.1.1 In vitro studies (human cell lines) ........................................................................................................... 82
10.2 BREAST CANCER ............................................................................................................................................. 82
10.2.1 Animal model studies .............................................................................................................................. 82
10.3 CERVICAL, OVARIAN, ENDOMETRIAL CANCER ............................................................................................... 88
10.4 COLON / COLORECTAL CANCER ...................................................................................................................... 90
10.4.1 Animal model (mouse) studies ................................................................................................................ 90
10.4.2 Animal model (rat) studies ...................................................................................................................... 91
10.5 GASTRIC CANCER ............................................................................................................................................ 96
10.6 LEUKEMIA ....................................................................................................................................................... 97
10.7 LIVER CANCER ................................................................................................................................................ 99
10.7.2 In vitro studies (human cell lines) ......................................................................................................... 100
10.8 LUNG CANCER ............................................................................................................................................... 101
10.8.1 Animal model studies ............................................................................................................................ 101
10.9 ORAL CANCER ............................................................................................................................................... 102
10.10 OVARIAN CANCER ....................................................................................................................................... 103
10.10.1 In vitro studies (human cell lines) ....................................................................................................... 103
10.11 PROSTATE CANCER...................................................................................................................................... 103
10.11.1Animal model (mouse) studies ............................................................................................................. 103
10.11.2 Animal model (rat) studies .................................................................................................................. 104
10.11.3 In vitro studies (human cell lines) ....................................................................................................... 104
10.12 SKIN CANCER .............................................................................................................................................. 107
10.12.1 Animal model (mouse) studies ............................................................................................................ 107
10.12.2 In vitro studies (animal cell lines) ...................................................................................................... 107
10.13 DNA DAMAGE ............................................................................................................................................ 108
10.13.1 Animal model (mouse) studies ............................................................................................................ 108
10.13.2 In vitro studies..................................................................................................................................... 109
10.14 SUMMARY OF ANTI-CANCER PROPERTIES ................................................................................................... 111
11. EFFECTS ON CARDIOVASCULAR HEALTH........................................................................................... 112
11.1 Animal model (mouse) studies ................................................................................................................. 112
11.2 Animal model (rat and larger animal) studies ......................................................................................... 113
11.3 In vitro studies.......................................................................................................................................... 117
11.4 Summary of Cardiovascular Health ........................................................................................................ 118
12. EFFECTS ON NEURODEGENERATIVE DISEASES / COGNITION ..................................................... 118
12.1 Animal model studies ............................................................................................................................... 118
12.2 In vitro studies.......................................................................................................................................... 120
12.3 Summary of Neurodegenerative Diseases / Cognition ............................................................................ 120
13. EFFECTS ON DENTAL HEALTH ................................................................................................................ 120
14. EFFECTS OF EYE HEALTH ......................................................................................................................... 121
15. EFFECTS ON IMMUNE FUNCTION ........................................................................................................... 121
15.1 Animal model (mouse) studies ................................................................................................................. 121
15.2 Animal model (rat) studies ....................................................................................................................... 126
15.3 In vitro studies (human cell lines) ............................................................................................................ 126
15.4 Summary of Immune Function ................................................................................................................. 134
16. EFFECTS ON LIVER HEALTH .................................................................................................................... 134
17. EFFECTS ON OSTEOPOROSIS / BONE MINERAL DENSITY .............................................................. 135

17.3 Summary of Osteoporosis/Bone Mineral Density .................................................................................... 136
18. EFFECTS ON RHEUMATOID ARTHRITIS ............................................................................................... 136
19. EFFECTS ON WOUND HEALING ............................................................................................................... 137
20. PROTECTIVE EFFECTS AGAINST UV-LIGHT ....................................................................................... 139
21. HYPERSENSITIVITY TO MUSHROOMS IN HUMANS .......................................................................... 140
21.1 Summary of Hypersensitivity Studies ....................................................................................................... 143
22. FOOD SAFETY STUDIES ............................................................................................................................... 143
22.1 Animal Model Studies .............................................................................................................................. 145
22.2 Agaritine .................................................................................................................................................. 147
23. MUSHROOM BIOACTIVE COMPOUNDS AND PROPOSED MECHANISMS .................................... 148
24. MUSHROOM VARIETIES EFFECTS ON HEALTH .............................................................................. 150
AGARICUS BISPORUS (COMMON WHITE BUTTON, BROWN / CRIMINI, PORTABELLA)............................................... 150
AGARICUS BLAZEI ................................................................................................................................................. 158
AGARICUS BRASILIENSIS ....................................................................................................................................... 170
AGARICUS SYLVATICUS ......................................................................................................................................... 172
AGROCYBE AEGERITE (BLACK POPLAR, PIOPINNO, CHIODINI) ............................................................................. 173
AGROCYBE CHAXINGU .......................................................................................................................................... 174
ANTRODIA CINNAMOMEA ...................................................................................................................................... 174
AURICULARIA AURICULAR (WOOD EAR) .............................................................................................................. 175
AURICULARIA POLYTRICHA (JEW'S EAR) .............................................................................................................. 176
COPRINUS COMATUS.............................................................................................................................................. 177
CORDYCEPS MILITARIS .......................................................................................................................................... 177
CORDYCEPS SINENSIS (CATERPILLAR MUSHROOM) ............................................................................................... 178
FLAMMULINA VELUTIPES (ENOKI) ........................................................................................................................ 180
GANORDERMA LUCIDUM (REISHI, LINGZHI) ......................................................................................................... 184
GRIFOLA FRONDOSA (MAITAKE) .......................................................................................................................... 198
HERICIUM ERINACEUM (POM POM, LIONS MANE) ............................................................................................... 206
HYPSIZIGUS MARMOREUS (BUNA-SHIMEJI)........................................................................................................... 209
INONOTUS OBLIQUUS (CHAGA) ............................................................................................................................. 212
LECCINUM EXTREMIORIENTALE ............................................................................................................................ 212
LENTINULA EDODES (SHIITAKE) ............................................................................................................................ 213
LYOPHYLLUM CONNATUM .................................................................................................................................... 224
PHELLINUS IGNIARIUS ........................................................................................................................................... 224
PHELLINUS LINTEUS .............................................................................................................................................. 225
PHELLINUS RIMOSUS ............................................................................................................................................. 228
PHELLINUS ROBUSTUS ........................................................................................................................................... 229
PHOLIOTA NAMEKO (NAMEKO) ............................................................................................................................. 229
PLEUROTUS CITRINOPILEATUS .............................................................................................................................. 229
PLEUROTUS CORNUCOPIAE .................................................................................................................................... 230
PLEUROTUS ERYNGII ............................................................................................................................................. 230
PLEUROTUS FERULAE ............................................................................................................................................ 233
PLEUROTUS FLORIDA ............................................................................................................................................. 233
PLEUROTUS NEBRODENSIS..................................................................................................................................... 234
PLEUROTUS OSTREATUS (OYSTER MUSHROOMS) ................................................................................................. 234
PLEUROTUS PULMONARIUS ................................................................................................................................... 238
PODAXIS PISTILLARIS ............................................................................................................................................ 239
SCHIZOPHYLLUM COMMUNE (SPLIT GILLS MUSHROOM)...................................................................................... 240
TREMELLA FUCIFORMIS (WHITE WOOD EAR, WHITE JELLY LEAF) ...................................................................... 241
TRAMETES (=CORIOLUS) VERSICOLOR (TURKEY TAIL, YUNZHI) .......................................................................... 241
VOLVARIELLA VOLVACEA (STRAW MUSHROOM) ................................................................................................. 245
WILD EDIBLE FUNGI.............................................................................................................................................. 246
25. CONCLUSIONS ................................................................................................................................................ 247
26. ABOUT THE AUTHORS ................................................................................................................................. 248
27. APPENDIX COMPOSITIONAL TABLES: RAW, COOKED AND DRIED MUSHROOMS ............. 251
28. REFERENCES .................................................................................................................................................. 300
1. Executive Summary
Nutritional Profiling: The current review of nutritional data identified an additional 31

mushroom varieties (since the 2010 report), which are shown in table 1. This report now
provides nutritional profiles for a total of 103 mushroom varieties.
In comparison to common vegetables, the common white button mushroom (Agaricus

bisporus) is a remarkable source of protein, phosphorus, magnesium and vitamin D. A
recent human clinical trial has demonstrated the bioavailability of vitamin D2 from UV-Birradiated button mushrooms in healthy adults deficient in serum 25-hydroxyvitamin D.
Furthermore, the bioavailability of vitamin D2 from vitamin D2-enhanced button mushrooms
via UV-B irradiation was effective in improving vitamin D status and not different to a vitamin
D2 supplement.
Cultivated mushrooms (e.g. Agaricus bisporus/white, Agaricus bisporus/brown, Lentinus

edodes, Pleurotus ostreatus and others) are a valuable source of several micronutrients
and are a low kilojoule, nutrient-dense food. Mushrooms are low in sodium and high in
glutamate which makes them a useful flavour addition to a low-salt diet. As they are low in
kilojoules, they are ideal for incorporation in weight loss programs.
Mushrooms provide 29% of the recommended daily intake (RDI) for vitamin B2 (riboflavin)
and 23% of the RDI for niacin and are one of the very few foods that provide a natural
source of vitamin D. Biosynthesis of vitamin D levels from ergosterols in mushrooms can be
significantly enhanced by exposure to sunlight or ultraviolet light post-harvest (e.g. during
drying).Vitamin D is an important factor for immune function.
Human Studies: The properties and mechanisms of extracts and bioactive compounds
from mushrooms that have been evaluated in a human population or human cell lines are
discussed in this report. The human trials carried out to date have primarily been smaller
observational studies, although larger, double-blind, placebo controlled human studies have
recently been completed and several others are in progress. In general, the growing data
suggest that the mushrooms and mushroom extracts tested in humans are safe and
generally well-tolerated. The most promising data appear to be those indicating an inverse
relationship between mushroom consumption and breast cancer risk. In vitro and animal
trials have reported an inhibition of aromatase activity and subsequent reduction of estrogen
by mushroom extracts. A decrease in aromatase activity has recently been demonstrated in

a human trial following consumption of Agaricus bisporus (Palomares et al., 2011), which
provides a physiologically-relevant mechanism for effects on estrogen receptor positive
tumors.
Anti-Cancer Properties: Anti-tumor effects, primarily in human cell lines, have been
reported for polysaccharides extracted from various mushrooms. The polysaccharides
generally belong to the beta-glucan family of compounds and appear to exert their antitumorigenic effects via enhancement of cellular immunity. Anti-tumor effects of proteoglycan
fractions from a variety of mushrooms, including Agaricus bisporus, involve the elevation of
natural killer (NK) cell numbers and the stimulation of inducible nitric oxide (NO) synthase
gene expression, which is then followed by NO production in macrophages via activation of
the transcription factor, NF-kappaB. Activation of NK cells is likely via interferon-gamma and
interleukin mediated pathways. While studies in human cell lines provide supporting
evidence, well-designed human clinical trials are required before anti-cancer health
outcomes in humans can be validated. In recent years, a number of human trials have been
undertaken and these are outlined in this report.
Anti-Diabetogenic Effects: The consistency between the effects of mushroom extracts in

diabetic animal models and preliminary data from human trials, which mirror decreases in
plasma glucose, blood pressure, cholesterol and triglyceride concentrations, strengthens
the level of evidence for anti-diabetogenic effects of the studied mushrooms and their
extracts.
Anti-Microbial Properties: Initial studies in humans have suggested anti-microbial

properties of extracts from Agaricus blazei Murill and Ganoderma lucidum, although these
studies did not have adequate controls in the experimental design, and therefore such
effects have not yet been scientifically validated in humans. Anti-microbial effects of a large
number of mushroom varieties and mushroom components on both gram-positive and
gram-negative bacteria have been confirmed via in vitro studies. A small number of studies
in animals have been undertaken and suggest that the anti-microbial effects in vivo may be
mediated via the immune system.
Anti-Oxidant Activity: A recent (2012) comparison of the antioxidant properties and

phenolic profile of the most commonly consumed fresh cultivated mushrooms and their
mycelia produced in vitro: Agaricus bisporus (white and brown), Pleurotus ostreatus
(oyster), Pleurotus eryngii (king oyster) and Lentinula edodes (shiitake) have reported that
Agaricus bisporus (brown) had the highest antioxidant potential in vitro, while L. edodes
possessed the highest reducing power. Significant antioxidant activities in vitro have been
reported in several varieties of mushrooms, with one study reporting antioxidant capacity
comparable to vitamin C. The antioxidant activities appear to be related to the polyphenolic
content. L-ergothioneine is a biologically active antioxidant and its production in mushrooms
can be enhanced by addition of histidine to the growth medium/compost. Ergothioneine has
been shown to have anti-oxidative/anti-inflammatory properties in several edible
mushrooms.
Anti-Viral Properties: Two Phase I/II trials in HIV-positive patients have been undertaken
with lentinan, a beta-glucan from Lentinus edodes. Some side effects were observed at the
highest dosages used, which were not present when infusion was undertaken over a
shorter period. Proteins, peptides and polysaccharopeptides from mushrooms have been
reported to be capable of inhibiting human immunodeficiency virus type 1 (HIV-1) reverse
transcriptase and protease, the two enzymes of paramount importance to the life cycle of
the HIV. Inhibitory effects on hepatitis B and herpes simplex virus type I have also been
reported. The anti-viral effects of mushrooms do not seem to be related to viral adsorption
or virucidal effects (i.e. they do not kill the virus), however a number of studies have
reported inhibitory effects at the initial stage of virus replication.
Cardiovascular Health: A reduction in total cholesterol following mushroom consumption

has been reported in a number of human trials, however, effects on low density lipoprotein
and high-density lipoprotein have generally not been observed. Plasma cholesterol in
animal models has been shown to be reduced by mushroom consumption. The
hypocholesterolemic effect in animal trials appears to be due partly to an increased rate of
low density lipoprotein and high-density lipoprotein catabolism. While some studies have
postulated eritadenine or angiotensin I converting enzyme inhibitory peptides as the
hypocholesterolemic agents, similar effects on cholesterol, and other biomarkers of
cardiovascular risk have been demonstrated by consumption of mushroom fibre.
Immune Function: A recent systematic review of immunomodulatory dietary

polysaccharides concluded that glucan extracts from Trametes Versicolor improved survival
and immune function in human randomised controlled trials of cancer patients, providing a
high level of evidence for these effects. Many of the potential therapeutic effects of
mushrooms and mushroom components on a variety of diseases appear to be directly or
indirectly mediated by enhancing natural immunity of the host via effects on natural killer
(NK) cells, macrophages, via balance of T cells and their cytokine production, and via the
activation of Mitogen Activated Protein Kinase (MAPK) pathways.
Cognition / Brain Health: Although preliminary, data showing protective effects of

mushrooms (Hericium erinaceum) on beta-amyloid peptide toxicity in the brain and mild
cognitive impairment (both precursors to dementia) appear promising. Preliminary human
trials with Hericium erinaceum derivatives showed efficacy in patients with dementia in
improving the Functional Independence Measure score or retarding disease progression. A
trial with 50 to 80-year-old Japanese men and women diagnosed with mild cognitive
impairment reported significantly increased cognitive function scores compared to placebo
during intake. The human trials to date have generally had low statistical power, so these
effects remain to be confirmed in larger well-designed human trials.
Osteoporosis / Bone Health: In vitro studies have reported positive effects of mushroom
extracts on mineralisation of osteoblastic cell lines. Animal studies have reported increased
bone density following consumption of mushroom extracts, while mice fed calcium plus
vitamin D2-enhanced (UV irradiated) mushrooms showed improved bone mineralization
through a direct effect on the bone, and by inducing the expression of calcium-absorbing
genes in the duodenum and kidney.
Hypersensitivity to Mushrooms: Spores of mushrooms are airborne components and can

be the cause of hypersensitivity / respiratory allergy. The small number of cases reported,
primarily in Japan, have usually involved workers in the commercial production of
mushrooms, where air-quality may be poor, and hence this condition has been referred to
as mushroom workers disease. The symptoms for this condition usually improve rapidly,
either without medication, when the affected person is removed from the factory
environment, or after corticosteroid administration via a nasal spray.
Bio-accumulation: Mushrooms can bioaccumulate undesirable levels of compounds such

as mercury and cadmium when grown in polluted ecosystems or on agro-industrial waste
and therefore, the growing conditions are important in maintaining a healthy nutritional
profile for mushrooms.
Food Safety Studies / Agaritine: A number of safety assessments on consumption of

mushrooms and mushroom extracts have recently been undertaken by the European Food
Safety Authority (EFSA), as have several human clinical trials. The human trials carried out
to date have suggested that the mushrooms and mushroom extracts tested are safe and
generally well-tolerated. In general, the data have shown no evidence of clinical problems
10
with respect to blood test results, hepatic and renal function, glucose and lipid metabolism,
blood pressure or DNA toxicity. Similarly, analysis of agaritine from hot-water extracts of the
mushroom Hatakeshimeji showed no clinical effects in a human trial suggesting that the
extract of Hatakeshimeji was safe for consumption.
11
2. Introduction
Alongside the mushrooms long history as a food source is an equally long history of beliefs
about their curative abilities in traditional medicine systemsboth the folk medicine of the
western world and traditional medicine of the orient. Although there are still a limited, but
growing, number of direct human intervention trials, there is a very large number of in vitro and
in vivo animal trials describing a range of possible health benefits including immunomodulatory,
anti-tumor, anti-microbial effects and hypocholesterolemic effects.
Some of the more efficacious compounds in mushrooms are 1,6-branched 1,3--glucans which
have been reported to inhibit tumor growth by stimulating the immune system via activation of
macrophages, via balance of T helper cell populations and subsequent effects on natural killer
(NK), cells and also via cytokine production (Hetland et al., 2011). Other work has implicated
polysaccharides with varying sugars such as beta- and alpha-glucans (Borchers et al. 2008).
Such mushroom polysaccharides are beginning to be evaluated as adjuvant cancer therapy
compounds alongside conventional cancer treatments (Standish et al. 2008).
The mechanisms by which these polysaccharides exert their immunomodulatory effects are not
entirely clear, although structurefunction relationships have been described between antitumor activities and structural characteristics of -D-glucans. These mushroom polysaccharides
generally do not exert cytotoxic effects on tumor cells, but have been shown to enhance hostmediated immunomodulatory responses (reviewed by Wong et al. 2011).
A recent systematic review has also provided evidence for immunomodulatory effects
(increased NK cell activity, effects on IgG, IgM, neutrophil and leukocyte counts) in humans
from oral ingestion of dietary polysaccharides (glucans) from some varieties of mushrooms
(Ramberg et al, 2010), while inhibition of aromatase activity by mushroom extracts (Grube et al.,
2001, Chen et al., 2006) and subsequent reduction of estrogen, is a potential adjuvant therapy
for breast cancer patients with estrogen receptor positive tumors. While the effects and
underlying mechanisms of mushroom polysaccharides in health outcomes have been more
extensively evaluated, bioactive proteins from mushrooms (such as lectins, fungal
immunomodulatory proteins (FIP), ribosome inactivating proteins (RIP), ribonucleases and other
proteins have also been reported to possess similar anti-tumor, anti-viral and
immunomodulatory activities (Xu et al., 2011b).
12
This report evaluates published human trials on mushroom consumption and health outcomes
in order to identify the levels of evidence, and to identify areas where future human dietary
intervention trials are warranted to substantiate the potential effects of mushroom consumption
on human health outcomes. While the report focusses on human studies, animal and in vitro
studies that provide lower levels of evidence are also discussed, particularly where they provide
insights into cellular mechanisms. The latter part of this report identifies and describes the
individual key studies undertaken for several culinary and medicinal mushrooms.
3. Methodology
3.1 Evaluation of Medical, Scientific and Technological Information
The information on mushrooms and health was
sourced via detailed and thorough strategic electronic
searches of medical, scientific and technical literature
based on the mushroom varieties and health
conditions identified in the research proposal. The
systematic literature searches were carried out using
the following databases:
PubMed a service of the US National Library of Medicine that includes over 16 million
citations from the MEDLINE database and other life science journals.
SCOPUS - an abstract database covering 25 million abstracts from over 16,000 journals across
4,000 publishers.
Web of Science 10,000 major journals across 164 scientific disciplines.
CSIRO Electronic Journals Collection (4,000 e-journals).
AGRICOLA - includes bibliographic citations for journal articles, monographs, proceedings,
theses, patents, translations, audiovisual materials, computer software, and technical reports
covering all aspects of primary international information sources in agriculture and related
fields. The literature cited is mainly in English, but over one-third of the database comprises
citations in Western European, Slavic, Asian, and African languages.
The captured records were cross-checked across the above databases as well as with records
13
from Food Science and Technology Abstracts (FSTA), Cambridge Scientific Abstracts (CSA)
and ISI Proceedings. Epidemiological and clinical trials were also included in the review and
evaluations. The journals with high impact factors and scientific credibility are indexed in these
databases. The searches were completed in May 2012 and the database contains papers
published up to this time. Searches for clinical trials were updated on June 15, 2012.
3.1.1 Clinical Trials Databases
The search strategy aimed to find published English language studies. A three-step search
strategy wws utilised to complete the report. An initial limited search of MEDLINE
was undertaken followed by analysis of the text words contained in the title and abstract,
and of the index terms used to describe relevant articles. A second search, using identified
keywords, MESH and index terms, was then undertaken across all included databases.
Thirdly, the reference list of identified reports/trials and articles was searched for additional
studies. The listing of the sources and databases used is provided below.
The following databases were searched for systematic reviews and clinical trials:
Medline on Pub Med
Science Citation Index (searched on CSIRO Network)
Cochrane Central (Database of Systematic Reviews and Cochrane Collaboration

Central Register of Controlled Trials.
Centre for Reviews and Dissemination Databases (Database of Reviews of Effects

(DARE). NHS Economic Evaluation Database (NHS EED), Health Technology
Assessment (HTA) Database) CRD Centre for Reviews and Dissemination.
Joanna Briggs Institute (JBI) Library of Systematic Reviews.
Current ongoing trials and as-yet-unpublished trials that might yield data were identified
using the following databases:
Clinical trials.gov
14
ISRCTN International metaRegister of Current Controlled Trials which includes the

following sub-files:
Action Medical Research (UK)
Medical Research Council (UK)
UK Trials (UK)
The Wellcome Trust (UK)
NIHR Health Technology Assessment Program (HTA) (UK)
NIH Clinical Trials.gov Register
Cochrane Collaboration Central Register of Controlled Trials
Australian and New Zealand Clinical Trials Registry (ANZCTR)
World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP)
portal which includes the following sub-files:
Australian New Zealand Clinical Trials Registry
ClinicalTrials.gov
ISRCTN
Chinese Clinical Trial Registry
Clinical Trials Registry - India
German Clinical Trials Register
Iranian Registry of Clinical Trials
Japan Primary Registries Network
Sri Lanka Clinical Trials Register
The Netherlands National Trial Register
The searches did not include unpublished and non peer-reviewed studies.
15
4. Nutrient Profiling of Mushrooms

4.1 Macronutrient and micronutrient content
The current review of nutritional data identified an additional 31 mushrooms varieties (since the
2010 report), shown in table 1. This report now provides nutritional profiles for a total of 103
mushroom varieties.
Table 1: Mushroom varieties added to 2012 Report

RAW MUSHROOMS
COOKED MUSHROOMS
Common Mushroom (Agaricus Bisphorus)
Common Mushroom (Agaricus Bisphorus)
Mushroom Portabella (Portobello), raw (Can)
Mushrooms, white microwaved (Can)
Mushroom Brown Italian (Crimini) raw (Can)
Boletus edible (Fin)
Matsutake, canned in brine solids (Jap)

Mushroom, golden, Asian, canned in brine, drained
(Aust)
Mushroom, straw, Asian, canned in brine, drained (Aust)
Mushroom Boletus, Russula (Fin)
Mushroom fried Agaricus bisporus (Fin)
Chantarelle (Fin)
Boletus edible, boiled (Fin)
False Morel (Fin)
Mushroom, boiled, drained with salt (Can)
Milk-cap Northern (Fin)
Mushroom, straw, canned, drained solids (Can)
Yanagimatsutake, raw (Jap)
Mushroom Portabella (Portabello), grilled (Can)
Shimeji Honshimeji, raw (Jap)
Mushroom, straw, canned, drained solids (USDA)
Culinary Specialty Mushrooms
Numeisugitake, raw (Jap)
Tamogitake, raw (Jap)
Tree ears, Kiurage, boiled (Jap)
Shimeji Hatakeshimeji, raw (Jap)
Tree ears, Shiro-kikurage, boiled (Jap)
Kuroawabitake, raw (Jap)
Tree ears, Arage-kikurage, boiled (Jap)
Matsutake, raw (Jap)
DRIED MUSHROOMS
Chanterelle, raw (USDA)
Morel, raw (USDA)
Shiitake, dried (Log grown)

Mushroom Milk Caps, salted (Fin)
Of particular interest for this report are the nutrients for which the common mushroom varieties
provide >10% recommended dietary intake (RDI) or Adequate Intake (AI) for Adults 19 years
and over by 100g (20g for dried mushroom varieties) with comprehensive compositional tables
for the macronutrient contents, vitamin and mineral contents of raw/fresh, canned, dried and
culinary specialty varieties of the common mushroom varieties found in Appendix 1 of this
report. The compositional data has been tabulated agains RDIs, EAR (Estimated Average
Requirement) and AIs for females and males of different ages for comparison. Summary tables
are also provided.
16
Table 2. Common mushroom (Agaricus bisporus) macronutrient content - fresh weight 100g,
Australian nutrient composition data.
As shown in Tables 2 and 3, the common white button mushroom is low in energy and a
valuable source of fibre and several micronutrients.
Content
Nutrient
3.3
Protein (g)
0.3
Carbohydrate (g)
0.3
Fat (g)
1.5
Fibre (g)
25 / 103
Energy (kcal/kj)
As a food, mushrooms are low in protein providing 2-3g/100g raw weight. Protein quality of
mushrooms has not been extensively investigated. The amino acid profile of common
mushroom protein suggests the Protein Digestibility Corrected Amino Acid Score (PDCAAS) - a
method of evaluating the protein quality based on the amino acid requirements of humans is
approximately 0.66 assuming a digestibility of 70%. The highest score is 1, which applies to
animal protein sources. As such, this suggests a moderate protein quality. Studies of protein
quality in other species suggest a lower score. Although the concentration of protein in
mushrooms is low, the use of mycoprotein has been exploited in the manufacture of meat
replacement products such as Quorn.
Ten popular species of both edible and medicinal Korean mushrooms have been analysed for
their free amino acids and disaccharides. The average total free amino acid concentration was
121 mg/g in edible mushrooms and 61 mg/g in medicinal mushrooms, respectively. The
average total of free amino acids for all mushrooms, edible mushrooms and medicinal
mushrooms was 91.13 mg/g. Agaricus blazei (227.00 mg/g) showed the highest concentration
of total free amino acids; on the other hand, Inonotus obliquus (2.00 mg/g) showed the lowest
concentration among the 10 species of mushrooms. The average total carbohydrate
concentration was 46.67 mg/g in the 10 species of mushrooms, where the edible mushrooms
17
contained 66.68 mg/g and the medicinal mushrooms contained 26.65 mg/g. The carbohydrate
constituents of the 10 mushroom species were mainly mannose (36.23%), glucose (34.70%),
and xylose (16.83%) (Kim et al., 2009b).
The concentration of vitamin B12 in mushrooms has been controversial. Mushrooms cultivated
on manure-enriched compost may contain vitamin B12 and may be responsible for previous
reports of high B12 levels. However, the USDA database suggests that vitamin B12 at 0.04g
per 100g mushrooms is very low compared to the RDI of 2g/day. Mattila and co-workers
(Mattila et al., 2001) reported levels of 0.05-0.07g. Nevertheless, the presence of any vitamin
B12 is intriguing, as conventionally only animal sources are thought to provide vitamin B12. A
recent study of vitamin B 12 concentrations in Agaricus bisporus reported higher concentrations
of vitamin B12 in the outer peel than in the cap, stalk, or flesh, suggesting that the vitamin B12
is probably bacteria-derived (Koyyalamudi et al., 2009a). High concentrations of vitamin B12
were also detected in the flush mushrooms including cups and flats. HPLC and mass
spectrometry showed the vitamin B12 retention time and mass spectra to be identical to those
of the standard vitamin B12 and those of food products including beef, beef liver, salmon, egg,
and milk but not of the pseudovitamin B12, an inactive corrinoid in humans. Further
investigation of this is warranted.
The micronutrient content of the common mushroom (Agaricus bisporus) is shown in Table 3,
which also shows the estimated average requirement (EAR) and recommended daily intake
(RDI) for Australian adults that is provided by a 100g serve of mushrooms. The nutrients for
which mushrooms provide >10% of the recommended daily intake (RDI) for Australian adults
are riboflavin, niacin, vitamin D, phosphorus and selenium. It is of note that mushrooms provide
26% for males and 31% for females of the recommended daily intake (RDI) for Vitamin B2
(riboflavin) and 23-27% of the RDI for niacin per 100g respectively for adults over 19 years.
Mushrooms remain one of the very few foods that provide a natural source of vitamin D. The
vitamin D levels can be significantly enhanced by sunlight or irradiation. Agaricus bisporus
(USDA) is of particular interest in this area showing that 100g of mushroom exposed to UV light
can provide up to 11.2g of Vitamin D, a significant increase in vitamin D when compared to
non-exposed Agaricus bisporus providing 0.2g (USDA).
In addition, mushrooms provide 22-26% of the RDI for selenium and 20-29% of the adequate
intake (AI) for copper for males and female over 19 years respectively. Mushrooms are also low
in sodium and low in kilojoules.
18
Table 3. Micronutrient content: Fresh weight/100g of common mushroom (Agaricus bisporus) Australian
1
2
nutrient composition data (unless otherwise specified) RDI and EAR for Australian adults >19years of
age.
3
Nutrient
Content
% EAR
% RDI
% EAR
% RDI Female
Male
Male
Female
0.025
3
2
3
2
Thiamin (B1) (mg)
0.37
34
29
41
34
3.72
31
23
34
27
18
0.02
1.15
19 AI
29 AI
8.9
30 AI
36 AI
1.0
13 = 2 g RE
<1
<1
<1
<1
0.2
4 AI
4 AI
0.342
20 AI
29 AI
110
19
11
19
11
11
10
12
0.058
1 AI
1.6
Riboflavin (B2) (mg)
Niacin equivalents (B3) (mg)

Folate (mcg, =g)
Vitamin B6 (mg)
Pantothenic acid (mg)

Biotin (g)
Vitamin C (mg)
Beta-carotene equivalent
8
(g)
Vitamin D (g)
Copper (mg)
10
Phosphorus (mg)
Magnesium (mg)
Manganese (mg)
Molybdenum (g)
Sodium (mg)
8.0
13
310
8 AI
15.4
26
22
31
26
15
0.56
16
0.27
<1
<1
<1
<1
Potassium (mg)
Selenium g)
Zinc (mg)
Iron (mg)
1 AI
Calcium (mg)
Iodine (g)
18
17
14
Nil
11 AI
Nil
Nil
Nil
RDI Recommended Daily Intake

EAR Estimated Average Requirement
3
Percentages have been rounded to whole numbers
4
The RDI and EAR for riboflavin for adults >70 years is higher than adults <70 years
5
The RDI and EAR for Vitamin B6 acid rises after 50 years
6
Adequate Intake (AI) used as no RDI or EAR determined
7
AI used as no RDI or EAR determined
8
6 g all-trans -carotene = 1 g Retinol Equivalent
2
Australian Vit D composition data are not available. USDA data was used. Data from Germany & Canada report higher levels
of Vit D of 1.94g & 1.90 g respectively. AI was used as no RDI or EAR determined. AI rises after 50 years.
10

The RDI and EAR is higher for adults>31 years therefore % RDI/EAR reduce accordingly
12
13
It was not thought meaningful to include a % RDI or EAR for sodium
14
15
Australian zinc composition data not available, US data was used
16
Iron requirements for women reduce after the age of 50
17
Calcium requirements increase after the age of 50 in women and 70 in men
18
Iodine g is 0 in the Australian & USDA data, 3g in the UK data, 1 g in the Finnish & Danish data
11
19
Mushrooms contain valuable amounts of the nutrients biotin and pantothenic acid. Biotin is
necessary for a number of enzyme reactions in the body, deficiency is very unusual and has
been seen rarely in people on total intravenous nutrition. Pantothenic acid is involved in fatty
acid metabolism and is necessary for the production of coenzyme A (CoA). CoA plays an
important role in the synthesis of fatty acids, amino acids (the building blocks of protein), some
hormones and neurotransmitters. Like biotin, deficiency of pantothenic acid is very rare.
Mushrooms are also a good source of potassium. Potassium is an important electrolyte in the
body and is the major cation within cells. It lessens the effect of salt on blood pressure.
However, people with kidney disease should be aware that mushrooms are high in potassium,
as they may need to limit their potassium intake.
The compositional tables (Appendix 1) identify the American nutrient composition data for 100g
of raw weight of common white mushroom (Agaricus Bisporus). The nutrients providing > 10%
of the Recommended Dietary Allowance (RDA) and Allowable Intake (AI) for American males
and females respectively over 19 years using USDA Dietary Reference Intakes are:
Riboflavin (B2) provide 28 -35% RDA
Niacin (B3) providing 23 -26% RDA
Pantothenic acid providing 25-37% AI
Phosphorus providing 9%-9% RDA
Copper providing 19-27% RDA
Selenium providing 13-16% RDA
In comparison with Australian grown mushrooms, the composition for riboflavin, niacin and
pantothenic acid are similar. However, as mushrooms obtain a range of essential nutrients from
soil growing medium such as phosphorus, copper and selenium, there are greater variances
within the composition for these nutrients. Table 4 identifies the absolute mineral content for
these minerals for ease of comparison.
20
Table 4: Key mineral content for 100g raw weight of Agaricus bisporus USDA and Australian data.
Agaricus bisporus data source
Australian composition data

23
USDA Composition data
19
Phosphorus
(mg)
110
86
22
Minerals
Copper
(mg)
0.342
0.318
20
21
Selenium
(g)
15.4
9.3
Key Nutrient Comparisons of the common mushroom white (Agaricus bisporus) vs

commonly consumed vegetables (Australian Data)
The 1995 National Nutrition Survey (NNS) identified that potatoes were the main contributor to
the mean intake of vegetable products and dishes. Other notable vegetables in order of those
most commonly consumed were tomatoes and tomatoe products, carrots and root vegetables,
cabbage, cauliflower and brassica vegetables, peas, corn and beans, with leaf and stalk
vegetables consumed less frequently.
The macronutrient of the common mushroom (Agaricus bisporus) compared to the other
commonly consumed Australian vegetables is displayed in Table 5 and Table 6.
In comparison to common vegetables, the common mushroom (Agaricus bisporus) is a
remarkable source of protein, phosphorus, magnesium and vitamin D.
Table 5 Common mushroom (Agaricus Bisporus) vs. other common vegetables - macronutrient content
per 100g
Protein (g)
Carbohydrate
(g)
Common Mushroom (Agaricus

3.3
0.3
Bisporus)
Corn, sweet, yellow, raw
3.3
18.7
Sweet potato, raw, unprepared
1.57
20.12
Pumpkin, raw
1.0
6.5
Carrots, raw
0.93
9.58
Broccoli, raw
2.82
6.64
Beans, snap, green, raw
1.83
6.97
Potatoes, white, flesh and skin, raw
1.68
15.71
USDA National Nutrient Database for Standard Reference, Release 24 (2011)
19
Fat (g)
Fibre (g)
Energy
(Kcal/KJ)
0.3
1.5
25/103
1.35
0.05
0.1
0.24
0.37
0.22
0.1
2
3
0.5
2.8
2.6
2.7
2.4
86/360
86/359
26/109
41/173
34/141
31/131
69/288
Aust RDI Male and female >19years = 1,000mg/d: USDA RDA Male and female >19years = 700mg/d
Aust RDI Male > 19 years = 1.7mg/d; Female > 19 years = 1.2mg/d: USDA AI male and female >19 years = 0.9mg/d
21
Aust RDI Male > 19 years = 70 g/d Female > 19 years =60 g /d: USDA RDA Male and female >19years = 55g/d
22
Obtained Online NUTTAB 2006 Nutrient Database Mushroom, Common, Raw
23
Obtained USDA Nutrient database - Mushroom, White, Raw
20
21
Table 6 Common mushroom (Agaricus bisporus) micronutrient (vitamin) content per 100g
Australian Nutrient Composition Data Vs Commonly consumed vegetable (Aust and USDA).
Common
Mushroom
(Agaricus Bisporus)
Corn, sweet, yellow,
raw
Sweet potato, raw,
unprepared
Pumpkin, raw
Carrots, raw
Broccoli, raw
Beans, snap, green,
raw
Potatoes, white, flesh
and skin, raw
Thiamin
(B1)
(mg)
0.025
Folate
(mcg)
Vitamin
B6 (mg)
Vitamin
C (mg)
Phosphorus
(mg)
Magnesium
(mg)
Iron
(mg)
Vitamin
D (g)
18
0.02
110
10
0.27
0.2
0.155
42
0.093
6.8
89
37
0.52
NA
0.078
11
0.209
2.4
47
25
0.61
0.05
0.066
0.071
16
19
63
0.061
0.138
0.175
9
5.9
89.2
0.082
33
0.141
12.2
44
35
66
38
12
12
21
25
0.8
0.3
.073
1.03
0.0
0.0
0.0
0.0
0.071
18
0.203
19.7
62
21
0.052
0.0
0.0
The nutritional and health benefits of mushrooms have recently been reviewed (Cheung, 2010).
4.2 Vitamins and Minerals

4.2.1 Vitamin D
A single-blinded, randomized, placebo-controlled trial
(registered at http://germanctr.de as DRKS00000195) in
26 young subjects with serum 25-hydroxyvitamin D
(25OHD) < 50 nmol/l undertaken over a 5 week period has
demonstrated the bioavailability of vitamin D2 from UV-Birradiated button mushrooms in healthy adults deficient in
serum 25-hydroxyvitamin D. Furthermore, the bioavailability of vitamin D2 from vitamin D2enhanced button mushrooms via UV-B irradiation was effective in improving vitamin D status
and not different to a vitamin D2 supplement (Urbain et al., 2011).
Agaricus bisporus mushrooms contain an abundance of ergosterol, which on exposure to UV
irradiation is converted to vitamin D2. A high rate of conversion from ergosterol to vitamin D2
has been reported following a short treatment time (Koyyalamudi et al., 2009b). The stability of
vitamin D2 remained unchanged during storage at 4C and at room temperature over 8 days
indicating no degradation of vitamin D2. Vitamin D2 was well absorbed and metabolized as
shown by the serum response of 25-hydroxyvitamin D in rats fed the irradiated mushrooms.
22
These data are in agreement with an earlier report that showed that Vitamin D2 from UVirradiated mushrooms was well absorbed and metabolized in a rat model system and significant
increases in femur bone mineralization was shown in the presence of vitamin D-2 from
irradiated mushrooms compared with the controls (Jasinghe et al., 2005). A recent randomised
controlled trial of 38 adults consuming ergocalciferol from Agaricus bisporus or supplements for
6 weeks has reported that ergocalciferol was absorbed and metabolized to 25hydroxyergocalciferol (25(OH)D2) but did not affect vitamin D status, because 25hydroxycholecalciferol (25(OH)D3) decreased proportionally in serum (Stephensen et al.,
2012).
Exposing white button mushrooms to ultraviolet B (UVB) light markedly increases their vitamin
D2 content. In weanling female rats, diets containing 2.5% and 5.0% light-exposed mushrooms
significantly raised 25-hydroxyvitamin D (25(OH)D) and suppressed parathyroid hormone levels
compared to control-fed rats or rats fed 5.0% mushroom unexposed to light. Vitamin D2 from
UVB-exposed mushrooms was reported to be bioavailable, safe, and functional in supporting
bone growth and mineralization in a growing rat model without evidence of toxicity (Calvo et al.,
2012). Enrichment of vitamin D2 in Agaricus bisporus white button mushroom using continuous
UV light needs a longer exposure time, which can lead to discoloration, however, exposure of
whole or sliced mushrooms to pulsed UV light significantly increased vitamin D2 without any
observed discoloration (Rao Koyyalamudi et al., 2011).
The effects of UVB on Agaricus bisporus are limited to changes in vitamin D and show no
detrimental changes relative to natural sunlight exposure. On a dry weight basis, no significant
changes in vitamin C, folate, vitamins B 6, vitamin B 5, riboflavin, niacin, amino acids, fatty
acids, ergosterol, or agaritine were observed following UVB processing, while exposure to
sunlight resulted in a 26% loss of riboflavin, evidence of folate oxidation, and unexplained
increases in ergosterol (9.5%) (Simon et al., 2011). Vitamin D2 can be increased by UV-B
exposure during the growth phase of Agaricus bisporus. Growth is unaffected by UV-B. Postharvest exposure to supplementary UV-B resulted in a higher vitamin D2 content of 32 g/100 g
compared to 24 g/100 g obtained from exposure to UV-B during the growth phase (Kristensen
et al., 2012).
The effect of sunlight on the production of vitamin D of indoor-grown mushrooms while drying
has been studied using Lentinus eddoes (Berk.) Singer (Shiitake mushroom), Ganoderma
lucidum (W. Curt.:Fr.) Lloyd (reishi), and Grifola frondosa (Dicks.:Fr.) S.F. Gray (Maitake). Six
to eight hours of sunlight exposure stimulated the production of vitamin D from low levels of
134, 66, and 469 IU, respectively, to 46,000, 2,760, and 31,900 IU vitamin D, respectively. The
23
highest level of vitamin D was produced in Lentinus edodes, whose spore-producing lamellae
were exposed to the sun. Dried mushrooms also elicited vitamin D production subsequent to
sunlight exposure. Vitamin D is also an important factor for immune function and has been
identified as a major mitigating factor in many diseases, so the sunlight-activated biosynthesis
of vitamin D from ergosterols within mushrooms has substantial implications for the mushroom
industry in the context of health (Stamets, 2005).
The generation of Vitamin D2 in edible mushrooms has been studied in fresh Shiitake
mushrooms (Lentinula edodes), Oyster mushrooms (Pleurotus ostreatus), Button mushrooms
(Agaricus bisporus), and Abalone mushrooms (Pleurotus cystidus) following irradiation with
Ultraviolet-A (UV-A; wavelength 315-400nm), Ultraviolet-B (UV-B; wavelength 290-315nm), and
Ultraviolet-C (UV-C; wavelength 190-290nm). Irradiation of each side of the mushrooms for 1h
was found to be the optimum period of irradiation in this conversion. The conversions of
ergosterol to vitamin D2 under UV-A, UV-B, and UV-C were shown to be significantly different.
The highest vitamin D2 content was observed in Oyster mushrooms irradiated with UV-B at
35C and ~80% moisture. Under the same conditions of irradiation, the lowest vitamin D2
content was observed in button mushrooms (Jasinghe and Perera, 2006).
Raw and processed mushroom samples including wild grown (chanterelles and king bolete)
and cultivated samples (white and brown button, Portabella, Shiitake, Oyster) have been
analysed for vitamin D2 content. Chanterelles and king bolete were found to be good sources
of vitamin D2 (0.72.2g/g d.m.) compared with cultivated mushrooms that had a low content
(< 0.1 g/g d.m.). Canned samples of Agaricus bisporus/white were slightly lower in vitamin D2
compared to fresh samples. Irradiation with UV light in the A region (366nm) only slightly
affected vitamin D2 content. In contrast, irradiation with UV light conducted in the C region
(254nm, 02 h, 20cm distance) for fresh white button mushrooms and freeze-dried chanterelles
resulted in vitamin D2 increasing by up to 9-fold (Cantharellus tubaeformis) and 14-fold (A.
bisporus/white), respectively (Teichmann et al., 2007).
A study has also shown that irradiating slices of Agaricus bisporus was a more efficient way of
increasing the vitamin D2 content than irradiating the gill or pileus of whole mushrooms, due to
the larger exposure area. As the irradiation doses increased, the vitamin D2 concentration also
increased for both sliced Agaricus bisporus and sliced Shiitake (Lentinus edodes) (Ko et al.,
2008). An intensity of 1.0 mW/cm2 at a dose of 0.5 J/cm2, the concentration of vitamin D2
produced in Agaricus bisporus was 3.83 g/g dry solids of mushrooms in 8 minutes, whereas
using an intensity of 0.5 mW/cm2 at a dose of 0.5 J/cm2, the concentration of vitamin D 2
produced was 3.75g/g dry solids of mushrooms in 18 min. Post-harvest time did not have a
24
significant effect on vitamin D2 formation in mushrooms that were treated 1 and 4 days after
harvest (Roberts et al., 2008).
4.2.2 Minerals
Mushrooms contain a variety of minerals and trace elements such as potassium, and copper
and vitamins such as riboflavin, niacin, and folates. Amino acid analysis has shown that protein
in a variety of mushrooms contains nutritionally useful quantities of essential amino acids, while
tryptophan is a limiting amino acid in some varieties (Cuptapun et al., 2010).
The content of mineral elements (Ca, K, Mg, Na, P, Cu, Fe, Mn, Cd, Pb, and Se), vitamins (B1,
B2, B12, C, D, folates, and niacin), and certain phenolic compounds (flavonoids, lignans, and
phenolic acids) have been determined in a study of the cultivated mushrooms Agaricus
bisporus/white, Agaricus bisporus/brown, Lentinus edodes, and Pleurotus ostreatus. Cultivated
mushrooms were found to be good sources of vitamin B2, niacin, and folates, with contents
varying in the ranges 1.8-5.1, 31-65, and 0.30-0.64mg/100g dry weight (dw), respectively.
Compared with vegetables, mushrooms are a good source of many mineral elements e.g. the
content of K, P, Zn, and Cu varied in the ranges 26.7-47.3 g/kg, 8.7-13.9 g/kg, 47-92mg/kg, and
5.2-35mg/kg dw, respectively. Agaricus bisporus/brown was shown to contain large amounts of
Se (3.2mg/kg dw) and the levels of Cd were quite high in L. edodes (1.2mg/kg dw). No
flavonoids or lignans were found in the mushrooms analysed in this study from Finland (Mattila
et al., 2001).
Analyses of Agaricus bisporus (brown), in three flushes and at two different harvest times
showed the mean Zn, Fe, P, Mg, K, Na, and Ca contents of both harvests were 8.15-7.07,7.407.96, 1180.93-1038.69, 88.05-76.29, 213.29-238.82, 2652.0-2500.89, and 534.2-554.80 mg/kg,
respectively. In terms of vitamin C, folic acid, thiamin, riboflavin, and niacin, the mean contents
were 6.75-3.97, 0.09-0.08, 0.085-0.09, 0.27-0.29, and 3.62-2.94 mg/kg, respectively. The
estimated volatile components comprised 18- or 16-carbon compounds such as octadecanoic
acid, hexadecanoic acid derivatives, and other important volatiles like di-limonene, n-nonane,
benzendicarboxylic acid, and cis-linoleic acid esters (Caglarirmak, 2009).
The concentrations of minerals in Shiitake mushrooms (Lentinus edodes) are in general lower
than those in the cultivated white mushroom (Agaricus bisporus) and in the Oyster mushroom
(Pleurotus ostreatus). The greatest differences have been reported in the concentrations of
potassium, phosphorus, calcium, copper, strontium, manganese and zinc. The concentrations
are higher in caps than in stipes. The total amino acid content is 15% in caps and 11% in stipes
25
(dry matter). The amounts of the amino acids Phe, Gly, His, Arg, Ile and Met are relatively
higher than in Agaricus fruit bodies (Vetter, 1995).
A study on the copper and zinc contents of 28 species of edible mushrooms (from different
sites in NW Spain) has shown that the element concentrations were species-dependent, with
the highest levels corresponding to the following species: Calvatia utriformis (235.5mg Cu/kg),
Macrolepiota procera (217.8mg Cu/kg), Agaricus macrosporus (217.7mg Cu/kg) and Calvatia
utriformis (265.8mg Zn/kg), Lactarius delicious (231.0mg Zn/kg), and Agaricus macrosporus
(221.3mg Zn/kg) for Cu and Zn, respectively. All mushroom species bioaccumulated copper
and zinc, while some individual samples of the species, such as Hydnum repandum,
Cantharellus cibarius, and Coprinus comatus, were bioexclusors. The hymenophore in
mushrooms showed higher mean levels than the rest of the fruit bodies, with statistically
significant differences. In this study, the copper and zinc concentrations were compared to
literature data and levels set by legislation, with the authors concluding that the consumption of
these mushrooms cannot be considered a toxicological risk, and that they provide an important
nutritional requirement to the diet (Alonso et al., 2003).
Mycelia from Grifola frondosa grown in the presence of non-mycotoxic concentrations of 100
and 200 ppm (parts per million) of Cu or 25 and 50 ppm of Zn accumulated 200-322 ppm and
267-510 ppm of Cu or Zn, respectively. When the enriched metal mycelia were subjected to a
simulated gastrointestinal digestion in vitro, the solubility in the digestive fluids was 642-669
ppm and 102-530 ppm, which represent approximately 32-33% and 0.7-3.5% of the
recommended daily intake (RDI) for Cu and Zn, respectively, in 1 g of mycelium, with the
authors discussing potential uses of the mineral-enriched mycelia in capsules (in the case of
Cu-enriched mycelia) and in food preparations (Figlas et al., 2010). Good bioavailablity of both
copper and zinc from mycelium of Agaricus blazei Murrill equating to very good levels of
recommended daily intakes of these minerals from small amounts of (1g) of this mushroom has
also been reported (Rabinovich et al., 2007).
The possibility of utilizing agro-industrial wastes in the production of edible, high-quality
products (e.g., mushrooms) implies the risk of bringing toxic substances, such as heavy metals,
into the human food chain. Some mushrooms can bioaccumulate undesirable levels of
compounds such as mercury (Alonso et al., 2000) and cadmium (Favero et al., 1990) when
grown in polluted ecosystems. In such environments, cultivated species accumulate lower
levels than wild mushroom species, only because the mean life is shorter.
26
4.2.2.1 Selenium
Selenium (Se) levels in humans are very dependent on the Se-content of consumed food. A
higher intake of selenium can decrease the risk of a number of health problems. The selenium
content of different, common varieties of Agaricus bisporus is very high, and the caps of fruit
bodies have a higher Se content than the stipe. The average cap/stipe Se ratio has been
reported to be 1.29, and the changes of Se concentration during cultivation (in cultivation's
flushes) are not significant (Vetter and Lelley, 2004).
Selenium in selenium-enriched Pleurotus ostreatus has been shown to be highly bioavailable in
a study in Wistar rats (da Silva et al., 2010a). Furthermore, it has been proposed that the
immune-regulatory activity and selenium-containing attribute of proteins from Ganoderma
lucidum or selenium-enriched G. lucidum in the form of selenocysteine and selenomethionine,
may contribute to their antitumor activity (Du et al., 2010).
It has been shown that Pleurotus cornucopiae (Paulet) Rolland and Grifola frondosa (Dicks.:Fr.)
S.F. Gray mushrooms are able to be enriched with selenium by addition of sodium selenite to
the growth substrate. Selenium increased in basidiomata of both mushrooms in direct response
to levels added to the substrate, but greater uptake of selenium occurred with P. cornucopiae
compared to G. frondosa. The results indicated that both mushrooms can be predictably
enriched with selenium to become an excellent nutritional source of selenium (Beelman and
Royse, 2006).
The main subsistent forms of selenium in Se-enriched mycelia are selenoproteins and
selenium-polysaccharides and Se enrichment studies in mushrooms have also reported an
elevation of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and a decrease in
malondialdehyde (MDA) (Song et al., 2009). An increasingly growing database on chemical
forms of selenium of mushrooms indicates that the seleno-compounds include selenocysteine,
selenomethionine, Se-methylselenocysteine, selenite, and several unidentified selenocompounds (Falandysz, 2008).
27
5. Effects of mushrooms and mushroom components on

health
5.1 Studies in Humans
The properties and mechanisms of extracts and bioactive
compounds from mushrooms that have been evaluated in a
human population or human cell lines are outlined in Table 7.
The human trials carried out to date have primarily been
smaller observational studies, although larger, double-blind,
placebo controlled human studies have recently been
completed and several others are in progress. In general, the
growing data suggest that the mushrooms and mushroom
extracts tested in humans are safe and generally well-tolerated.
The most promising data appear to be those indicating an inverse relationship between
mushroom consumption and breast cancer risk, although most of the studies to date are based
on food frequency /diet recalls, which can be affected by recall bias, and therefore, the effects
need to be confirmed via intervention trials involving mushroom consumption. However, in vitro
and animal trials have reported an inhibition of aromatase activity and subsequent reduction of
estrogen by mushroom extracts, which provide a physiologically-relevant mechanism for effects
on estrogen receptor positive tumors. A decrease in aromatase activity has also recently been
demonstrated in a human trial following consumption of Agaricus bisporus (Palomares et al.,
2011), although only a conference abstract is currently available. Preliminary new data showing
protective effects of mushrooms on beta-amyloid peptide toxicity in the brain and mild cognitive
impairment (both precursors to dementia) are promising and warrant further research on the
ability of mushroom consumption to delay the onset of cognitive decline / Alzheimers disease. In
addition to the studies in human population groups and human cell lines provided in Table 1, the
properties and mechanisms of bioactive compounds and mushroom extracts evaluated in animal
models or animal cell lines are provided in Table 8.
28
Table 7: Properties and mechanisms of bioactive compounds and mushroom extracts evaluated in a human population or human cell lines
BIOACTIVE or EXTRACT
MUSHROOM VARIETY
MECHANISM
REFERENCE
(in vitro/ in vivo)

Anti-Cancer (Breast) Ergosterol
Unspecified variety
Increase serum 25 (OH) vitamin D2 levels (in vivo-
Furlanetto 2009
humans)
Aqueous extracts
Agaricus bisporus
Suppress aromatase activity and proliferation of
Grube et al 2001
EFFECT/ DISEASE
STATE
Hydroxylated triterpenes Multiple varieties

Polysaccharopeptides
Ganerderma lucidum
Anti-Cancer
(Colorectal)
Trametes versicolor (Tv)

Polysaccharide extract
Coriolus versicolor
YUNZHI-BC
Unspecified extract
Unspecified extract
Polysaccharide K (PSK)(in
adjunct with immuno-
chemotherapy)
Unspecified bioactive/
extract
Lectin
Yunzhi
extract
Ganoderma lucidum
Aqueous extract
Inonotus obliquus
Agaricus bisporus
Coriolus versicolor CM-10
Agaricus sylvaticus
Agaricus bisporus (ABL)
MCF-7aro cells- hence suggesting a reduction in

oestrogen production (breast cancer cell lines)
Downregulation of Akt/NF-kappaB signalling
Apoptosis (human cell lines)
Suppress oxidative stress stimulated
phosphorylation of Erk1/2 resulting in
downregulation of expression of c-fos & inhibition
of transcription factors AP-1 and NF-kappaB
Phase 1 trial studying the side effects, tolerability
and best dose (clinical trial first registered 2008)
Effect of 3.5g/ day of YUNZHI-BC as a dietary

supplement for breast cancer patients
Decrease of aroamatase activity
Stimulate both innate and adaptive immune
pathways in curatively resected colorectal cancer
(in vivo)
Benefits in haematological and immunological
parameters & reduction in glycemic levels (in vivo)
Inhibit the proliferation of HT29 human colonic
cells (in vitro -in human cells)
Apoptosis (induced by increase in caspase-3
activity) & Anti-inflammatory function in HT-29 in
human carcinoma cells (no toxicity in HT-29 cells
in doses <10mg/ml) (in vivo)
Apoptosis and inhibition of the growth of HT-29
Jiang et al 2008
Wan et al 2008
Thyagarajan et al 2006
NCT00680667
Completed*
NCT00647075
Status unknown
Palomares et al 2011
Oba et al 2007; Sakamoto
et al 2006
Fortes et al 2009
Yu et al 1993
Hong et al 2004
Lee et al 2009b
5.1.1 Anti-Cancer Studies

Anti-tumor effects, primarily in human cell lines, have been reported for polysaccharides
extracted from various mushrooms. The polysaccharides generally belong to the beta-glucan
family of compounds and appear to exert their anti-tumorigenic effects via enhancement of
cellular immunity. Anti-tumor effects of proteoglycan fractions from a variety of mushrooms,
including Agaricus bisporus, involve the elevation of natural killer (NK) cell numbers and the
stimulation of inducible nitric oxide (NO) synthase gene expression, which is then followed by
NO production in macrophages via activation of the transcription factor, NF-kappaB. Activation
of NK cells is likely via interferon-gamma and interleukin mediated pathways. While studies in
human cell lines provide supporting evidence, well-designed human clinical trials are required
before anti-cancer health outcomes in humans can be validated. In recent years, a number of
human trials have been undertaken and these are outlined below.
A systematic review and meta-analysis of randomized, placebo-controlled, double-blind trials to
assess the efficacy of Yun Zhi (YZ) for survival in cancer patients has recently been published.
Thirteen clinical trials were evaluated with the data showing that Yun Zhi resulted in a significant
survival advantage compared with standard conventional anti-cancer treatment alone. Patients
randomized to Yun Zhi, had a 9% absolute reduction in 5-year mortality, resulting in one additional
patient alive for every 11 patients treated. In patients with breast cancer, gastric cancer, or
colorectal cancer treated with chemotherapy, the effects of the combination of Yun Zhi preparation
on the overall 5-year survival rate was more evident, but not in esophageal cancer and
nasophayngeal carcinoma. However, subgroup analysis could not conclude which type of anticancer treatment may maximize the benefit from Yun Zhi. The meta-analysis has provided strong
evidence that Yun Zhi would have survival benefit in cancer patients, particularly in patients with
carcinoma of the breast, gastric and colorectal cancer (Eliza et al., 2012).
A small pilot study of 7 patients undergoing post-operative cancer chemotherapy has reported
that the concomitant administration of Lentinula edodes mycelia extract with chemotherapy is
safe and improves the quality of life and immune function of patients, although these potential
effects remain to be confirmed by larger trials (Yamaguchi et al., 2011).
The effects of Active Hexose Correlated Compound (AHCC) from Lentinula edodes (Shah et
al., 2011) and the use of Phellinus linteus as complementary therapies in patients with cancer
have been reviewed (Sliva, 2010), as have the anti-cancer properties of five commonlyconsumed edible mushrooms: button mushrooms (Agaricus bisporus), A. blazei, Oyster
39
27. Appendix Compositional tables: Raw, Cooked and Dried Mushrooms

Mushroom Nutrient Summary - Notes on Nutrient Tables
RDI (Recommended Dietary Intake)
The average daily dietary intake level that is sufficient to meet the nutrient requirements of nearly all (9798 per cent) healthy individuals in a
particular life stage and gender group.
AI (Adequate Intake) -used when an RDI cannot be determined
The average daily nutrient intake level based on observed or experimentally-determined approximations or estimates of nutrient intake by a
group (or groups) of apparently healthy people that are assumed to be adequate.
RDI/ AIs Taken from Nutrient Reference Values for Australia and New Zealand (2006) Available at http://www.nrv.gov.au
% RDI = an average of the international figures on Agaricus bisporus
NA = Not available
Mushroom information (spelling, names and species) has been entered into the tables exactly as they are shown in references sources. No
attempt has been made to standardize them.
28. References
ABDULLA, M. A., FARD, A. A., SABARATNAM, V., WONG, K., KUPPUSAMY, U. R., AB
N. & ISMAIL, S. 2011. Potential activity of aqueous extract of culinary-medicinal
mane mushroom, Hericium erinaceus (Bull.: Fr.) pers. (Aphyllophoromycetideae
accelerating wound healing in rats. International Journal of Medicinal Mushroom
39.
ABDULLAH, N., ISMAIL, S. M., AMINUDIN, N., SHUIB, A. S. & LAU, B. F. 2012. Evalua
selected culinary-medicinal mushrooms for antioxidant and ACE inhibitory activi
Evidence Based Complementary and Alternative Medicine, 2012, 464238.
ABEL, O., SUZUKI, T., OGAWA, A., AKATI, T., MASUDA, K., KOYAMA, T., YAZAWA, K
KAWAGISHI, H. 2007. Osteoclast forming suppressive compounds from the mu
Agrocybe Chaxingu. Yakugaku Zasshi-Journal of the Pharmaceutical Society of
127, 64-66.
ABRAMS, D. I., COUEY, P., SHADE, S. B., KELLY, M. E., KAMANU-ELIAS, N. & STAM
2011. Antihyperlipidemic effects of Pleurotus ostreatus (oyster mushrooms) in H
individuals taking antiretroviral therapy. BMC Complementary and Alternative M
60.
ACHARYA, K., SAMUI, K., RAI, M., DUTTA, B. B. & ACHARYA, R. 2004. Antioxidant an
oxide synthase activation properties of Auricularia auricula. Indian Journal of Ex
Biology, 42, 538-540.
ADAMS, L. S., PHUNG, S., WU, X. W., KI, L. & CHEN, S. A. 2008. White button mushro
(Agaricus Bisporus) exhibits antiproliferative and proapoptotic properties and inh
prostate tumor growth in athymic mice. Nutrition and Cancer, 60, 744-756.
ADITYA, G., BHADORIYA, S. S., PRIYA, P., JAIN, A. P. & GOPAL, R. 2011. In vitro pre
cataract by oyster mushroom Pleurotus florida extract on isolated goat eye lens.
Journal of Pharmacology, 43, 667-670.
AESUN, S., JEONGSEON, K., SUN-YOUNG, L., GAEUL, K., MI-KYUNG, S., EUN-SOO
JUNGSIL, R. 2010. Dietary mushroom intake and the risk of breast cancer base
hormone receptor status. Nutrition and Cancer, 62, 476-483.
AHMADI, K. & RIAZIPOUR, M. 2009. Ganoderma lucidum induces the expression of CD

on peripheral blood monocytes. Iran J Immunol, 6, 87-91.
AHN, W. S., KIM, D. J., CHAE, G. T., LEE, J. M., BAE, S. M., SIN, J. I., KIM, Y. W., NAM
S. E. & LEE, I. P. 2004. Natural killer cell activity and quality of life were improve
consumption of a mushroom extract, Agaricus blazei Murill Kyowa, in gynecolog
patients undergoing chemotherapy. International Journal of Gynecological Canc
589-594.
AJITH, T. A. & JANARDHANAN, K. K. 2007. Indian medicinal mushrooms as a source o

antioxidant and antitumor agents. Journal of Clinical Biochemistry and Nutrition,
162.
AJITH, T. A., SUDHEESH, N. P., ROSHNY, D., ABISHEK, G. & JANARDHANAN, K. K.

Effect of Ganoderma lucidum on the activities of mitochondrial dehydrogenases
complex I and II of electron transport chain in the brain of aged rats. Experiment
Gerontology, 44, 219-223.
300
AKIHISA, T., FRANZBLAU, S. G., TOKUDA, H., TAGATA, M., UKIYA, M., MATSUZAWA, T.,
METORI, K., KIMURA, Y., SUZUKI, T. & YASUKAWA, K. 2005. Antitubercular activity and
inhibitory effect on Epstein-Barr virus activation of sterols and polyisoprenepolyols from an
edible mushroom, Hypsizigus marmoreus. Biological and Pharmceutical Bulletin, 28, 11171119.
AKIYAMA, H., ENDO, M., MATSUI, T., KATSUDA, I., EMI, N., KAWAMOTO, Y., KOIKE, T. &
BEPPU, H. 2011. Agaritine from Agaricus blazei Murrill induces apoptosis in the leukemic
cell line U937. Biochimica Et Biophysica Acta-General Subjects, 1810, 519-525.
AL-FATIMI, M. A. A., JULICH, W.-D., JANSEN, R. & LINDEQUIST, U. 2006. Bioactive components
of the traditionally used mushroom Podaxis pistillaris. Evidence-Based Complementary
and Alternative Medicine, 3, 87-92.
ALAM, N., YOON, K., LEE, K., LEE, J. & LEE, T. 2011a. Phenolic compounds concentration and
appraisal of antioxidant and antityrosinase activities from the fruiting bodies of Pleurotus
eryngii. Advances in Environmental Biology, 5, 1104-1113.
ALAM, N., YOON, K. N., LEE, J. S., LEE, M. W. & LEE, T. S. 2011b. Pleurotus nebrodensis
ameliorates atherogenic lipid and histological function in hypercholesterolemic rats.
International Journal of Pharmacology, 7, 455-462.
ALAM, N., YOON, K. N. & LEE, T. S. 2011c. Antihyperlipidemic activities of Pleurotus ferulae on
biochemical and histological function in hypercholesterolemic rats. J Res Med Sci, 16, 77686.
ALONSO, J., GARCIA, M. A., PEREZ-LOPEZ, M. & MELGAR, M. J. 2003. The concentrations and
bioconcentration factors of copper and zinc in edible mushrooms. Archives of
Environmental Contamination and Toxicology, 44, 180-188.
ALONSO, J., SALGADO, M. J., GARCIA, M. A. & MELGAR, M. J. 2000. Accumulation of mercury
in edible macrofungi: influence of some factors. Archives of Environmental Contamination
and Toxicology, 38, 158-162.
AMITANI, R., NISHIMURA, K., NIIMI, A., KOBAYASHI, H., NAWADA, R., MURAYAMA, T.,
TAGUCHI, H. & KUZE, F. 1996. Bronchial mucoid impaction due to the monokaryotic
mycelium of Schizophyllum commune. Clinical Infectious Diseases, 22, 146-148.
AMPERE, A., DELHAES, L., SOOTS, J., BART, F. & WALLAERT, B. 2012. Hypersensitivity
pneumonitis induced by Shiitake mushroom spores. Med Mycol.
ANGELI, J. P., RIBEIRO, L. R., BELLINI, M. F. & MANTOVANI, M. S. 2009. Beta-glucan extracted
from the medicinal mushroom Agaricus blazei prevents the genotoxic effects of
benzo[a]pyrene in the human hepatoma cell line HepG2. Arch Toxicol, 83, 81-86.
ANGELI, J. P., RIBEIRO, L. R., GONZAGA, M. L., SOARES SDE, A., RICARDO, M. P., TSUBOY,
M. S., STIDL, R., KNASMUELLER, S., LINHARES, R. E. & MANTOVANI, M. S. 2006.
Protective effects of beta-glucan extracted from Agaricus brasiliensis against chemically
induced DNA damage in human lymphocytes. Cell Biology and Toxicology, 22, 285-291.
AROLA, H., KOIVULA, T., KARVONEN, A. L., JOKELA, H., AHOLA, T. & ISOKOSKI, M. 1999.
Low trehalase activity is associated with abdominal symptoms caused by edible
mushrooms. Scandinavian Journal of Gastroenterology, 34, 898-903.
ASATIANI, M., ELISASHVILI, V., WASSER, S. P., REZNICK, A. Z. & NEVO, E. 2007a. Antioxidant
activity of submerged cultured mycelium extracts of higher basidiomycetes mushrooms.
International Journal of Medicinal Mushrooms, 9, 151-158.
301
ASATIANI, M. D., ELISASHVILI, V. I., WASSER, S. P., REZNICK, A. Z. & NEVO, E. 2007b. Freeradical scavenging activity of submerged mycelium extracts from higher basidiomycetes
mushrooms. Bioscience, Biotechnology and Biochemistry, 71, 3090-3092.
ASATIANI, M. D., WASSER, S. P., NEVO, E., RUIMI, N., MAHAJNA, J. & REZNICK, A. Z. 2011.
The Shaggy Inc Cap Medicinal Mushroom, Coprinus comatus (OFMull.: Fr.) Pers.
(Agaricomycetideae) Substances Interfere with H(2)O(2) Induction of the NF-kappa B
Pathway through Inhibition of I kappa B alpha Phosphorylation in MCF7 Breast Cancer
Cells. International Journal of Medicinal Mushrooms, 13, 19-25.
BABITSKAYA, V. G., BISKO, N. A., SHCHERBA, V. V. & MITROPOLSKAYA, N. Y. 2007. Study of
melanin complex from medicinal mushroom Phellinus robustus (P. Karst.) Bourd. et Galz.
(aphyllophoromycetideae). International Journal of Medicinal Mushrooms, 9, 177-184.
BADOLE, S. L. & BODHANKAR, S. L. 2007. Interaction study of aqueous extract of Pleurotus
pulmonarius (Fr.) Quel-champ with acarbose in alloxan induced diabetic mice. Journal of
Applied Biomedicine, 5, 157-166.
BADOLE, S. L., SHAH, S. N., PATEL, N. M., THAKURDESAI, P. A. & BODHANKAR, S. L. 2006.
Hypoglycemic activity of aqueous extract of Pleurotus pulmonarius in alloxan-induced
diabetic mice. Pharmaceutical Biology, 44, 421-425.
BAE, J. S., JANG, K. H. & JIN, H. K. 2006. Effects of natural polysaccharides on the growth and
peritoneal carcinomatosis of human gastric adenocarcinoma in a nude mouse model.
Cancer Letters, 235, 60-68.
BAE, J. S., PARK, J. W., PARK, S. H., PARK, J. B., RHO, Y. H., RYU, Y. B., LEE, K. S., PARK, K.
H. & BAE, Y. S. 2009. Apoptotic cell death of human leukaemia U937 cells by ubiquinone9 purified from Pleurotus eryngii. Natural Product Research, 23, 1112-1119.
BAE, J. T., SIM, G. S., LEE, D. H., LEE, B. C., PYO, H. B., CHOE, T. B. & YUN, J. W. 2005.
Production of exopolysaccharide from mycelial culture of Grifola frondosa and its inhibitory
effect on matrix metalloproteinase-1 expression in UV-irradiated human dermal fibroblasts.
FEMS Microbiology Letters, 251, 347-354.
BALA, N., AITKEN, E. A. B., FECHNER, N., CUSACK, A. & STEADMAN, K. J. 2011. Evaluation of
antibacterial activity of Australian basidiomycetous macrofungi using a high-throughput 96well plate assay. Pharmaceutical Biology, 49, 492-500.
BAO, H. & YOU, S. 2011. Molecular characteristics of water-soluble extracts from Hypsizigus
marmoreus and their in vitro growth inhibition of various cancer cell lines and
immunomodulatory function in Raw 264.7 cells. Bioscience Biotechnology and
Biochemistry, 75, 891-898.
BAO, H. H., TARBASA, M., CHAE, H. M. & YOU, S. G. 2012. Molecular properties of waterunextractable proteoglycans from Hypsizygus marmoreus and their in vitro
immunomodulatory activities. Molecules, 17, 207-226.
BAO, H. N., USHIO, H. & OHSHIMA, T. 2009. Antioxidative activities of mushroom (Flammulina
velutipes) extract added to bigeye tuna meat: dose-dependent efficacy and comparison
with other biological antioxidants. J Food Sci, 74, C162-9.
BAO, H. N. D., OCHIAI, Y. & OHSHIMA, T. 2010. Antioxidative activities of hydrophilic extracts
prepared from the fruiting body and spent culture medium of Flammulina velutipes.
Bioresource Technology, 101, 6248-6255.
BARBISAN, L. F., MIYAMOTO, M., SCOLASTICI, C., SALVADORI, D. M., RIBEIRO, L. R., EIRA,
A. F. & DE CAMARGO, J. L. 2002. Influence of aqueous extract of Agaricus blazei on rat
liver toxicity induced by different doses of diethylnitrosamine. Journal of
Ethnopharmacology, 83, 25-32.
302
BARBISAN, L. F., SCOLASTICI, C., MIYAMOTO, M., SALVADORI, D. M., RIBEIRO, L. R., DA
EIRA, A. F. & DE CAMARGO, J. L. 2003. Effects of crude extracts of Agaricus blazei on
DNA damage and on rat liver carcinogenesis induced by diethylnitrosamine. Genetics and
Molecular Research, 2, 295-308.
BATBAYAR, S., KIM, M. J. & KIM, H. W. 2011. Medicinal mushroom Lingzhi or Reishi, Ganoderma
lucidum (W.Curt.:Fr.) P. Karst., beta-glucan induces Toll-like receptors and fails to induce
inflammatory cytokines in NF-kappa B inhibitor-treated macrophages. International Journal
of Medicinal Mushrooms, 13, 213-225.
BATTERBURY, M., TEBBS, C. A., RHODES, J. M. & GRIERSON, I. 2002. Agaricus bisporus
(edible mushroom lectin) inhibits ocular fibroblast proliferation and collagen lattice
contraction. Experimental Eye Research, 74, 361-370.
BAUEROVA, K., PAULOVICOVA, E., MIHALOVA, D., SVIK, K. & PONIST, S. 2009. Study of new
ways of supplementary and combinatory therapy of rheumatoid arthritis with
immunomodulators. Glucomannan and Imunoglukan in adjuvant arthritis. Toxicological and
Industrial Health, 25, 329-335.
BEATTIE, K. D., ROUF, R., GANDER, L., MAY, T. W., RATKOWSKY, D., DONNER, C. D., GILL,
M., GRICE, I. D. & TIRALONGO, E. 2010. Antibacterial metabolites from Australian
macrofungi from the genus Cortinarius. Phytochemistry, 71, 948-955.
BEELMAN, R. B. & ROYSE, D. J. 2006. Selenium enrichment of Pleurotus cornucopiae (Paulet)
Rolland and Grifola frondosa (Dicks.:Fr.) S.F. Gray mushrooms. International Journal of
Medicinal Mushrooms, 8, 77-84.
BERGENDIOVA, K., TIBENSKA, E. & MAJTAN, J. 2011. Pleuran (beta-glucan from Pleurotus
ostreatus) supplementation, cellular immune response and respiratory tract infections in
athletes. European Journal of Applied Physiology, 111, 2033-2040.
BERGER, A., REIN, D., KRATKY, E., MONNARD, I., HAJJAJ, H., MEIRIM, I., PIGUET-WELSCH,
C., HAUSER, J., MACE, K. & NIEDERBERGER, P. 2004. Cholesterol-lowering properties
of Ganoderma lucidum in vitro, ex vivo, and in hamsters and minipigs. Lipids in Health and
Disease, 3, 2.
BERNARDSHAW, S., HETLAND, G., ELLERTSEN, L. K., TRYGGESTAD, A. M. & JOHNSON, E.
2005a. An extract of the medicinal mushroom Agaricus blazei Murill differentially stimulates
production of pro-inflammatory cytokines in human monocytes and human vein endothelial
cells in vitro. Inflammation, 29, 147-153.
BERNARDSHAW, S., HETLAND, G., GRINDE, B. & JOHNSON, E. 2006. An extract of the
mushroom Agaricus blazei Murill protects against lethal septicemia in a mouse model of
fecal peritonitis. Shock, 25, 420-425.
BERNARDSHAW, S., JOHNSON, E. & HETLAND, G. 2005b. An extract of the mushroom Agaricus
blazei murill administered orally protects against systemic Streptococcus pneumoniae
infection in mice. Scandinavian Journal of Immunology, 62, 393-398.
BEYNEN, A. C., FIELMICH, A. M., LEMMENS, A. G. & TERPSTRA, A. H. M. 1996. Farm-grown
mushrooms (Agaricus Campestris) in the diet of rats do not affect plasma and liver
cholesterol concentrations. Nahrung, 40, 343-345.
BISEN, P. S., BAGHEL, R. K., SANODIYA, B. S., THAKUR, G. S. & PRASAD, G. 2010. Lentinus
edodes: A Macrofungus with Pharmacological Activities. Current Medicinal Chemistry, 17,
2419-2430.
BOBEK, P., CHORVATHOVA, V. & GINTER, E. 1991. Hypocholesterolemic effect of Oyster
mushroom (Pleurotus Ostreatus) in rat with Streptozotocine diabetes. Biologia, 46, 10251030.
303
BOBEK, P. & GALBAVY, S. 1999. Hypocholesterolemic and antiatherogenic effect of oyster

mushroom (Pleurotus ostreatus) in rabbits. Nahrung, 43, 339-342.
BOBEK, P. & GALBAVY, S. 2001. Effect of pleuran (beta-glucan from Pleurotus ostreatus) on the
antioxidant status of the organism and on dimethylhydrazine-induced precancerous lesions
in rat colon. British Journal of Biomedical Science, 58, 164-168.
BOBEK, P., GINTER, E. & OZDIN, L. 1993a. Oyster Mushroom (Pleurotus-Ostreatus) accelerates
the plasma-clearance of low-density and high-density-lipoproteins in rats. Nutrition
Research, 13, 885-890.
BOBEK, P., GINTER, E., OZDIN, L. & CERVEN, J. 1990. Hypocholesterolemic effect of Oyster
mushroom (Pleurotus-Ostreatus) in rat with hereditary increased sensitiveness to diet
cholesterol. Biologia, 45, 961-966.
BOBEK, P., KUNIAK, L. & OZDIN, L. 1993b. Study on the mechanism of hypolipemic effect of
Oyster mushroom (Pleurotus-Ostreatus) extracts in Syrian-hamster. Biologia, 48, 305-308.
BOBEK, P., NOSALOVA, V. & CERNA, S. 2001. Effect of pleuran (beta-glucan from Pleurotus
ostreatus) in diet or drinking fluid on colitis in rats. Nahrung, 45, 360-363.
BOBEK, P., OZDIN, L. & KAJABA, I. 1997. Dose-dependent hypocholesterolaemic effect of oyster
mushroom (Pleurotus ostreatus) in rats. Physiological Research, 46, 327-329.
BOBOVCAK, M., KUNIAKOVA, R., GABRIZ, J. & MAJTAN, J. 2010. Effect of pleuran (beta-glucan
from Pleurotus ostreatus) supplementation on cellular immune response after intensive
exercise in elite athletes. Applied Physiology, Nutrition and Metabolism, 35, 755-762.
BOH, B. & BEROVIC, M. 2007. Grifola Frondosa (Dicks.: Fr.) Sf Gray (Maitake mushroom):
Medicinal properties, active compounds, and biotechnological cultivation. International
Journal of Medicinal Mushrooms, 9, 89-108.
BOH, B., BEROVIC, M., ZHANG, J. & ZHI-BIN, L. 2007. Ganoderma lucidum and its
pharmaceutically active compounds. Biotechnology Annual Review, 13, 265-301.
BORCHERS, A. T., KRISHNAMURTHY, A., KEEN, C. L., MEYERS, F. J. & GERSHWIN, M. E.
2008. The immunobiology of mushrooms. Experimental Biology and Medicine (Maywood),
233, 259-276.
BRAUER, D., KIMMONS, T. & PHILLIPS, M. 2002. Effects of management on the yield and highmolecular-weight polysaccharide content of shiitake (Lentinula edodes) mushrooms.
Journal of Agricultural and Food Chemistry, 50, 5333-5337.
BUZINA, W., BRAUN, H., FREUDENSCHUSS, K., LACKNER, A., SCHIMPL, K. &
STAMMBERGER, H. 2003. The basidiomycete Schizophyllum commune in paranasal
sinuses. Mycoses, 46, 23-27.
CAGLARIRMAK, N. 2009. Determination of nutrients and volatile constituents of Agaricus Bisporus
(Brown) at different stages. Journal of the Science of Food and Agriculture, 89, 634-638.
CAI, X. Z., PI, Y., ZHOU, X., TIAN, L. F., QIAO, S. Y. & LIN, J. A. 2010. Hepatoma cell growth
inhibition by inducing apoptosis with polysaccharide isolated from Turkey Tail medicinal
mushroom, Trametes versicolor (L.: Fr.) Lloyd (Aphyllophoromycetideae). International
CALVINO, E., MANJON, J. L., SANCHO, P., TEJEDOR, M. C., HERRAEZ, A. & DIEZ, J. C. 2010.
Ganoderma lucidum induced apoptosis in NB4 human leukemia cells: involvement of Akt
and Erk. J Ethnopharmacol, 128, 71-78.
304
CALVO, M. S., BABU, U. S., GARTHOFF, L. H., WOODS, T. O., DREHER, M., HILL, G. &
NAGARAJA, S. 2012. Vitamin D(2) from light-exposed edible mushrooms is safe,
bioavailable and effectively supports bone growth in rats. Osteoporos Int.
CANESI, L., BORGHI, C., STAUDER, M., LINGSTROM, P., PAPETTI, A., PRATTEN, J.,
SIGNORETTO, C., SPRATT, D. A., WILSON, M., ZAURA, E. & PRUZZO, C. 2011. Effects
of fruit and vegetable low molecular mass fractions on gene expression in gingival cells
challenged with Prevotella intermedia and Actinomyces naeslundii. Journal of Biomedicine
and Biotechnology, 230630.
CAO, D., ZHANG, G.-L., NI, W., TENG, H.-L. & LIN, Z.-B. 2006. Effect of Grifola frondosa
(Dicks.:Fr.) S.F.Gray (maitake mushroom) aqueous extract on nitric oxide production
induced by BCG and cytokines in rat hepatocytes. International Journal of Medicinal
Mushrooms, 8, 49-55.
CARRIZO, M. E., CAPALDI, S., PERDUCA, M., IRAZOQUI, F. J., NORES, G. A. & MONACO, H.
L. 2005. The antineoplastic lectin of the common edible mushroom (Agaricus Bisporus)
has two binding sites, each specific for a different configuration at a single epimeric
hydroxyl. Journal of Biological Chemistry, 280, 10614-10623.
CARVAJAL, A., KOEHNLEIN, E. A., SOARES, A. A., ELER, G. J., NAKASHIMA, A. T. A.,
BRACHT, A. & PERALTA, R. M. 2012. Bioactives of fruiting bodies and submerged culture
mycelia of Agaricus brasiliensis (A. blazei) and their antioxidant properties. LWT-Food
Science and Technology, 46, 493-499.
CAVALIERI, C., BOLZONI, L. & BANDINI, M. 2010. Nicotine determination in mushrooms by LCMS/MS with preliminary studies on the impact of drying on nicotine formation. Food Addit
Contam Part A Chem Anal Control Expo Risk Assess, 27, 473-7.
CHA, J. Y., JUN, B. S., YOO, K. S., HAHM, J. R. & CHO, Y. S. 2006. Fermented, Chaga
mushroom (Inonotus Obliquus) effects on hypolipidemia and hepatoprotection in Otsuka
Long-Evans Tokushima Fatty (Oletf) Rats. Food Science and Biotechnology, 15, 122-127.
CHAN, W. K., LAM, D. T. W., LAW, H. K. W., WONG, W. T., KOO, M. W. L., LAU, A. S. Y., LAU, Y.
L. & CHAN, G. C. F. 2005. Ganoderma lucidum mycelium and spore extracts as natural
adjuvants for immunotherapy. Journal of Alternative and Complementary Medicine, 11,
1047-1057.
CHAN, Y., CHANG, T., CHAN, C. H., YEH, Y. C., CHEN, C. W., SHIEH, B. & LI, C. 2007.
Immunomodulatory effects of Agaricus blazei Murill in Balb/cByJ mice. Journal of
Microbiology Immunology and Infection, 40, 201-208.
CHANDRA, L., ALEXANDER, H., TRAORE, D., LUCAS, E. A., CLARKE, S. L., SMITH, B. J.,
LIGHTFOOT, S. A. & KUVIBIDILA, S. 2011a. White button and Shiitake mushrooms
reduce the incidence and severity of collagen-induced arthritis in dilute brown non-Agouti
mice. Journal of Nutrition, 141, 131-136.
CHANDRA, L. C., SMITH, B. J., CLARKE, S. L., MARLOW, D., D'OFFAY, J. M. & KUVIBIDILA, S.
R. 2011b. Differential effects of shiitake- and white button mushroom-supplemented diets
on hepatic steatosis in C57BL/6 mice. Food and Chemical Toxicology, 49, 3074-3080.
CHANG, H., HSIEH, K., YEH, C., TU, Y. & SHEU, F. 2010a. Oral administration of an Enoki
mushroom protein FVE activates innate and adaptive immunity and induces anti-tumor
activity against murine hepatocellular carcinoma. International Immunopharmacology, 10,
239-246.
CHANG, H. H., CHIEN, P. J., TONG, M. H. & SHEU, F. 2007. Mushroom immunomodulatory
proteins possess potential thermal/freezing resistance, acid/alkali tolerance and
dehydration stability. Food Chemistry, 105, 597-605.
305
CHANG, H. H., HSIEH, K. Y., YEH, C. H., TU, Y. P. & SHEU, F. 2010b. Oral administration of an
Enoki mushroom protein FVE activates innate and adaptive immunity and induces antitumor activity against murine hepatocellular carcinoma. International
Immunopharmacology, 10, 239-246.
CHANG, H. L., LEI, L. S., YU, C. L., ZHU, Z. G., CHEN, N. N. & WU, S. G. 2009a. Effect of
Flammulina velutipes polysaccharides on production of cytokines by murine immunocytes
and serum levels of cytokines in tumor-bearing mice. Zhong Yao Cai, 32, 561-563.
CHANG, J. S., SON, J. K., LI, G., OH, E. J., KIM, J. Y., PARK, S. H., BAE, J. T., KIM, H. J., LEE, I.
S., KIM, O. M., KOZUKUE, N., HAN, J. S., HIROSE, M. & LEE, K. R. 2004. Inhibition of
cell cycle progression on HepG2 cells by hypsiziprenol A9, isolated from Hypsizigus
marmoreus. Cancer Letters, 212, 7-14.
CHANG, Y. H., YANG, J. S., YANG, J. L., WU, C. L., CHANG, S. J., LU, K. W., LIN, J. J., HSIA, T.
C., LIN, Y. T., HO, C. C., WOOD, W. G. & CHUNG, J. G. 2009b. Ganoderma lucidum
extracts inhibited leukemia WEHI-3 cells in BALB/c mice and promoted an immune
response in vivo. Biosci Biotechnol Biochem, 73, 2589-94.
CHEN, H. L., JU, Y., LI, J. J. & YU, M. 2012a. Antioxidant activities of polysaccharides from
Lentinus edodes and their significance for disease prevention. International Journal of
Biological Macromolecules, 50, 214-218.
CHEN, J., MA, C., TSAI, P., WANG, Y. & WU, S. 2010a. In vitro antitumor and immunomodulatory
effects of the protein PCP-3A from mushroom Pleurotus citrinopileatus. Journal of
Agricultural and Food Chemistry, 58, 12117-12122.
CHEN, J., MEJIA, E. G. D. & WU, S. 2011a. Inhibitory effect of a glycoprotein isolated from golden
oyster mushroom ( Pleurotus citrinopileatus) on the lipopolysaccharide-induced
inflammatory reaction in RAW 264.7 macrophage. Journal of Agricultural and Food
Chemistry, 59, 7092-7097.
CHEN, J., TOMINAGA, K., SATO, Y., ANZAI, H. & MATSUOKA, R. 2010b. Maitake mushroom (
Grifola frondosa) extract induces ovulation in patients with polycystic ovary syndrome: a
possible monotherapy and a combination therapy after failure with first-line clomiphene
citrate. Journal of Alternative and Complementary Medicine, 16, 1295-1299.
CHEN, J. J., MAO, D., YONG, Y. Y., LI, J. L., WEI, H. & LU, L. 2012b. Hepatoprotective and
hypolipidemic effects of water-soluble polysaccharidic extract of Pleurotus eryngii. Food
Chemistry, 130, 687-694.
CHEN, J. L., CHEN, Y. C., YANG, S. H., KO, Y. F. & CHEN, S. Y. 2009. Immunological alterations
in lupus-prone autoimmune (NZB/NZW) F1 mice by mycelia Chinese medicinal fungus
Cordyceps sinensis-induced redistributions of peripheral mononuclear T lymphocytes. Clin
Exp Med, 9, 277-84.
CHEN, L., PAN, J. Z., LI, X., ZHOU, Y., MENG, Q. L. & WANG, Q. 2011b. Endo-polysaccharide of
Phellinus igniarius exhibited anti-tumor effect through enhancement of cell mediated
immunity. International Immunopharmacology, 11, 255-259.
CHEN, N. H., LIU, J. W. & ZHONG, J. J. 2010c. Ganoderic acid T inhibits tumor invasion in vitro
and in vivo through inhibition of MMP expression. Pharmacological Reports, 62, 150-163.
CHEN, S., OH, S. R., PHUNG, S., HUR, G., YE, I. J., KWOK, S. L., SHRODE, G. E., BELURY, M.,
ADAMS, L. S. & WILLIAMS, D. 2006. Anti-aromatase activity of phytochemicals in White
Button Mushrooms (Agaricus Bisporus). Cancer Research, 66, 12026-12034.
CHEN, S. N., NAN, F. H., CHEN, S., WU, J. F., LU, C. L. & SONI, M. G. 2011c. Safety assessment
of mushroom beta-glucan: subchronic toxicity in rodents and mutagenicity studies. Food
and Chemical Toxicology, 49, 2890-2898.
306
CHEN TAI, I., CHEN, C., LIN, T., TSAI, Y. & NAM, M. 2011a. A 90-day subchronic toxicological
assessment of Antrodia cinnamomea in Sprague-Dawley rats. Food and Chemical
Toxicology, 49, 429-433.
CHEN TAI, I., CHEN, C., LIN, T., WANG, D. & CHEN, C. 2011b. Developmental toxicity
assessment of medicinal mushroom Antrodia cinnamomea T.T. Chang et W.N. Chou
(higher Basidiomycetes) submerged culture mycelium in rats. International Journal of
CHEN, W., ZHAO, Z., CHEN, S.-F. & LI, Y.-Q. 2008. Optimization for the production of
exopolysaccharide from Fomes fomentarius in submerged culture and its antitumor effect
in vitro. Bioresource Technology, 99, 3187-3194.
CHEN, X., WANG, W., LI, S., XUE, J., FAN, L., SHENG, Z. & CHEN, Y. 2010d. Optimization of
ultrasound-assisted extraction of Lingzhi polysaccharides using response surface
methodology and its inhibitory effect on cervical cancer cells. Carbohydrate Polymers, 80,
944-948.
CHERIAN, E., SUDHEESH, N. P., JANARDHANAN, K. K. & PATANI, G. 2009. Free-radical
scavenging and mitochondrial antioxidant activities of Reishi-Ganoderma lucidum (Curt: Fr)
P. Karst and Arogyapacha-Trichopus zeylanicus Gaertn extracts. J Basic Clin Physiol
Pharmacol, 20, 289-307.
CHEUNG, J. K., LI, J., CHEUNG, A. W., ZHU, Y., ZHENG, K. Y., BI, C. W., DUAN, R., CHOI, R.
C., LAU, D. T., DONG, T. T., LAU, B. W. & TSIM, K. W. 2009. Cordysinocan, a
polysaccharide isolated from cultured Cordyceps, activates immune responses in cultured
T-lymphocytes and macrophages: signaling cascade and induction of cytokines. J
Ethnopharmacol, 124, 61-8.
CHEUNG, L. M. & CHEUNG, P. C. K. 2005. Mushroom extracts with antioxidant activity against
lipid peroxidation. Food Chemistry, 89, 403-409.
CHEUNG, P. C. K. 1996a. The hypocholesterolemic effect of extracellular polysaccharide from the
submerged fermentation of mushroom. Nutrition Research, 16, 1953-1957.
CHEUNG, P. C. K. 1996b. The hypocholesterolemic fffect of two edible mushrooms: Auricularia
Auricula (Tree-Ear) and Tremella Fuciformis (White Jelly-Leaf) in hypercholesterolemic
rats. Nutrition Research, 16, 1721-1725.
CHEUNG, P. C. K. 1998. Plasma and hepatic cholesterol levels and fecal neutral sterol excretion
are altered in hamsters fed straw mushroom diets. Journal of Nutrition, 128, 1512-1516.
CHEUNG, P. C. K. 2010. The nutritional and health benefits of mushrooms. Nutrition Bulletin, 35,
292-299.
CHEUNG, P. C. K., WONG, K. H. & LAI, C. K. M. 2011. Immunomodulatory activities of mushroom
sclerotial polysaccharides. Food Hydrocolloids, 25, 150-158.
CHIU, K. W., LAM, A. H. W. & PANG, P. K. T. 1995. Cardiovascular active substances from the
Straw Mushroom, Volvariella Volvacea. Phytotherapy Research, 9, 93-99.
CHO, E. J., HWANG, H. J., KIM, S. W., OH, J. Y., BAEK, Y. M., CHOI, J. W., BAE, S. H. & YUN, J.
W. 2007. Hypoglycemic effects of exopolysaccharides produced by mycelial cultures of two
different mushrooms Tremella fuciformis and Phellinus baumii in ob/ob mice. Applied
Microbiology and Biotechnology, 75, 1257-1265.
CHOI, D. B., CHA, W. S., KANG, S. H. & LEE, B. R. 2004a. Effect of Pleurotus Ferulae extracts on
viability of human lung cancer and cervical cancer cell lines. Biotechnology and Bioprocess
Engineering, 9, 356-361.
307
CHOI, J. H., OZAWA, N., MASUDA, K., KOYAMA, T., YAZAWA, K. & KAWAGISHI, H. 2010.
Suppressing the formation of osteoclasts using bioactive components of the edible
mushroom Leccinum extremiorientale (L. Vass.) Singer (Agaricomycetideae). International
CHOI, S. B., PARK, C. H., CHOI, M. K., JUN, D. W. & PARK, S. 2004b. Improvement of insulin
resistance and insulin secretion by water extracts of Cordyceps militaris, Phellinus linteus,
and Paecilomyces tenuipes in 90% pancreatectomized rats. Bioscience, Biotechnology
and Biochemistry, 68, 2257-2264.
CHOI, Y., LEE, S. M., CHUN, J., LEE, H. B. & LEE, J. 2006a. Influence of heat treatment on the
antioxidant activities and polyphenolic compounds of Shiitake (Lentinus Edodes)
mushroom. Food Chemistry, 99, 381-387.
CHOI, Y. H., YAN, G. H., CHAI, O. H., CHOI, Y. H., ZHANG, X., LIM, J. M., KIM, J. H., LEE, M. S.,
HAN, E. H., KIM, H. T. & SONG, C. H. 2006b. Inhibitory effects of Agaricus blazei on mast
cell-mediated anaphylaxis-like reactions. Biological & Pharmaceutical Bulletin, 29, 13661371.
CHUNG, M. J., CHUNG, C. K., JEONG, Y. & HAM, S. S. 2010. Anticancer activity of subfractions
containing pure compounds of Chaga mushroom (Inonotus obliquus) extract in human
cancer cells and in Balbc/c mice bearing Sarcoma-180 cells. Nutrition Research and
Practice, 4, 177-182.
CIRIC, L., TYMON, A., ZAURA, E., LINGSTROM, P., STAUDER, M., PAPETTI, A., SIGNORETTO,
C., PRATTEN, J., WILSON, M. & SPRATT, D. 2011. In vitro assessment of shiitake
mushroom (Lentinula edodes) extract for its antigingivitis activity. J Biomed Biotechnol,
2011, 507908.
COLLINS, L., ZHU, T., GUO, J., XIAO, Z. J. & CHEN, C.-Y. 2006. Phellinus linteus sensitises
apoptosis induced by doxorubicin in prostate cancer. British Journal of Cancer, 95, 282288.
CUI, B., HAN, L., QU, J. & LV, Y. 2009. Hypoglycemic activity of Grifola frondosa rich in vanadium.
Biological Trace Element Research, 131, 186-191.
CUI, F. J., LI, Y., XU, Y. Y., LIU, Z. Q., HUANG, D. M., ZHANG, Z. C. & TAO, W. Y. 2007.
Induction of apoptosis in SGC-7901 cells by polysaccharide-peptide GFPS1b from the
cultured mycelia of Grifola frondosa GF9801. Toxicology In Vitro, 21, 417-427.
CUPTAPUN, Y., HENGSAWADI, D., MESOMYA, W. & YAIEIAM, S. 2010. Quality and quantity of
protein in certain kinds of edible mushroom in Thailand. Kasetsart Journal, Natural
Sciences, 44, 664-670.
DA SILVA, M. C. S., NAOZUKA, J., OLIVEIRA, P. V., VANETTI, M. C. D., BAZZOLLI, D. M. S.,
COSTA, N. M. B. & KASUYA, M. C. M. 2010a. In vivo bioavailability of selenium in
enriched Pleurotus ostreatus mushrooms. Metallomics, 2, 162-166.
DA SILVA, R. F., BARROS, A. C. D., PLETSCH, M., ARGOLO, A. & DE ARAUJO, B. S. 2010b.
Study on the scavenging and anti-Staphylococcus aureus activities of the extracts,
fractions and subfractions of two Volvariella volvacea strains. World Journal of
Microbiology & Biotechnology, 26, 1761-1767.
DAGLIA, M., PAPETTI, A., MASCHERPA, D., GRISOLI, P., GIUSTO, G., LINGSTROM, P.,
PRATTEN, J., SIGNORETTO, C., SPRATT, D. A., WILSON, M., ZAURA, E. & GAZZANI,
G. 2011. Plant and fungal food components with potential activity on the development of
microbial oral diseases. J Biomed Biotechnol, 2011, 274578.
DE ROMAN, M., BOA, E. & WOODWARD, S. 2006. Wild-gathered fungi for health and rural
livelihoods. Proceedings Of The Nutrition Society, 65, 190-197.
308
DEEPALAKSHMI, K. & MIRUNALINI, S. 2011. Therapeutic properties and current medical usage
of medicinal mushroom: Ganoderma lucidum. International Journal of Pharmaceutical
Sciences and Research, 2, 1922-1929.
DEIANA, M., ROSA, A., CASU, V., PIGA, R., ASSUNTA DESSI, M. & ARUOMA, O. I. 2004. Lergothioneine modulates oxidative damage in the kidney and liver of rats in vivo: studies
upon the profile of polyunsaturated fatty acids. Clinical Nutrition, 23, 183-193.
DELMANTO, R. D., DE LIMA, P. L. A., SUGUI, M. M., DA EIRA, A. F., SALVADORI, D. M. F.,
SPEIT, G. & RIBEIRO, L. R. 2001. Antimutagenic effect of Agaricus Blazei Murrill
mushroom on the genotoxicity induced by cyclophosphamide. Mutation Research-Genetic
Toxicology and Environmental Mutagenesis, 496, 15-21.
DENG, G., LIN, H., SEIDMAN, A., FORNIER, M., D'ANDREA, G., WESA, K., YEUNG, S.,
CUNNINGHAM-RUNDLES, S., VICKERS, A. J. & CASSILETH, B. 2009. A phase I/II trial
of a polysaccharide extract from Grifola frondosa (Maitake mushroom) in breast cancer
patients: immunological effects. Journal of Cancer Research and Clinical Oncology, 135,
1215-1221.
DI NASO, F. C., DE MELLO, R. N., BONA, S., DIAS, A. S., PORAWSKI, M., FERRAZ ADE, B.,
RICHTER, M. F. & MARRONI, N. P. 2010. Effect of Agaricus blazei Murill on the
pulmonary tissue of animals with streptozotocin-induced diabetes. Exp Diabetes Res,
2010, 543926.
DING, C., TIAN, P., JIA, L., LI, Y., DING, X., XIANG, H., XUE, W. & ZHAO, Y. 2009a. The
synergistic effects of C. Sinensis with CsA in preventing allograft rejection. Front Biosci, 14,
3864-71.
DING, C., TIAN, P. & JIN, Z. 2009b. Clinical application and exploration on mechanism of action of
Cordyceps sinesis mycelia preparation for renal transplantation recipients. Chinese Journal
of Integrated Traditional and Western Medicine, 29, 975-978.
DING, Z. Y., LU, Y. J., LU, Z. X., LV, F. X., WANG, Y. H., BIE, X. M., WANG, F. & ZHANG, K. C.
2010. Hypoglycaemic effect of comatin, an antidiabetic substance separated from Coprinus
comatus broth, on alloxan-induced-diabetic rats. Food Chemistry, 121, 39-43.
DIYABALANAGE, T., MULABAGAL, V., MILLS, G., DEWITT, D. L. & NAIR, M. G. 2008. Healthbeneficial qualities of the edible mushroom, Agrocybe Aegerita. Food Chemistry, 108, 97102.
DOSEUNG, L., SEONG-CHEOL, K., DONGHERN, K., JAE HOON, K., SE PILL, P., YOUN-CHUL,
R., MINYOUNG, K., SOMI KIM, C., KEY ZUNG, R. & DONG-SUN, L. 2011. Screening of
Phellinus linteus, a medicinal mushroom, for anti-viral activity. Journal of the Korean
Society for Applied Biological Chemistry, 54, 475-478.
DOTAN, N., RUIMI, N. & MAHAJNA, J. 2010. The pharmaceutical value of the Basidiomycota fungi
Coprinus comatus. Current Trends in Microbiology, 6, 45-53.
DOTAN, N., WASSER, S. P. & MAHAJNA, J. 2011a. The culinary-medicinal mushroom Coprinus
comatus as a natural antiandrogenic modulator. Integrative Cancer Therapies, 10, 148159.
DOTAN, N., WASSER, S. P. & MAHAJNA, J. 2011b. Inhibition of the androgen receptor activity by
Coprinus comatus substances. Nutrition and Cancer, 63, 1316-1327.
DU, M., HU, X. S., ZHAO, G. H. & WANG, C. 2010. Mechanism underlying the antitumor activity of
proteins from the Ling Zhi or Reishi medicinal mushroom, Ganoderma lucidum (W. Curt.:
Fr.) P. Karst. (Aphyllophoromycetideae) in vitro. International Journal of Medicinal
Mushrooms, 12, 133-139.
309
DU, M., WANG, C., HU, X. S. & ZHA, G. H. 2008. Positive effect of selenium on the immune
regulation activity of Ling Zhi or Reishi medicinal mushroom, Ganoderma Lucidum (W.
Curt.: Fr.) P. Karst. (Aphyllophoromycetideae), proteins in vitro. International Journal of
DUBOST, N. J., BEELMAN, R. B., PETERSON, D. & ROYSE, D. J. 2006. Identification and
quantification of ergothioneine in cultivated mushrooms by liquid chromatography-mass
spectroscopy. International Journal of Medicinal Mushrooms, 8, 215-222.
DUBOST, N. J., BEELMAN, R. B. & ROYSE, D. J. 2007. Influence of selected cultural factors and
postharvest storage on ergothioneine content of common button mushroom Agaricus
bisporus (J. Lge) imbach (agaricomycetideae). International Journal of Medicinal
EBINA, T. 2005. Antitumor effects of intratumoral injection of Basidiomycetes preparations. Gan To
Kagaku Ryoho (Cancer and Chemotherapy), 32, 1654-1656.
ECKHARDT, S. G., BAKER, S. D., BRITTEN, C. D., HIDALGO, M., SIU, L., HAMMOND, L. A.,
VILLALONA-CALERO, M. A., FELTON, S., DRENGLER, R., KUHN, J. G., CLARK, G. M.,
SMITH, S. L., MACDONALD, J. R., SMITH, C., MOCZYGEMBA, J., WEITMAN, S., VON
HOFF, D. D. & ROWINSKY, E. K. 2000. Phase I and pharmacokinetic study of irofulven, a
novel mushroom-derived cytotoxin, administered for five consecutive days every four
weeks in patients with advanced solid malignancies. Journal of Clinical Oncology, 18,
4086-4097.
EFSA PANEL ON DIETETIC PRODUCTS, N. & ALLERGIES 2010. Scientific opinion on the safety
of " Lentinus edodes extract" (Lentinex) as a novel food ingredient. EFSA Journal, 8,
Article 1685.
EGHIANRUWA, Q., ODEKANYIN, O. & KUKU, A. 2011. Physicochemical properties and acute
toxicity studies of a lectin from the saline extract of the fruiting bodies of the shiitake
mushroom, Lentinula edodes (Berk). Int J Biochem Mol Biol, 2, 309-17.
EL-FAKHARANY, E. M., HAROUN, B. M., NG, T. B. & REDWAN, E. R. M. 2010. Oyster mushroom
laccase inhibits hepatitis C virus entry into peripheral blood cells and hepatoma cells.
Protein and Peptide Letters, 17, 1031-1039.
EL DINE, R. S., EL HALAWANY, A. M., MA, C. M. & HATTORI, M. 2008. Anti-HIV-1 protease
activity of lanostane triterpenes from the vietnamese mushroom Ganoderma colossum.
Journal of Natural Products, 71, 1022-1026.
EL DINE, R. S., EL HALAWANY, A. M., MA, C. M. & HATTORI, M. 2009. Inhibition of the
dimerization and active site of HIV-1 protease by secondary metabolites from the
Vietnamese mushroom Ganoderma colossum. Journal of Natural Products, 72, 2019-2023.
ELGORASHI, E. E., MAEKAWA, N. & SATOH, H. 2008. In vitro anti-inflammatory activity of
selected Japanese higher Basidiomycetes mushrooms. International Journal of Medicinal
ELIZA, W. L., FAI, C. K. & CHUNG, L. P. 2012. Efficacy of Yun Zhi (Coriolus versicolor) on survival
in cancer patients: Systematic review and meta-analysis. Recent Pat Inflamm Allergy Drug
Discov, 6, 78-87.
ELLERTSEN, L. K., HETLAND, G., JOHNSON, E. & GRINDE, B. 2006. Effect of a medicinal
extract from Agaricus blazei Murill on gene expression in a human monocyte cell line as
examined by microarrays and immuno assays. International Immunopharmacology, 6, 133143.
ENDO, M., BEPPU, H., AKIYAMA, H., WAKAMATSU, K., ITO, S., KAWAMOTO, Y., SHIMPO, K.,
SUMIYA, T., KOIKE, T. & MATSUI, T. 2010a. Agaritine purified from Agaricus blazei Murrill
310
exerts anti-tumor activity against leukemic cells. Biochimica et Biophysica Acta -- General
Subjects, 1800, 669-673.
ENDO, M., BEPPU, H., AKIYAMA, H., WAKAMATSU, K., ITO, S., KAWAMOTO, Y., SHIMPO, K.,
SUMIYA, T., KOIKE, T. & MATSUI, T. 2010b. Agaritine purified from Agaricus blazei Murrill
exerts anti-tumor activity against leukemic cells. Biochimica et Biophysica Acta, 1800, 669673.
ENMAN, J., ROVA, U. & BERGLUND, K. A. 2007. Quantification of the bioactive compound
eritadenine in selected strains of shiitake mushroom (Lentinus edodes). Journal of
EUN HEE, H., YONG PIL, H., HYUNG GYUN, K., JAE HO, C., JI HYE, I., JI HYE, Y., HYUN-UK,
L., SUNG-SIK, C., YOUNG CHUL, C. & HYE GWANG, J. 2011. Inhibitory effect of
Pleurotus eryngii extracts on the activities of allergic mediators in antigen-stimulated mast
cells. Food and Chemical Toxicology, 49, 1416-1425.
EWART, R. B., KORNFELD, S. & KIPNIS, D. M. 1975. Effect of lectins on hormone release from
isolated rat islets of langerhans. Diabetes, 24, 705-714.
EY, J., SCHOMIG, E. & TAUBERT, D. 2007. Dietary sources and antioxidant effects of
ergothioneine. J Agric Food Chem, 55, 6466-74.
FACCIN, L. C., BENATI, F., RINCAO, V. P., MANTOVANI, M. S., SOARES, S. A., GONZAGA, M.
L., NOZAWA, C. & CARVALHO LINHARES, R. E. 2007. Antiviral activity of aqueous and
ethanol extracts and of an isolated polysaccharide from Agaricus brasiliensis against
poliovirus type 1. Letters in Applied Microbiology, 45, 24-28.
FALANDYSZ, J. 2008. Selenium in edible mushrooms. Journal of Environmental Science and
Health. Part C - Environmental Carcinogenesis & Ecotoxicology Reviews, 26, 256-299.
FAN, L. F., SOCCOL, A. T., PANDEY, A. & SOCCOL, C. R. 2007. Effect of nutritional and
environmental conditions on the production of exo-polysaccharide of Agaricus Brasiliensis
by submerged fermentation and Its antitumor activity. LWT-Food Science and Technology,
40, 30-35.
FAN, M. J., LIN, Y. C., SHIH, H. D., YANG, J. S., LIU, K. C., YANG, S. T., LIN, C. Y., WU, R. S. C.,
YU, C. S., KO, Y. C. & CHUNG, J. G. 2011. Crude Extracts of Agaricus brasiliensis Induce
Apoptosis in Human Oral Cancer CAL 27 Cells through a Mitochondria-dependent
Pathway. In Vivo, 25, 355-366.
FANG, N., LI, Q., YU, S., ZHANG, J., HE, L., RONIS, M. J. J. & BADGER, T. M. 2006. Inhibition of
growth and induction of apoptosis in human cancer cell lines by an ethyl acetate fraction
from shiitake mushrooms. Journal of Alternative and Complementary Medicine, 12, 125132.
FANTUZZI, E., ANASTACIO, L. R., NICOLI, J. R., DE PAULA, S. O., ARANTES, R. M. E. &
VANETTI, M. C. D. 2011. Evaluation of Royal Sun Agaricus, Agaricus brasiliensis S.
Wasser et al., aqueous extract in mice challenged with Salmonella enterica Serovar
Typhimurium. International Journal of Medicinal Mushrooms, 13, 281-288.
FANTUZZI, E., ANASTACIO, L. R., NICOLI, J. R., PAULA, S. O. D., ARANTES, R. M. E., MATTA,
S. L. P. D. & VANETTI, M. C. D. 2010. Aqueous extract of culinary-medicinal royal sun
mushroom, Agaricus brasiliensis S. Wasser et al. (Agaricomycetideae) effects on
immunodepression in mice. International Journal of Medicinal Mushrooms, 12, 227-234.
FAVERO, N., BRESSA, G. & COSTA, P. 1990. Response of Pleurotus ostreatus to cadmium
exposure. Ecotoxicology and Environmental Safety, 20, 1-6.
311
FIGLAS, D., ODDERA, M. & CURVETTO, N. 2010. Bioaccumulation and bioavailability of copper
and zinc on mineral-enriched mycelium of Grifola frondosa. J Med Food, 13, 469-75.
FISCHER, B., YAWALKAR, N., BRANDED, K. A., PICHLER, W. J. & HELBLING, A. 2002.
Triggering of atopic dermatitis by spores of the oyster mushroom Pleurotus pulmonarius.
Allergologie, 25, 209-215.
FORLAND, D. T., JOHNSON, E., SAETRE, L., LYBERG, T., LYGREN, I. & HETLAND, G. 2011.
Effect of an extract based on the medicinal mushroom Agaricus blazei Murill on expression
of cytokines and calprotectin in patients with ulcerative colitis and Crohn's disease. Scand
J Immunol, 73, 66-75.
FORLAND, D. T., JOHNSON, E., TRYGGESTAD, A. M. A., LYBERG, T. & HETLAND, G. 2010. An
extract based on the medicinal mushroom Agaricus blazei Murill stimulates monocytederived dendritic cells to cytokine and chemokine production in vitro. Cytokine, 49, 245250.
FORTES, R. C. & NOVAES, M. 2011. The effects of Agaricus sylvaticus fungi dietary
supplementation on the metabolism and blood pressure of patients with colorectal cancer
during post surgical phase. Nutricion Hospitalaria, 26, 176-186.
FORTES, R. C., NOVAES, M., RECOVA, V. L. & MELO, A. L. 2009. Immunological, hematological,
and glycemia effects of dietary supplementation with Agaricus Sylvaticus on patients'
colorectal cancer. Experimental Biology and Medicine, 234, 53-62.
FORTES, R. C., RECOVA, V. L., MELO, A. L. & NOVAES, M. 2010. Life quality of postsurgical
patients with colorectal cancer after supplemented diet with agaricus sylvaticus fungus.
Nutricion Hospitalaria, 25, 586-596.
FRANK, J. A., RIJIN, X., YU, S., FERGUSON, M., HENNINGS, L. J., SIMPSON, P. M., RONIS, M.
J. J., FANG, N., BADGER, T. M. & SIMMEN, F. A. 2006. Effect of Shiitake Mushroom
Dose on Colon Tumorigenesis in Azoxymethane-Treated Male Sprague-Dawley Rats.
Nutrition Research, 26, 138-145.
FROUFE, H. J., ABREU, R. M. & FERREIRA, I. C. 2011. Using molecular docking to investigate
the anti-breast cancer activity of low molecular weight compounds present on wild
mushrooms. SAR QSAR Environ Res, 22, 315-28.
FROUFE, H. J., ABREU, R. M. & FERREIRA, I. C. 2012. Virtual screening of low molecular weight
mushrooms compounds as potential Mdm2 inhibitors. J Enzyme Inhib Med Chem.
FUI, H. Y., SHIEH, D. E. & HO, C. T. 2002. Antioxidant and free radical scavenging activities of
edible mushrooms. Journal of Food Lipids, 9, 35-46.
FUJII, H., NISHIOKA, N., SIMON, R. R., KAUR, R., LYNCH, B. & ROBERTS, A. 2011.
Genotoxicity and subchronic toxicity evaluation of active hexose correlated compound
(AHCC). Regulatory Toxicology and Pharmacology, 59, 237-250.
FUJII, T., MAEDA, H., SUZUKI, F. & ISHIDA, N. 1978. Isolation and characterization of a new
antitumor polysaccharide, KS-2, extracted from culture mycelia of Lentinus edodes.
Journal of Antibiotics (Tokyo), 31, 1079-1090.
FUJIMIYA, Y., GROVEMAN, D. S., TAKEI, Y., SUZUKI, Y. & NOJI, M. 2006. Effects of
polysaccharides isolated from Agaricus brasiliensis (Agaricomycetideae) on splenic
hematopoiesis in mice. International Journal of Medicinal Mushrooms, 8, 129-133.
FUJIMIYA, Y., SUZUKI, Y., KATAKURA, R. & EBINA, T. 1999. Tumor-specific cytocidal and
immunopotentiating effects of relatively low molecular weight products derived from the
basidiomycete, Agaricus blazei Murill. Anticancer Research, 19, 113-118.
312
FUJITA, R., LIU, J., SHIMIZU, K., KONISHI, F., NODA, K., KUMAMOTO, S., UEDA, C., TAJIRI, H.,
KANEKO, S., SUIMI, Y. & KONDO, R. 2005. Anti-androgenic activities of Ganoderma
lucidum. Journal of Ethnopharmacology, 102, 107-112.
FUKUSHIMA, M., NAKANO, M., MORII, Y., OHASHI, T., FUJIWARA, Y. & SONOYAMA, K. 2000.
Hepatic LDL receptor mRNA in rats is increased by dietary mushroom (Agaricus bisporus)
fiber and sugar beet fiber. Journal of Nutrition, 130, 2151-2156.
FUKUSHIMA, M., OHASHI, T., FUJIWARA, Y., SONOYAMA, K. & NAKANO, M. 2001.
Cholesterol-lowering effects of maitake (Grifola frondosa) fiber, shiitake (Lentinus edodes)
fiber, and enokitake (Flammulina velutipes) fiber in rats. Experimental Biology and
Medicine (Maywood), 226, 758-765.
FULLERTON, S. A., SAMADI, A. A., TORTORELIS, D. G., CHOUDHURY, M. S., MALLOUH, C.,
TAZAKI, H. & KONNO, S. 2000. Induction of apoptosis in human prostatic cancer cells with
beta-glucan (Maitake mushroom polysaccharide). Molecular Urology, 4, 7-13.
FURLANETTO, T. W. 2009. Vitamin D2 could be one of the protective phytochemicals.
International Journal of Cancer, 125, 1994.
FURUKAWA, M., MIURA, N. N., ADACHI, Y., MOTOI, M. & OHNO, N. 2006. Effect of Agaricus
brasiliensis S. Wasser et al. (Agarico-mycetideae) on murine diabetic model C57BL/Ksjdb/db. International Journal of Medicinal Mushrooms, 8, 115-128.
GAO, J.-J., MIN, B.-S., AHN, E.-M., NAKAMURA, N., LEE, H.-K. & HATTORI, M. 2002. New
triterpene aldehydes, lucialdehydes A - C, from Ganoderma lucidum and their cytotoxicity
against murine and human tumor cells. Chemical and Pharmaceutical Bulletin, 50, 837840.
GAO, L., SUN, Y., CHEN, C., XI, Y., WANG, J. & WANG, Z. 2007. Primary mechanism of
apoptosis induction in a leukemia cell line by fraction FA-2-b-? prepared from the
mushroom Agaricus blazei Murill. Brazilian Journal of Medical and Biological Research, 40,
1545-1555.
GAO, Y., TANG, W., DAI, X., GAO, H., CHEN, G., YE, J., CHAN, E., HUANG, M. & ZHOU, S.
2005. Immune responses to water-soluble Ling Zhi mushroom Ganoderma lucidum
(W.Curt.:Fr.) P. Karst. Polysaccharides in patients with advanced colorectal cancer.
GAO, Y., TANG, W., GAO, H., CHAN, E., LAN, J. & ZHOU, S. 2004. Ganoderma lucidum
polysaccharide fractions accelerate healing of acetic acid-induced ulcers in rats. Journal of
Medicinal Food, 7, 417-421.
GAULLIER, J. M., SLEBODA, J., OFJORD, E. S., ULVESTAD, E., NURMINIEMI, M., MOE, C.,
ALBREKTSEN, T. & GUDMUNDSEN, O. 2011. Supplementation with a soluble betaglucan exported from Shiitake medicinal mushroom, Lentinus edodes (Berk.) Singer
Mycelium: A crossover, placebo-controlled study in healthy elderly. International Journal of
GAZZANI, G., DAGLIA, M. & PAPETTI, A. 2011. Food components with anticaries activity. Curr
Opin Biotechnol.
GHALY, I. S., AHMED, E. S., BOOLES, H. F., FARAG, I. M. & NADA, S. A. 2011. Evaluation of
antihyperglycemic action of oyster mushroom (Pleurotus ostreatus) and its effect on DNA
damage, chromosome aberrations and sperm abnormalities in streptozotocin-induced
diabetic rats. Global Veterinaria, 7, 532-544.
GIRIDHARAN, V. V., THANDAVARAYAN, R. A. & KONISHI, T. 2011. Amelioration of scopolamine
induced cognitive dysfunction and oxidative stress by Inonotus obliquus - a medicinal
mushroom. Food and Function, 2, 320-327.
313
GONCALVES, J. L., ROMA, E. H., GOMES-SANTOS, A. C., AGUILAR, E. C., CISALPINO, D.,
FERNANDES, L. R., VIEIRA, A. T., OLIVEIRA, D. R., CARDOSO, V. N., TEIXEIRA, M. M.
& ALVAREZ-LEITE, J. I. 2011. Pro-inflammatory effects of the mushroom Agaricus blazei
and its consequences on atherosclerosis development. European Journal of Nutrition.
GONZAGA, M. L., BEZERRA, D. P., ALVES, A. P., DE ALENCAR, N. M., MESQUITA RDE, O.,
LIMA, M. W., SOARES SDE, A., PESSOA, C., DE MORAES, M. O. & COSTA-LOTUFO, L.
V. 2009. In vivo growth-inhibition of Sarcoma 180 by an alpha-(1-->4)-glucan-beta-(1-->6)glucan-protein complex polysaccharide obtained from Agaricus blazei Murill. Natural
Medicines (Tokyo) - Shoyakugaku Zasshi, 63, 32-40.
GOPAKUMAR, G., MARTIN, F., ANTONY, S. K., PILLAI, T. G. & NAIR, C. K. K. 2010. Preclinical
studies on the use of medicinal mushroom Ganoderma lucidum as an adjuvant in
radiotherapy of cancer. Current Science, 99, 1084-1090.
GORDON, M., BIHARI, B., GOOSBY, E., GORTER, R., GRECO, M., GURALNIK, M., MIMURA, T.,
RUDINICKI, V., WONG, R. & KANEKO, Y. 1998. A placebo-controlled trial of the immune
modulator, lentinan, in HIV-positive patients: a phase I/II trial. Journal of Medicine, 29, 305330.
GRAY, A. M. & FLATT, P. R. 1998. Insulin-releasing and insulin-like activity of Agaricus
Campestris (mushroom). Journal of Endocrinology, 157, 259-266.
GRUBE, B. J., ENG, E. T., KAO, Y. C., KWON, A. & CHEN, S. 2001. White button mushroom
phytochemicals inhibit aromatase activity and breast cancer cell proliferation. Journal of
Nutrition, 131, 3288-3293.
GU, C. Q., LI, J. & CHAO, F. H. 2006. Inhibition of hepatitis B virus by D-fraction from Grifola
frondosa: synergistic effect of combination with interferon-alpha in HepG2 2.2.15. Antiviral
Research, 72, 162-165.
GU, C. Q., LI, J. W., CHAO, F., JIN, M., WANG, X. W. & SHEN, Z. Q. 2007. Isolation, identification
and function of a novel anti-HSV-1 protein from Grifola frondosa. Antiviral Research, 75,
250-257.
GU, Y.-H. & BELURY, M. A. 2005. Selective induction of apoptosis in murine skin carcinoma cells
(CH72) by an ethanol extract of Lentinula edodes. Cancer Letters, 220, 21-28.
GU, Y. H. & LEONARD, J. 2006. In vitro effects on proliferation, apoptosis and colony inhibition in
ER-dependent and ER-independent human breast cancer cells by selected mushroom
species. Oncology Reports, 15, 417-423.
GUAN-JHONG, H., JENG-SHYAN, D., SHYH-SHYUN, H. & MIAO-LIN, H. 2011. Hispolon induces
apoptosis and cell cycle arrest of human hepatocellular carcinoma Hep3B cells by
modulating ERK phosphorylation. Journal of Agricultural and Food Chemistry, 59, 71047113.
GUAN, G. P., WANG, H. X. & NG, T. B. 2007. A novel ribonuclease with antiproliferative activity
from fresh fruiting bodies of the edible mushroom Hypsizigus marmoreus. Biochimica et
Biophysica Acta, 1770, 1593-1597.
GUILLAMON, E., GARCIA-LAFUENTE, A., LOZANO, M., D'ARRIGO, M., ROSTAGNO, M. A.,
VILLARES, A. & MARTINEZ, J. A. 2010. Edible mushrooms: role in the prevention of
cardiovascular diseases. Fitoterapia, 81, 715-723.
GUO, J. J., ZHU, T. B., COLLINS, L., XIAO, Z. X. J., KIM, S. H. & CHEN, C. Y. 2007. Modulation of
lung cancer growth arrest and apoptosis by Phellinus Linteus. Molecular Carcinogenesis,
46, 144-154.
314
GUO, J. Y., HAN, C. C. & LIU, Y. M. 2010. A contemporary treatment approach to both diabetes
and depression by Cordyceps sinensis, rich in vanadium. Evidence-Based Complementary
and Alternative Medicine, 7, 387-389.
GUO, J. Y., LI, C. Y., WANG, J., LIU, Y. M. & ZHANG, J. H. 2011. Vanadium-enriched Cordyceps
sinensis, a contemporary treatment approach to both diabetes and depression in rats.
Evidence-Based Complementary and Alternative Medicine, 1-6.
HA, J. H., BYUN, D. G., KIM, S. M., YOO, C. H. & PARK, C. J. 2003. Shiitake dermatitis in Korea;
clinical and histopathologic study. Korean Journal of Dermatology, 41, 440-444.
HABRANT, D., POIGNY, S., SEGUR-DERAI, M., BRUNEL, Y., HEURTAUX, B., LE GALL, T.,
STREHLE, A., SALADIN, R., MEUNIER, S., MIOSKOWSKI, C. & WAGNER, A. 2009.
Evaluation of antioxidant properties of monoaromatic derivatives of pulvinic acids. J Med
Chem, 52, 2454-64.
HACKMAN, R. M., SHI, X. B., WHITE, R. W. D. & SUN, B. X. 2001. A high genistein, Shiitake
mushroom extract displays anti-tumor effects on prostate and other cancers. FASEB
Journal: Official publication of the Federation of American Societies for Experimental
Biology, 15, A619.
HAN, C. & CUI, B. 2012. Pharmacological and pharmacokinetic studies with Agaricoglycerides,
extracted from Grifola frondosa, in animal models of pain and inflammation. Inflammation.
HAN, C. & LIU, T. 2009. A comparison of hypoglycemic activity of three species of basidiomycetes
rich in vanadium. Biological Trace Element Research, 127, 177-182.
HAN, C., ZHANG, G., WANG, H. & NG, T. 2010. Schizolysin, a hemolysin from the split gill
mushroom Schizophyllum commune. FEMS Microbiology Letters, 309, 115-121.
HAN, C. H., LIU, Q. H., NG, T. B. & WANG, H. X. 2005. A novel homodimeric lactose-binding lectin
from the edible split gill medicinal mushroom Schizophyllum commune. Biochemical and
Biophysical Research Commununications, 336, 252-257.
HAN, E., OH, J. & PARK, H. 2011. Cordyceps militaris extract suppresses dextran sodium sulfateinduced acute colitis in mice and production of inflammatory mediators from macrophages
and mast cells. Journal of Ethnopharmacology, 134, 703-710.
HAN, S.-B., LEE, C. W., KANG, J. S., YOON, Y. D., LEE, K. H., LEE, K., PARK, S.-K. & KIM, H. M.
2006. Acidic polysaccharide from Phellinus linteus inhibits melanoma cell metastasis by
blocking cell adhesion and invasion. International Immunopharmacology, 6, 697-702.
HANADA, K. & HASHIMOTO, I. 1998. Flagellate mushroom (Shiitake) dermatitis and
photosensitivity. Dermatology, 197, 255-257.
HANAOKA, R., UENO, Y., TANAKA, S., NAGAI, K., ONITAKE, T., YOSHIOKA, K. & CHAYAMA,
K. 2011. The water-soluble extract from cultured medium of Ganoderma lucidum (Reishi)
Mycelia (designated as MAK) ameliorates murine colitis induced by trinitrobenzene
sulphonic acid. Scandinavian Journal of Immunology, 74, 454-462.
HANDAYANI, D., CHEN, J., MEYER, B. J. & HUANG, X. F. 2011. Dietary Shiitake mushroom
(Lentinus edodes) prevents fat deposition and lowers triglyceride in rats fed a high-fat diet.
Journal of Obesity, 2011, 258051.
HARADA, A., NAGAI, T. & YAMAMOTO, M. 2011. Production of GABA-enriched powder by a
brown variety of Flammulina velutipes (Enokitake) and its antihypertensive effects in
spontaneously hypertensive rats. Nippon Shokuhin Kagaku Kogaku Kaishi = Journal of the
Japanese Society for Food Science and Technology, 58, 446-450.
315
HARADA, K., ITASHIKI, Y., TAKENAWA, T. & UEYAMA, Y. 2010. Effects of Lentinan alone and in
combination with fluoropyrimidine anticancer agent on growth of human oral squamous cell
carcinoma in vitro and in vivo. International Journal of Oncology, 37, 623-631.
HARHAJI, L., MIJATOVIC, S., MAKSIMOV-IVANIC, D., STOJANOVIC, I., MOMCILOVIC, M.,
MAKSIMOVIC, V., TUFEGDZIC, S., MARJANOVIC, Z., MOSTARICA-STOJKOVIC, M.,
VUCINIC, Z. & STOSIC-GRUJICIC, S. 2008. Anti-tumor effect of Coriolus Versicolor
methanol extract against mouse B16 melanoma cells: in vitro and in vivo study. Food and
Chemical Toxicology, 46, 1825-1833.
HATVANI, N. 2001. Antibacterial effect of the culture fluid of Lentinus edodes mycelium grown in
submerged liquid culture. International Journal of Antimicrobial Agents, 17, 71-74.
HAZEKAWA, M., KATAOKA, A., HAYAKAWA, K., UCHIMASU, T., FURUTA, R., IRIE, K.,
AKITAKE, Y., YOSHIDA, M., FUJIOKA, T., EGASHIRA, N., OISHI, R., MISHIMA, K.,
UCHIDA, T., IWASAKI, K. & FUJIWARA, M. 2010. Neuroprotective Effect of Repeated
Treatment with Hericium erinaceum in Mice Subjected to Middle Cerebral Artery Occlusion.
Journal of Health Science, 56, 296-303.
HEARST, R., NELSON, D., MCCOLLUM, G., MILLAR, B. C., MAEDA, Y., GOLDSMITH, C. E.,
ROONEY, P. J., LOUGHREY, A., RAO, J. R. & MOORE, J. E. 2009a. An examination of
antibacterial and antifungal properties of constituents of Shiitake (Lentinula edodes) and
oyster (Pleurotus ostreatus) mushrooms. Complementary Therapies in Clinical Practice,
15, 5-7.
HEARST, R., NELSON, D., MCCOLLUM, G., MILLAR, B. C., MAEDA, Y., GOLDSMITH, C. E.,
ROONEY, P. J., LOUGHREY, A., RAO, J. R. & MOORE, J. E. 2009b. An examination of
antibacterial and antifungal properties of constituents of Shiitake (Lentinula edodes) and
oyster (Pleurotus ostreatus) mushrooms. Complement Ther Clin Pract, 15, 5-7.
HETLAND, G., JOHNSON, E., LYBERG, T., BERNARDSHAW, S., TRYGGESTAD, A. M. A. &
GRINDE, B. 2008. Effects of the medicinal mushroom Agaricus Blazei Murill on immunity,
infection and cancer. Scandinavian Journal of Immunology, 68, 363-370.
HETLAND, G., JOHNSON, E., LYBERG, T. & KVALHEIM, G. 2011. The mushroom Agaricus
blazei Murill elicits medicinal effects on tumor, infection, allergy, and inflammation through
Its modulation of innate immunity and amelioration of Th1/Th2 imbalance and
inflammation. Advances in Pharmacological Sciences, 2011, Article 157015.
HIRAMOTO, K., KAKU, M., KATO, T. & KIKUGAWA, K. 1995. DNA strand breaking by the carboncentered radical generated from 4-(hydroxymethyl) benzenediazonium salt, a carcinogen in
mushroom Agaricus bisporus. Chemico-Biological Interactions, 94, 21-36.
HIRASAWA, M., SHOUJI, N., NETA, T., FUKUSHIMA, K. & TAKADA, K. 1999. Three kinds of
antibacterial substances from Lentinus edodes (Berk.) Sing. (Shiitake, an edible
mushroom). International Journal of Antimicrobial Agents, 11, 151-157.
HIWATASHI, K., KOSAKA, Y., SUZUKI, N., HATA, K., MUKAIYAMA, T., SAKAMOTO, K.,
SHIRAKAWA, H. & KOMAI, M. 2010. Yamabushitake mushroom (Hericium erinaceus)
improved lipid metabolism in mice fed a high-fat diet. Bioscience, Biotechnology, and
HONG, J. H., KIM, S. J., RAVINDRA, P. & YOUN, K. S. 2007. Antitumor activities of spray-dried
powders with different molecular masses fractionated from the crude protein-bound
polysaccharide extract of Agaricus Blazei Murill. Food Science and Biotechnology, 16, 600604.
HONG, K. J., DUNN, D. M., SHEN, C. L. & PENCE, B. C. 2004. Effects of Ganoderma lucidum on
apoptotic and anti-inflammatory function in HT-29 human colonic carcinoma cells.
Phytotherapy Research, 18, 768-770.
316
HONG, S. A., KIM, K., NAM, S. J., KONG, G. & KIM, M. K. 2008. A case-control study on the
dietary intake of mushrooms and breast cancer risk among Korean women. International
Journal of Cancer, 122, 919-23.
HOR, S. Y., AHMAD, M., FARSI, E., LIM, C. P., ASMAWI, M. Z. & YAM, M. F. 2011. Acute and
subchronic oral toxicity of Coriolus versicolor standardized water extract in SpragueDawley rats. Journal of Ethnopharmacology, 137, 1067-1076.
HOSSAIN, S., HASHIMOTO, M., CHOUDHURY, E. K., ALAM, N., HUSSAIN, S., HASAN, M.,
CHOUDHURY, S. K. & MAHMUD, I. 2003. Dietary mushroom (Pleurotus ostreatus)
ameliorates atherogenic lipid in hypercholesterolaemic rats. Clinical and Experimental
Pharmacology and Physiology, 30, 470-465.
HSIEH, T. C. & WU, J. M. 2011. Suppression of proliferation and oxidative stress by extracts of
Ganoderma lucidum in the ovarian cancer cell line OVCAR-3. International Journal of
Molecular Medicine, 28, 1065-1069.
HSU, C.-H., LIAO, Y.-L., LIN, S.-C., HWANG, K.-C. & CHOU, P. 2007. The mushroom Agaricus
blazei Murill in combination with metformin and gliclazide improves insulin resistance in
type 2 diabetes: A randomized, double-blinded, and placebo-controlled clinical trial. Journal
of Alternative and Complementary Medicine, 13, 97-102.
HSU, C. H., HWANG, H. J., CHIANG, Y. H. & CHOU, P. 2008a. The mushroom Agaricus blazei
Murill extract normalizes liver function in patients with chronic hepatitis B. Journal of
Alternative and Complementary Medicine, 14, 299-301.
HSU, C. L., YU, Y. S. & YEN, G. C. 2008b. Lucidenic acid B induces apoptosis in human leukemia
cells via a mitochondria-mediated pathway. Journal of Agricultural and Food Chemistry, 56,
3973-3980.
HSU, J. W., HUANG, H. C., CHEN, S. T., WONG, C. H. & JUAN, H. F. 2009. Ganoderma lucidum
Polysaccharides Induce Macrophage-like Differentiation in Human Leukemia THP-1 Cells
via Caspase and p53 Activation. Evid Based Complement Alternat Med.
HUANG, C. H., TSAI, H. N., PENG, R. H., HSIEH, Y. H., CHUANG, W. J., HSU, G. C., HUANG, W.
Y. & CHEN, W. J. 2010a. Agaricus Blazei Murill ameliorates myocardial ischemiareperfusion injury. Acta Cardiologica Sinica, 26, 235-241.
HUANG, G., DENG, J., HUANG, S. & HU, M. 2011. Hispolon induces apoptosis and cell cycle
arrest of human hepatocellular carcinoma Hep3B cells by modulating ERK
phosphorylation. Journal of Agricultural and Food Chemistry, 59, 7104-7113.
HUANG, G., YANG, C., CHANG, Y., AMAGAYA, S., WANG, H., HOU, W., HUANG, S. & HU, M.
2010b. Hispolon suppresses SK-Hep1 human hepatoma cell metastasis by inhibiting
matrix metalloproteinase-2/9 and urokinase-plasminogen activator through the PI3K/Akt
and ERK signaling pathways. Journal of Agricultural and Food Chemistry, 58, 9468-9475.
HWANG, H. S., LEE, S. H., BAEK, Y. M., KIM, S. W., JEONG, Y. K. & YUN, J. W. 2008.
Production of extracellular polysaccharides by submerged mycelial culture of Laetiporus
sulphureus var. miniatus and their insulinotropic properties. Applied Microbiology and
Biotechnology, 78, 419-429.
HWANG, H. S. & YUN, J. W. 2010. Hypoglycemic effect of polysaccharides produced by
submerged mycelial culture of Laetiporus sulphureus on streptozotocin-induced diabetic
rats. Biotechnology and Bioprocess Engineering, 15, 173-181.
HYE-JIN, H., BAEK, Y. M., KIM, S. W., KUMAR, G. S., CHO, E. J., OH, J. Y. & YUN, J. W. 2007.
Differential Expression of Kidney Proteins in Streptozotocin-Induced Diabetic Rats in
Response to Hypoglycemic Fungal Polysaccharides. Journal of Microbiology and
317
HYUN JI, P., YONG, H. & JONG BONG, K. 2011. Immunomodulating effect of edible mushrooms
in mice. Korean Journal of Life Science, 21, 515-520.
HYUNG SOOK, K., JEE YOUN, K., JONG SOON, K., HWAN MOOK, K., YONG OOK, K., IN PYO,
H., MI KYEONG, L., JIN TAE, H., YOUNGSOO, K. & SANG-BAE, H. 2010. Cordlan
polysaccharide isolated from mushroom Cordyceps militaris induces dendritic cell
maturation through toll-like receptor 4 signalings. Food and Chemical Toxicology, 48,
1926-1933.
ICHINOHE, T., AINAI, A., NAKAMURA, T., AKIYAMA, Y., MAEYAMA, J., ODAGIRI, T., TASHIRO,
M., TAKAHASHI, H., SAWA, H., TAMURA, S., CHIBA, J., KURATA, T., SATA, T. &
HASEGAWA, H. 2010. Induction of cross-protective immunity against influenza A virus
H5N1 by an intranasal vaccine with extracts of mushroom mycelia. Journal of Medical
Virology, 82, 128-137.
IKEKAWA, T., IKEDA, Y., YOSHIOKA, Y., NAKANISHI, K., YOKOYAMA, E. & YAMAZAKI, E.
1982. Studies on antitumor polysaccharides of Flammulina velutipes (Curt. ex Fr.) Sing.II.
The structure of EA3 and further purification of EA5. Journal of Pharmaco-biodynamics, 5,
576-581.
IKEKAWA, T., MARUYAMA, H., MIYANO, T., OKURA, A., SAWASAKI, Y., NAITO, K.,
KAWAMURA, K. & SHIRATORI, K. 1985. Proflamin, a new antitumor agent: preparation,
physicochemical properties and antitumor activity. Japanese Journal of Cancer Research,
76, 142-148.
IKEKAWA, T., SAITOH, H., FENG, W., ZHANG, H., LI, L. & MATSUZAWA, T. 1992. Antitumor
activity of Hypsizigus marmoreus. I. Antitumor activity of extracts and polysaccharides.
Chemical and Pharmaceutical Bulletin (Tokyo), 40, 1954-1957.
INAGAKI, N., SHIBATA, T., ITOH, T., SUZUKI, T., TANAKA, H., NAKAMURA, T., AKIYAMA, Y.,
KAWAGISHI, H. & NAGAI, H. 2005. Inhibition of IgE-dependent mouse triphasic cutaneous
reaction by a boiling water fraction separated from mycelium of Phellinus linteus. EvidenceBased Complementary and Alternative Medicine, 2, 369-374.
INAGE, M., TAKAHASHI, H., NAKAMURA, H., MASAKANE, I. & TOMOIKE, H. 1996.
Hypersensitivity pneumonitis induced by spores of Pholiota nameko. Internal Medicine, 35,
301-304.
INOUE, A., KODAMA, N. & NANBA, H. 2002. Effect of maitake (Grifola frondosa) D-fraction on the
control of the T lymph node Th-1/Th-2 proportion. Biological and Pharmaceutical Bulletin,
25, 536-540.
INUZUKA, H. & YOSHIDA, T. 2002. Clinical utility of ABCL (Agaricus Mushroom Extract) treatment
for C-type hepatitis. Japanese Pharmacology and Therapeutics, 30, 103-107.
ISAI, M., ELANCHEZHIAN, R., SAKTHIVEL, M., CHINNAKKARUPPAN, A., RAJAMOHAN, M.,
JESUDASAN, C. N., THOMAS, P. A. & GERALDINE, P. 2009. Anticataractogenic effect of
an extract of the oyster mushroom, Pleurotus ostreatus, in an experimental animal model.
Current Eye Research, 34, 264-73.
ISHIBASHI, K., YOSHIDA, M., NAKABAYASHI, I., YOSHIKAWA, N., MIURA, N. N., ADACHI, Y. &
OHNO, N. 2011. Characterization of blood beta-1,3-glucan and anti-beta-glucan antibody
in hemodialysis patients using culinary-medicinal Royal Sun Agaricus, Agaricus brasiliensis
S. Wasser et al. (Agaricomycetideae). International Journal of Medicinal Mushrooms, 13,
101-107.
ISHII, P. L., KATO PRADO, C., OLIVEIRA MAURO, M. D., CARREIRA, C. M., MANTOVANI, M.
S., RIBEIRO, L. R., BANDEIRA DICHI, J. & OLIVEIRA, R. J. 2011. Evaluation of Agaricus
blazei in vivo for antigenotoxic, anticarcinogenic, phagocytic and immunomodulatory
activities. Regulatory Toxicology and Pharmacology, 59, 412-422.
318
ISHIKAWA, N. K., FUKUSHI, Y., YAMAJI, K., TAHARA, S. & TAKAHASHI, K. 2001. Antimicrobial
cuparene-type sesquiterpenes, enokipodins C and D, from a mycelial culture of
Flammulina velutipes. J Nat Prod, 64, 932-934.
ISRAILIDES, C., KLETSAS, D., ARAPOGLOU, D., PHILIPPOUSSIS, A., PRATSINIS, H.,
EBRINGEROVA, A., HRIBALOVA, V. & HARDING, S. E. 2008. In vitro cytostatic and
immunomodulatory properties of the medicinal mushroom Lentinula edodes.
Phytomedicine, 15, 512-519.
ITO, T., KATO, M., TSUCHIDA, H., HARADA, E., NIWA, T. & OSAWA, T. 2011. Ergothioneine as
an anti-oxidative/anti-inflammatory component in several edible mushrooms. Food Science
and Technology Research, 17, 103-110.
ITOH, A., ISODA, K., KONDOH, M., KAWASE, M., WATARI, A., KOBAYASHI, M., TAMESADA, M.
& YAGI, K. 2010. Hepatoprotective effect of syringic acid and vanillic acid on CCl 4induced liver injury. Biological & Pharmaceutical Bulletin, 33, 983-987.
ITOH, H., ITO, H. & HIBASAMI, H. 2008. Blazein of a new steroid isolated from Agaricus blazei
Murrill (himematsutake) induces cell death and morphological change indicative of
apoptotic chromatin condensation in human lung cancer LU99 and stomach cancer KATO
III cells. Oncology Reports, 20, 1359-61.
IZAWA, S. & INOUE, Y. 2004. A screening system for antioxidants using thioredoxin-deficient
yeast: Discovery of thermostable antioxidant activity from Agaricus blazei Murill. Applied
Microbiology and Biotechnology, 64, 537-542.
JAGADISH, L. K., KRISHNAN, V. V., SHENBHAGARAMAN, R. & KAVIYARASAN, V. 2009.
Comparitive study on the antioxidant, anticancer and antimicrobial property of Agaricus
bisporus (J. E. Lange) imbach before and after boiling. African Journal of Biotechnology, 8,
654-661.
JAN-YING, Y., LI-HUI, H., KAUN-TZER, W. & CHENG-FANG, T. 2011. Antioxidant properties and
antioxidant compounds of various extracts from the edible basidiomycete Grifola frondosa
(Maitake). Molecules, 16, 3197-3211.
JANG, J., LEE, J., LEE, J., KWON, D., LEE, K., LEE, S. & HONG, E. 2010a. Hispidin produced
from Phellinus linteus protects pancreatic beta-cells from damage by hydrogen peroxide.
Archives of Pharmacal Research, 33, 853-861.
JANG, J. H., JEONG, S. C., KIM, J. H., LEE, Y. H., JU, Y. C. & LEE, J. S. 2011a. Characterisation
of a new antihypertensive angiotensin I-converting enzyme inhibitory peptide from
Pleurotus cornucopiae. Food Chemistry, 127, 412-418.
JANG, K. J., HAN, M. H., LEE, B. H., KIM, B. W., KIM, C. H., YOON, H. M. & CHOI, Y. H. 2010b.
Induction of apoptosis by ethanol extracts of Ganoderma lucidum in human gastric
carcinoma cells. J Acupunct Meridian Stud, 3, 24-31.
JANG, S. A., KANG, S. C. & SOHN, E. H. 2011b. Phagocytic effects of beta-glucans from the
mushroom Coriolus versicolor are related to dectin-1, NOS, TNF-alpha signaling in
macrophages. Biomolecules & Therapeutics, 19, 438-444.
JASINGHE, V. J. & PERERA, C. O. 2006. Ultraviolet irradiation: the generator of vitamin D-2 in
edible mushrooms. Food Chemistry, 95, 638-643.
JASINGHE, V. J., PERERA, C. O. & BARLOW, P. J. 2005. Bioavailability of vitamin D2 from
irradiated mushrooms: an in vivo study. British Journal of Nutrition, 93, 951-955.
JAYAKUMAR, T., THOMAS, P. A., ISAI, M. & GERALDINE, P. 2010a. An extract of the oyster
mushroom, Pleurotus ostreatus, increases catalase gene expression and reduces protein
oxidation during aging in rats. Zhong Xi Yi Jie He Xue Bao, 8, 774-80.
319
JAYAKUMAR, T., THOMAS, P. A., RAMESH, E. & GERALDINE, P. 2010b. An extract of the
Pleurotus ostreatus mushroom bolsters the glutathione redox system in various organs of
aged rats. Journal of Medicinal Food, 13, 771-778.
JAYAKUMAR, T., THOMAS, P. A., SHEU, J. R. & GERALDINE, P. 2011. In-vitro and in-vivo
antioxidant effects of the oyster mushroom Pleurotus ostreatus. Food Research
International, 44, 851-861.
JEDINAK, A., DUDHGAONKAR, S., JIANG, J. H., SANDUSKY, G. & SLIVA, D. 2010. Pleurotus
ostreatus inhibits colitis-related colon carcinogenesis in mice. International Journal of
Molecular Medicine, 26, 643-650.
JEDINAK, A., DUDHGAONKAR, S., WU, Q. L., SIMON, J. & SLIVA, D. 2011a. Anti-inflammatory
activity of edible oyster mushroom is mediated through the inhibition of NF-kappaB and
AP-1 signaling. Nutrition Journal, 10, (16 May 2011).
JEDINAK, A. & SLIVA, D. 2008. Pleurotus ostreatus inhibits proliferation of human breast and
colon cancer cells through p53-dependent as well as p53-independent pathway.
International Journal of Oncology, 33, 1307-1313.
JEDINAK, A., THYAGARAJAN-SAHU, A., JIANG, J. H. & SLIVA, D. 2011b. Ganodermanontriol, a
lanostanoid triterpene from Ganoderma lucidum, suppresses growth of colon cancer cells
through beta-catenin signaling. International Journal of Oncology, 38, 761-767.
JEONG, S., JEONG, Y., YANG, B., ISLAM, R., KOYYALAMUDI, S. R., PANG, G., CHO, K. &
SONG, C. 2010. White button mushroom (Agaricus bisporus) lowers blood glucose and
cholesterol levels in diabetic and hypercholesterolemic rats. Nutrition Research, 30, 49-56.
JEONG, S. C., KOYYALAMUDI, S. R., JEONG, Y. T., SONG, C. H. & PANG, G. 2012.
Macrophage immunomodulating and antitumor activities of polysaccharides isolated from
Agaricus bisporus white button mushrooms. Journal of Medicinal Food, 15, 58-65.
JEONG, S. C., KOYYALAMUDI, S. R. & PANG, G. 2011. Dietary intake of Agaricus bisporus white
button mushroom accelerates salivary immunoglobulin A secretion in healthy volunteers.
Nutrition.
JEURINK, P. V., NOGUERA, C. L., SAVELKOUL, H. F. J. & WICHERS, H. J. 2008.
Immunomodulatory capacity of fungal proteins on the cytokine production of human
peripheral blood mononuclear cells. International Immunopharmacology, 8, 1124-1133.
JI, Z., TANG, Q. J., ZHANG, J. S., YANG, Y., LIU, Y. F. & PAN, Y. J. 2011. Immunomodulation of
bone marrow macrophages by GLIS, a proteoglycan fraction from Lingzhi or Reishi
medicinal mushroom Ganoderma lucidium (W.Curt.: Fr.) P. Karst. International Journal of
JIA, J., ZHANG, X., HU, Y., WU, Y., WANG, Q., LI, N., GUO, Q. & DONG, X. 2009. Evaluation of in
vivo antioxidant activities of Ganoderma lucidum polysaccharides in STZ-diabetic rats.
Food Chemistry, 115, 32-36.
JIANG, J., SLIVOVA, V., HARVEY, K., VALACHOVICOVA, T. & SLIVA, D. 2004a. Ganoderma
lucidum suppresses growth of breast cancer cells through the inhibition of Akt/NF-kappaB
signaling. Nutrition and Cancer, 49, 209-216.
JIANG, J., SLIVOVA, V. & SLIVA, D. 2006. Ganoderma lucidum inhibits proliferation of human
breast cancer cells by down-regulation of estrogen receptor and NF-kappaB signaling.
JIANG, J., SLIVOVA, V., VALACHOVICOVA, T., HARVEY, K. & SLIVA, D. 2004b. Ganoderma
lucidum inhibits proliferation and induces apoptosis in human prostate cancer cells PC-3.
320
JIANG, J. H., GRIEB, B., THYAGARAJAN, A. & SLIVA, D. 2008. Ganoderic acids suppress growth
and invasive behavior of breast cancer cells by modulating Ap-1 and Nf-Kappa B signaling.
International Journal of Molecular Medicine, 21, 577-584.
JIANG, J. H., JEDINAK, A. & SLIVA, D. 2011a. Ganodermanontriol (GDNT) exerts its effect on
growth and invasiveness of breast cancer cells through the down-regulation of CDC20 and
uPA. Biochemical and Biophysical Research Communications, 415, 325-329.
JIANG, S., CHEN, Y., WANG, M., YIN, Y., PAN, Y., GU, B., YU, G., LI, Y., WONG, B., LIANG, Y. &
SUN, H. 2012. A novel lectin from Agrocybe aegerita shows high binding selectivity for
terminal N-acetylglucosamine. Biochem J.
JIANG, Y., WONG, J. H., FU, M., NG, T. B., LIU, Z. K., WANG, C. R., LI, N., QIAO, W. T., WEN, T.
Y. & LIU, F. 2011b. Isolation of adenosine, iso-sinensetin and dimethylguanosine with
antioxidant and HIV-1 protease inhibiting activities from fruiting bodies of Cordyceps
militaris. Phytomedicine, 18, 189-193.
JIN, C. Y., CHOI, Y. H., MOON, D. O., PARK, C., PARK, Y. M., JEONG, S. C., HEO, M. S., LEE,
T. H., LEE, J. D. & KIM, G. Y. 2006. Induction of G2/M arrest and apoptosis in human
gastric epithelial AGS cells by aqueous extract of Agaricus blazei. Oncology Reports, 16,
1349-1355.
JIN, C. Y., KIM, G. Y. & CHOI, Y. H. 2008. Induction of apoptosis by aqueous extract of Cordyceps
militaris through activation of caspases and inactivation of Akt in human breast cancer
MDA-MB-231 Cells. Journal of Microbiology and Biotechnology, 18, 1997-2003.
JIN, C. Y., MOON, D. O., CHOI, Y. H., LEE, J. D. & KIM, G. Y. 2007. Bcl-2 and caspase-3 are
major regulators in Agaricus blazei-induced human leukemic U937 cell apoptosis through
dephoshorylation of Akt. Biological and Pharmaceutical Bulletin, 30, 1432-1437.
JOHNSON, E., FORLAND, D. T., SAETRE, L., BERNARDSHAW, S. V., LYBERG, T. & HETLAND,
G. 2009. Effect of an extract based on the medicinal mushroom Agaricus blazei murill on
release of cytokines, chemokines and leukocyte growth factors in human blood ex vivo and
in vivo. Scandinavian Journal of Immunology, 69, 242-250.
JOSEPH, J., PANICKER, S. N. & JANARDHANAN, K. K. 2012. Protective effect of polysaccharideprotein complex from a polypore mushroom, Phellinus rimosus against radiation-induced
oxidative stress. Redox Report, 17, 14-19.
JOSEPH, J., SMINA, T. P. P. & JANARDHANAN, K. K. 2011. Polysaccharide protein complex
isolated from mushroom Phellinus rimosus (Berk.) Pilat alleviates gamma radiationinduced toxicity in mice. Cancer Biotherapy & Radiopharmaceuticals, 26, 299-308.
JUNG-IN, K., MIN-JUNG, K., JIEUN, I., YEONG-JU, S., YOUNG-MIN, L., JI-HYUN, S., JAI-HEON,
L. & MI-EUN, K. 2010. Effect of king oyster mushroom ( Pleurotus eryngii) on insulin
resistance and dyslipidemia in db/ db mice. Food Science and Biotechnology, 19, 239-242.
JUNG, J. Y., LEE, I. K., SEOK, S. J., LEE, H. J., KIM, Y. H. & YUN, B. S. 2008. Antioxidant
polyphenols from the mycelial culture of the medicinal fungi Inonotus Xeranticus and
Phellinus Linteus. Journal of Applied Microbiology, 104, 1824-1832.
KABIR, Y. & KIMURA, S. 1989. Dietary mushrooms reduce blood pressure in spontaneously
hypertensive rats (SHR). Journal of Nutritional Science and Vitaminology (Tokyo), 35, 9194.
KAI, N., ISHII, H., IWATA, A., UMEKI, K., SHIRAI, R., MORINAGA, R., KISHI, K., TOKIMATSU, I.,
HIRAMATSU, K., YAMAGATA, E. & KADOTA, J. 2008. Chronic hypersensitivity
pneumonitis induced by Shiitake mushroom cultivation: case report and review of literature.
Nihon Kokyuki Gakkai Zasshi - Jounal of the Japanese Respiratory Society, 46, 411-415.
321
KANAYA, N., KUBO, M., LIU, Z., CHU, P., WANG, C. & CHEN, Y.-C. Y. S. 2011a. Protective
Effects of White Button Mushroom (Agaricus bisporus) against Hepatic Steatosis in
Ovariectomized Mice as a Model of Postmenopausal Women. PLoS One, 6, e26654.
KANAYA, N., KUBO, M., ZHENG, L., PEIGUO, C., WANG, C., YATE-CHING, Y. & SHIUAN, C.
2011b. Protective effects of white button mushroom (Agaricus bisporus) against hepatic
steatosis in ovariectomized mice as a model of postmenopausal women. PLoS ONE, 6,
e26654.
KAWAGISHI, H. 2007. Anti-dementia compounds from the mushroom Hericium Erinaceum. Drugs
of the Future, 32, 17-18.
KAWAGISHI, H. & ZHUANG, C. 2008. Compounds for dementia from Hericium erinaceum. Drugs
of the Future, 33, 149-155.
KHAMAISIE, H., SUSSAN, S., TAL, I., NAJAJREH, O., RUTHARDT, M. & MAHAJNA, J. 2011.
Oleic acid is the active component in the mushroom Daedalea gibbosa inhibiting Bcr-Abl
kinase autophosphorylation activity. Anticancer Research, 31, 177-183.
KHATUN, K., MAHTAB, H., KHANAM, P. A., SAYEED, M. A. & KHAN, K. A. 2007. Oyster
mushroom reduced blood glucose and cholesterol in diabetic subjects. Mymensingh
Medical Journal, 16, 94-99.
KIHO, T., IGUCHI, K., USUI, S. & HIRANO, K. 2010. Effect of polysaccharides and 70% ethanol
extracts from medicinal mushrooms on growth of human prostate cancer LNCaP and PC-3
cells. International Journal of Medicinal Mushrooms, 12, 205-211.
KIM, B.-C., CHOI, J.-W., HONG, H.-Y., LEE, S.-A., HONG, S., PARK, E.-H., KIM, S.-J. & LIM, C.-J.
2006a. Heme oxygenase-1 mediates the anti-inflammatory effect of mushroom Phellinus
linteus in LPS-stimulated RAW264.7 macrophages. Journal of Ethnopharmacology, 106,
364-371.
KIM, C., JIANG, J., LEUNG, K., FUNG, K. & LAU, B. 2009a. Inhibitory effects of Agaricus blazei
extracts on human myeloid leukemia cells. Journal of Ethnopharmacology, 122, 320-326.
KIM, D. H., JANG, I. S., PARK, J. B. & LEE, S. W. 1995. Protective roles of mushrooms in
experimental colon carcinogenesis. Archives of Pharmacology Research, 18, 79-83.
KIM, D. H., YANG, B. K., JEONG, S. C., HUR, N. J., DAS, S., YUN, J. W., CHOI, J. W., LEE, Y. S.
& SONG, C. H. 2001. A preliminary study on the hypoglycemic effect of the exo-polymers
produced by five different medicinal mushrooms. Journal of Microbiology and
KIM, H., KIM, J., KANG, J., KIM, H., KIM, Y., HONG, I., LEE, M., HONG, J., KIM, Y. & HAN, S.
2010a. Cordlan polysaccharide isolated from mushroom Cordyceps militaris induces
dendritic cell maturation through toll-like receptor 4 signalings. Food and Chemical
Toxicology, 48, 1926-1933.
KIM, H., KIM, J., RYU, H., PARK, H., KIM, Y., KANG, J., KIM, H., HONG, J., KIM, Y. & HAN, S.
2010b. Induction of dendritic cell maturation by beta-glucan isolated from Sparassis crispa.
International Immunopharmacology, 10, 1284-1294.
KIM, H. G., YOON, D. H., LEE, W. H., HAN, S. K., SHRESTHA, B., KIM, C. H., LIM, M. H.,
CHANG, W., LIM, S., CHOI, S., SONG, W. O., SUNG, J. M., HWANG, K. C. & KIM, T. W.
2007a. Phellinus linteus inhibits inflammatory mediators by suppressing redox-based NF?B and MAPKs activation in lipopolysaccharide-induced RAW 264.7 macrophage. Journal
of Ethnopharmacology, 114, 307-315.
KIM, H. G., YOON, D. H., LEE, W. H., HAN, S. K., SHRESTHA, B., KIM, C. H., LIM, M. H.,
CHANG, W., LIM, S., CHOI, S., SONG, W. O., SUNG, J. M., HWANG, K. C. & KIM, T. W.
322
2007b. Phellinus Linteus inhibits inflammatory mediators by suppressing redox-based NfKappa B and MAPKs activation in lipopolysaccharide-induced Raw 264.7 macrophage.
Journal of Ethnopharmacology, 114, 307-315.
KIM, H. M., KANG, J. S., KIM, J. Y., PARK, S. K., KIM, H. S., LEE, Y. J., YUN, J., HONG, J. T.,
KIM, Y. & HAN, S. B. 2010c. Evaluation of antidiabetic activity of polysaccharide isolated
from Phellinus linteus in non-obese diabetic mouse. International Immunopharmacology,
10, 72-78.
KIM, J. I., KANG, M. J., IM, J., SEO, Y. J., LEE, Y. M., SONG, J. H., LEE, J. H. & KIM, M. E.
2010d. Effect of King Oyster Mushroom (Pleurotus eryngii) on insulin resistance and
dyslipidemia in db/db mice. Food Science and Biotechnology, 19, 239-242.
KIM, J. M., RA, K. S., NOH, D. O. & SUH, H. J. 2002. Optimization of submerged culture conditions
for the production of angiotensin converting enzyme inhibitor from Flammulina velutipes.
Journal of Industrial Microbiology and Biotechnology, 29, 292-295.
KIM, K. C. & KIM, I. G. 1999. Ganoderma lucidum extract protects DNA from strand breakage
caused by hydroxyl radical and UV irradiation. International Journal of Molecular Medicine,
4, 273-277.
KIM, M. Y., CHUNG, I. M., LEE, S. J., AHN, J. K., KIM, E. H., KIM, M. J., KIM, S. L., MOON, H. I.,
RO, H. M., KANG, E. Y., SEO, S. H. & SONG, H. K. 2009b. Comparison of free amino
acid, carbohydrates concentrations in Korean edible and medicinal mushrooms. Food
Chemistry, 113, 386-393.
KIM, M. Y., SEGUIN, P., AHN, J. K., KIM, J. J., CHUN, S. C., KIM, E. H., SEO, S. H., KANG, E. Y.,
KIM, S. L., PARK, Y. J., RO, H. M. & CHUNG, I. M. 2008. Phenolic compound
concentration and antioxidant activities of edible and medicinal mushrooms from Korea.
KIM, S.-H., SONG, Y.-S., KIM, S.-K., KIM, B.-C., LIM, C.-J. & PARK, E.-H. 2004a. Antiinflammatory and related pharmacological activities of the n-BuOH subfraction of
mushroom Phellinus linteus. Journal of Ethnopharmacology, 93, 141-146.
KIM, S., KANG, M., CHOI, Y., KIM, J., NAM, S. & FRIEDMAN, M. 2011a. Mechanism of Hericium
erinaceus (Yamabushitake) mushroom-induced apoptosis of U937 human monocytic
leukemia cells. Food and Function, 2, 348-356.
KIM, S., KANG, M., KIM, J., NAM, S. & FRIEDMAN, M. 2011b. Composition and mechanism of
antitumor effects of Hericium erinaceus mushroom extracts in tumor-bearing mice. Journal
of Agricultural and Food Chemistry, 59, 9861-9869.
KIM, S. W., KIM, H. G., LEE, B. E., HWANG, H. H., BAEK, D. H. & KO, S. Y. 2006b. Effects of
mushroom, Pleurotus eryngii, extracts on bone metabolism. Clinical Nutrition, 25, 166-170.
KIM, T. I., PARK, S. J., CHOI, C. H., LEE, S. K. & KIM, W. H. 2004b. Effect of ear mushroom
(Auricularia) on functional constipation. Korean Journal of Gastroenterology, 44, 34-41.
KIM, Y. W., KIM, K. H., CHOI, H. J. & LEE, D. S. 2005. Anti-diabetic activity of beta-glucans and
their enzymatically hydrolyzed oligosaccharides from Agaricus blazei. Biotechnology
Letters, 27, 483-487.
KIMURA, C., NUKINA, M., IGARASHI, K. & SUGAWARA, Y. 2005. beta-Hydroxyergothioneine, a
new ergothioneine derivative from the mushroom Lyophyllum connatum, and its protective
activity against carbon tetrachloride-induced injury in primary culture hepatocytes.
Bioscience Biotechnology and Biochemistry, 69, 357-363.
323
KIMURA, Y., KIDO, T., TAKAKU, T., SUMIYOSHI, M. & BABA, K. 2004. Isolation of an antiangiogenic substance from Agaricus blazei Murill: its antitumor and antimetastatic actions.
Cancer Science, 95, 758-764.
KO, J. A., PARK, H. J., LEE, B. H. & LEE, J. S. 2008. Effect of UV-B exposure on the concentration
of vitamin D2 in sliced Shiitake mushroom (Lentinus Edodes) and white button mushroom
(Agaricus Bisporus). Journal of Agricultural and Food Chemistry, 56, 3671-3674.
KO, J. L., HSU, C. I., LIN, R. H., KAO, C. L. & LIN, J. Y. 1995. A new fungal immunomodulatory
protein, FIP-fve isolated from the edible mushroom, Flammulina velutipes and its complete
amino acid sequence. European Journal of Biochemistry, 228, 244-249.
KOBORI, M., YOSHIDA, M., OHNISHI-KAMEYAMA, M. & SHINMOTO, H. 2007. Ergosterol
peroxide from an edible mushroom suppresses inflammatory responses in RAW264.7
macrophages and growth of HT29 colon adenocarcinoma cells. British Journal of
Pharmacology, 150, 209-219.
KODAMA, N., KAKUNO, T. & NANBA, H. 2003. Stimulation of the natural immune system in
normal mice by polysaccharide from Maitake mushroom. Mycoscience, 44, 257-261.
KODAMA, N., MIZUNO, S., NANBA, H. & SAITO, N. 2010. Potential antitumor activity of a lowmolecular-weight protein fraction from Grifola frondosa through enhancement of cytokine
production. Journal of Medicinal Food, 13, 20-30.
KOH, J. H., KIM, J. M., CHANG, U. J. & SUH, H. J. 2003. Hypocholesterolemic effect of hot-water
extract from mycelia of Cordyceps Sinensis. Biological & Pharmaceutical Bulletin, 26, 8487.
KOHNO, K., MIYAKE, M., SANO, O., TANAKA-KATAOKA, M., YAMAMOTO, S., KOYA-MIYATA,
S., ARAI, N., FUJII, M., WATANABE, H., USHIO, S., IWAKI, K. & FUKUDA, S. 2008. Antiinflammatory and immunomodulatory properties of 2-amino-3H-phenoxazin-3-one.
Biological and Pharmaceutical Bulletin, 31, 1938-1945.
KOIKE, T., IHOTA, H., FUJIMURA, T., KIMURA, H., OKADA, M., HASEGAWA, K. & NAGAOKA,
H. 2002a. Single dose toxicity study of extract of cultured Lentinus Edodes Mycelia by oral
administration in rats. Pharmacometrics, 62, 1-3.
KOIKE, T., IHOTA, H., NAGASE, T., KIMURA, H., OKADA, M., HASEGAWA, K. & NAGAOKA, H.
2002b. Repeated dose toxicity study of extract of cultured Lentinus Edodes Mycelia by 28day oral administration in rats. Pharmacometrics, 62, 5-12.
KOIKE, T., NAGASE, T., FUJIMURA, T., OKADA, M., SHIMIZU, M., SHIMIZU, A. & HASEGAWA,
K. 2003. Single dose toxicity study of powdered Grifola Frondosa by oral administration in
rats. Pharmacometrics, 65, 39-41.
KONDO, K., WATANABE, A., AKIYAMA, H. & MAITANI, T. 2008. The metabolisms of agaritine, a
mushroom hydrazine in mice. Food and Chemical Toxicology, 46, 854-862.
KOO, K.-C., LEE, D.-H., KIM, J.-H., YU, H.-E., PARK, J.-S. & LEE, J.-S. 2006. Production and
characterization of antihypertensive angiotensin I-converting enzyme inhibitor from
Pholiota adiposa. Journal of Microbiology and Biotechnology, 16, 757-763.
KOYYALAMUDI, S. R., JEONG, S. C., CHO, K. Y. & PANG, G. 2009a. Vitamin B12 is the active
corrinoid produced in cultivated white button mushrooms (Agaricus bisporus). J Agric Food
Chem, 57, 6327-33.
KOYYALAMUDI, S. R., JEONG, S. C., SONG, C. H., CHO, K. Y. & PANG, G. 2009b. Vitamin D2
formation and bioavailability from Agaricus bisporus button mushrooms treated with
ultraviolet irradiation. J Agric Food Chem, 57, 3351-5.
324
KRISTENSEN, H. L., ROSENQVIST, E. & JAKOBSEN, J. 2012. Increase of vitamin D(2) by UV-B
exposure during the growth phase of white button mushroom (Agaricus bisporus). Food
Nutr Res, 56, 7114.
KUBO, K. & NANBA, H. 1996. The effect of maitake mushrooms on liver and serum lipids.
Alternative Therapies in Health and Medicine, 2, 62-66.
KUBO, K. & NANBA, H. 1997. Anti-hyperliposis effect of Maitake fruit body (Grifola Frondosa) .1.
Biological & Pharmaceutical Bulletin, 20, 781-785.
KUO, M. C., WENG, C. Y., HA, C. L. & WU, M. J. 2006. Ganoderma lucidum mycelia enhance
innate immunity by activating NF-kappaB. Journal of Ethnopharmacology, 103, 217-222.
KUZNETSOV, O. I., MIL'KOVA, E. V., SOSNINA, A. E. & SOTNIKOVA, N. I. 2005. Antimicrobial
action of Lentinus edodes juice on human microflora. Zhurnal Mikrobiologii, Epidemiologii, I
Immunobiologii, 80-82.
KWEON, M.-H., KWON, S.-T., KWON, S.-H., MA, M.-S. & PARK, Y. I. 2002. Lowering effects in
plasma cholesterol and body weight by mycelial extracts of two mushrooms: Agaricus
blazai and Lentinus edodes. Korean Journal of Microbiology and Biotechnology, 30, 402409.
KWON, A. H., QIU, Z., HASHIMOTO, M., YAMAMOTO, K. & KIMURA, T. 2009. Effects of
medicinal mushroom (Sparassis crispa) on wound healing in streptozotocin-induced
diabetic rats. American Journal of Surgery, 197, 503-509.
LACHTER, J., YAMPOLSKY, Y., GAFNI-SCHIEBER, R. & WASSER, S. P. 2012. Yellow brain
culinary-medicinal mushroom, Tremella mesenterica Ritz.:Fr. (higher Basidiomycetes), is
subjectively but not objectively effective for eradication of Helicobacter pylori: a prospective
controlled trial. International Journal of Medicinal Mushrooms, 14, 55-63.
LAI, L. K., ABIDIN, N. Z., ABDULLAH, N. & SABARATNAM, V. 2010. Anti-Human Papillomavirus
(HPV) 16 E6 Activity of Ling Zhi or Reishi Medicinal Mushroom, Ganoderma lucidum (W.
Curt.: Fr.) P. Karst. (Aphyllophoromycetideae) Extracts. International Journal of Medicinal
Mushrooms, 12, 279-286.
LAKSHMI, B., SHEENA, N. & JANARDHANAN, K. K. 2009. Prevention of mammary
adenocarcinoma and skin tumour by Ganoderma lucidum, a medicinal mushroom
occurring in South India. Current Science, 97, 1658-1664.
LAM, S. K. & NG, T. B. 2001. Hypsin, a novel thermostable ribosome-inactivating protein with
antifungal and antiproliferative activities from fruiting bodies of the edible mushroom
Hypsizigus marmoreus. Biochemical and Biophysical Research Communications, 285,
1071-1075.
LAU, C. B. S., HO, C. Y., KIM, C. F., LEUNG, K. N., FUNG, K. P., TSE, T. F., CHAN, H. H. L. &
CHOW, M. S. S. 2004. Cytotoxic activities of Coriolus Versicolor (Yunzhi) extract on
human leukemia and lymphoma cells by induction of apoptosis. Life Sciences, 75, 797808.
LAVI, I., FRIESEM, D., GERESH, S., HADAR, Y. & SCHWARTZ, B. 2006. An aqueous
polysaccharide extract from the edible mushroom Pleurotus ostreatus induces antiproliferative and pro-apoptotic effects on HT-29 colon cancer cells. Cancer Letters, 244,
61-70.
LAVI, I., LEVINSON, D., PERI, I., NIMRI, L., HADAR, Y. & SCHWARTZ, B. 2010. Orally
administered glucans from the edible mushroom Pleurotus pulmonarius reduce acute
inflammation in dextran sulfate sodium-induced experimental colitis. British Journal of
Nutrition, 103, 393-402.
325
LAVI, I., NIMRI, L., LEVINSON, D., PERI, I., HADAR, Y. & SCHWARTZ, B. 2011. Glucans from the
edible mushroom Pleurotus pulmonarius inhibit colitis-associated colon carcinogenesis in
mice. J Gastroenterol.
LEE, B. R., KIM, S. Y., KIM, D. W., AN, J. J., SONG, H. Y., YOO, K. Y., KANG, T. C., WON, M. H.,
LEE, K. J., KIM, K. H., JOO, J. H., HAM, H. J., HUR, J. H., CHO, S. W., HAN, K. H., LEE,
K. S., PARK, J., CHOI, S. Y. & EUM, W. S. 2009a. Agrocybe chaxingu polysaccharide
prevent inflammation through the inhibition of COX-2 and NO production. BMB Rep, 42,
794-9.
LEE, C.-L., YANG, X. & WAN, J. M.-F. 2006. The culture duration affects the immunomodulatory
and anticancer effect of polysaccharopeptide derived from Coriolus versicolor. Enzyme and
Microbial Technology, 38, 14-21.
LEE, G., BYUN, H., YOON, K., LEE, J., CHOI, K. & JEUNG, E. 2009b. Dietary calcium and vitamin
D2 supplementation with enhanced Lentinula edodes improves osteoporosis-like
symptoms and induces duodenal and renal active calcium transport gene expression in
mice. European Journal of Nutrition, 48, 75-83.
LEE, I. P., KANG, B. H., ROH, J. K. & KIM, J. R. 2008. Lack of carcinogenicity of lyophilized
Agaricus blazei Murill in a F344 rat two year bioassay. Food and Chemical Toxicology, 46,
87-95.
LEE, J. & HONG, E. 2011. Agaricus blazei Murill enhances doxorubicin-induced apoptosis in
human hepatocellular carcinoma cells by NFkappaB-mediated increase of intracellular
doxorubicin accumulation. International Journal of Oncology, 38, 401-408.
LEE, J., OKA, K., WATANABE, O., HARA, H. & ISHIZUKA, S. 2011. Immunomodulatory effect of
mushrooms on cytotoxic activity and cytokine production of intestinal lamina propria
leukocytes does not necessarily depend on beta-glucan contents. Food Chemistry, 126,
1521-1526.
LEE, S. H., HWANG, H. S. & YUN, J. W. 2009c. Antitumor activity of water extract of a mushroom,
Inonotus obliquus, against HT-29 human colon cancer cells. Phytotherapy Research, 23,
1784-1789.
LEE, S. J., KIM, S. K., CHOI, W. S., KIM, W. J. & MOON, S. K. 2009d. Cordycepin causes
p21WAF1-mediated G2/M cell-cycle arrest by regulating c-Jun N-terminal kinase activation
in human bladder cancer cells. Archives of Biochemistry and Biophysics, 490, 103-109.
LEE, W. W., LEE, N., FUJII, H. & KANG, I. 2012. Active Hexose Correlated Compound promotes T
helper (Th) 17 and 1 cell responses via inducing IL-1beta production from monocytes in
humans. Cell Immunol, 275, 19-23.
LEI, H., MA, X. & WU, W. T. 2007. Anti-diabetic effect of an alpha-glucan from fruit body of Maitake
(Grifola Frondosa) on Kk-Ay mice. Journal of Pharmacy and Pharmacology, 59, 575-582.
LEVY, A. M., KITA, H., PHILLIPS, S. F., SCHKADE, P. A., DYER, P. D., GLEICH, G. J. &
DUBRAVEC, V. A. 1998. Eosinophilia and gastrointestinal symptoms after ingestion of
shiitake mushrooms. Journal of Allergy and Clinical Immunology, 101, 613-620.
LI, H., ZHANG, M. & MA, G. 2010a. Hypolipidemic effect of the polysaccharide from Pholiota
nameko. Nutrition, 26, 556-62.
LI, Y., ZHANG, G., NG, T. & WANG, H. 2010b. A novel lectin with antiproliferative and HIV-1
reverse transcriptase inhibitory activities from dried fruiting bodies of the monkey head
mushroom Hericium erinaceum. Journal of Biomedicine & Biotechnology, 2010, Article ID
716515.
326
LIANG, C., LI, H., ZHOU, H., ZHANG, S., LIU, Z., ZHOU, Q. & SUN, F. 2012. Recombinant Lz-8
from Ganoderma lucidum induces endoplasmic reticulum stress-mediated autophagic cell
death in SGC-7901 human gastric cancer cells. Oncol Rep, 27, 1079-89.
LIEN, H. M., LIN, H. W., WANG, Y. J., CHEN, L. C., YANG, D. Y., LAI, Y. Y. & HO, Y. S. 2009.
Inhibition of Anchorage-Independent Proliferation and G0/G1 Cell-Cycle Regulation in
Human Colorectal Carcinoma Cells by 4,7-Dimethoxy-5-methyl-l,3-benzodioxole Isolated
from the Fruiting Body of Antrodia camphorate. Evid Based Complement Alternat Med.
LIMA, C., CORDOVA, C. O. D., NOBREGA, O. D., FUNGHETTO, S. S. & KARNIKOWSKI, M. G.
D. 2011. Does the Agaricus blazei Murill mushroom have properties that affect the immune
system? An integrative review. Journal of Medicinal Food, 14, 2-8.
LIMA, C. U., SOUZA, V. C., MORITA, M. C., CHIARELLO, M. D. & DE OLIVEIRA KARNIKOWSKI,
M. G. 2012. Agaricus blazei Murrill and inflammatory mediators in elderly women: A
randomized clinical trial. Scandinavian Journal of Immunology, 75, 336-341.
LIN, C., SHEU, G., LIN, Y., YEH, C., HUANG, Y., LAI, Y., CHANG, J. & KO, J. 2010a. A new
immunomodulatory protein from Ganoderma microsporum inhibits epidermal growth factor
mediated migration and invasion in A549 lung cancer cells. Process Biochemistry, 45,
1537-1542.
LIN, H., CHEUNG, S. W., NESIN, M., CASSILETH, B. R. & CUNNINGHAM-RUNDLES, S. 2007.
Enhancement of umbilical cord blood cell hematopoiesis by maitake beta-glucan is
mediated by granulocyte colony-stimulating factor production. Clinical and Vaccine
Immunology, 14, 21-27.
LIN, H., DE STANCHINA, E., ZHOU, X. K., HONG, F., SEIDMAN, A., FORNIER, M., XIAO, W. L.,
KENNELLY, E. J., WESA, K., CASSILETH, B. R. & CUNNINGHAM-RUNDLES, S. 2010b.
Maitake beta-glucan promotes recovery of leukocytes and myeloid cell function in
peripheral blood from paclitaxel hematotoxicity. Cancer Immunology Immunotherapy, 59,
885-897.
LIN, H., DE STANCHINA, E., ZHOU, X. K., SHE, Y., HOANG, D., CHEUNG, S. W., CASSILETH,
B. & CUNNINGHAM-RUNDLES, S. 2009a. Maitake beta-glucan enhances umbilical cord
blood stem cell transplantation in the NOD/SCID mouse. Exp Biol Med (Maywood), 234,
342-53.
LIN, S.-B., LI, C.-H., LEE, S.-S. & KAN, L.-S. 2003. Triterpene-enriched extracts from Ganoderma
lucidum inhibit growth of hepatoma cells via suppressing protein kinase C, activating
mitogen-activated protein kinases and G2-phase cell cycle arrest. Life Sciences, 72, 23812390.
LIN, Y.-L., LEE, S.-S., HOU, S.-M. & CHIANG, B.-L. 2006. Polysaccharide purified from
Ganoderma lucidum induces gene expression changes in human dendritic cells and
promotes T helper 1 immune response in BALB/c mice. Molecular Pharmacology, 70, 637644.
LIN, Y. L., LIANG, Y. C., TSENG, Y. S., HUANG, H. Y., CHOU, S. Y., HSEU, R. S., HUANG, C. T.
& CHIANG, B. L. 2009b. An immunomodulatory protein, Ling Zhi-8, induced activation and
maturation of human monocyte-derived dendritic cells by the NF-kappaB and MAPK
pathways. Journal of Leukocyte Biology, 86, 877-889.
LIU, J., NING, A., CAO, J. & HUANG, M. 2009. Preliminary study on the anti-tumor effect of protein
extracts of Lentinus edodes C91-3 fermentation broth in mice with cervical cancer U14.
Zhongguo Weishengtaxixue Zazhi / Chinese Journal of Microecology, 21, 622-623.
LIU, J. K., HU, L., DONG, Z. J. & HU, Q. 2004a. DPPH radical scavenging activity of ten natural pterphenyl derivatives obtained from three edible mushrooms indigenous to China.
Chemistry and Biodiversity, 1, 601-605.
327
LIU, J. K., HU, L., DONG, Z. J. & HU, Q. 2004b. DPPH radical scavenging activity of ten natural pterphenyl derivatives obtained from three edible mushrooms indigenous to China. Chem
Biodivers, 1, 601-605.
LO, H. C., HSU, T. H. & CHEN, C. Y. 2008. Submerged culture mycelium and broth of Grifola
Frondosa improve glycemic responses in diabetic rats. American Journal of Chinese
Medicine, 36, 265-285.
LO, H. C. & WASSER, S. P. 2011. Medicinal mushrooms for glycemic control in diabetes mellitus:
History, current status, future perspectives, and unsolved problems (Review). International
LO, K. M. & CHEUNG, P. C. K. 2005. Antioxidant activity of extracts from the fruiting bodies of
Agrocybe Aegerita Var. Alba. Food Chemistry, 89, 533-539.
LOUIE, B., RAJAMAHANTY, S., WON, J., CHOUDHURY, M. & KONNO, S. 2010. Synergistic
potentiation of interferon activity with maitake mushroom D-fraction on bladder cancer
cells. BJU International, 105, 1011-1015.
LU, H., YANG, Y., GAD, E., INATSUKA, C., WENNER, C. A., DISIS, M. L. & STANDISH, L. J.
2011a. TLR2 agonist PSK activates human NK cells and enhances the antitumor effect of
HER2-targeted monoclonal antibody therapy. Clinical Cancer Research, 17, 6742-6753.
LU, H., YANG, Y., GAD, E., WENNER, C. A., CHANG, A., LARSON, E. R., DANG, Y., MARTZEN,
M., STANDISH, L. J. & DISIS, M. L. 2011b. Polysaccharide krestin is a novel TLR2 agonist
that mediates inhibition of tumor growth via stimulation of CD8 T cells and NK cells. Clinical
Cancer Research, 17, 67-76.
LU, H., YANG, Y., GAD, E., WENNER, C. A., CHANG, A., LARSON, E. R., DANG, Y., MARTZEN,
M., STANDISH, L. J. & DISIS, M. L. 2011c. Polysaccharide krestin is a novel TLR2 agonist
that mediates inhibition of tumor growth via stimulation of CD8 T cells and NK cells. Clinical
Cancer Res, 17, 67-76.
LU, Q. Y., SARTIPPOUR, M. R., BROOKS, M. N., ZHANG, Q., HARDY, M., GO, V. L., LI, F. P. &
HEBER, D. 2004. Ganoderma lucidum spore extract inhibits endothelial and breast cancer
cells in vitro. Oncology Reports, 12, 659-662.
LU, T. L., HUANG, G. J., LU, T. J., WU, J. B., WU, C. H., YANG, T. C., IIZUKA, A. & CHEN, Y. F.
2009. Hispolon from Phellinus linteus has antiproliferative effects via MDM2-recruited
ERK1/2 activity in breast and bladder cancer cells. Food and Chemical Toxicology, 47,
2013-2021.
LUK, S. U., LEE, T. K., LIU, J., LEE, D. T., CHIU, Y. T., MA, S., NG, I. O., WONG, Y. C., CHAN, F.
L. & LING, M. T. 2011. Chemopreventive effect of PSP through targeting of prostate
cancer stem cell-like population. PLoS ONE, 6, e19804.
LV, H., KONG, Y., YAO, Q., ZHANG, B., LENG, F. W., BIAN, H. J., BALZARINI, J., VAN DAMME,
E. & BAO, J. K. 2009. Nebrodeolysin, a novel hemolytic protein from mushroom Pleurotus
nebrodensis with apoptosis-inducing and anti-HIV-1 effects. Phytomedicine, 16, 198-205.
MAHMOOD, A., SUZITA, N., VIKINESWARY, S., NOORLIDAH, A., WONG, K. & HAPIPAH
MOHD, A. 2008. Effect of culinary-medicinal lion's mane mushroom, Hericium erinaceus
(Bull.: Fr.) Pers. (Aphyllophoromycetideae), on ethanol-induced gastric ulcers in rats.
MALLAVADHANI, U. V., SUDHAKAR, A. V. S., SATYANARAYANA, K. V. S., MAHAPATRA, A., LI,
W. & VANBREEMEN, R. B. 2006. Chemical and analytical screening of some edible
mushrooms. Food Chemistry, 95, 58-64.
328
MANESS, L., SNEED, N., HARDY, B., YU, J., AHMEDNA, M. & GOKTEPE, I. 2011. Antiproliferative effect of Pleurotus tuberregium against colon and cervical cancer cells. Journal
of Medicinal Plants Research, 5, 6650-6655.
MARTIN, K. R. 2010a. The bioactive agent ergothioneine, a key component of dietary mushrooms,
inhibits monocyte binding to endothelial cells characteristic of early cardiovascular disease.
Journal of Medicinal Food, 13, 1340-1346.
MARTIN, K. R. 2010b. Both common and specialty mushrooms inhibit adhesion molecule
expression and in vitro binding of monocytes to human aortic endothelial cells in a proinflammatory environment. Nutrition Journal, 9, (16 July 2010).
MARTIN, K. R. & BROPHY, S. K. 2010. Commonly consumed and specialty dietary mushrooms
reduce cellular proliferation in MCF-7 human breast cancer cells. Experimental Biology and
Medicine, 235, 1306-1314.
MARTINEZ-MONTEMAYOR, M. M., ACEVEDO, R. R., OTERO-FRANQUI, E., CUBANO, L. A. &
DHARMAWARDHANE, S. F. 2011. Ganoderma lucidum (Reishi) inhibits cancer cell
growth and expression of key molecules in inflammatory breast cancer. Nutrition and
Cancer, 63, 1085-1094.
MARTINS, P. R., GAMEIRO, M. C., CASTOLDI, L., ROMAGNOLI, G. G., LOPEZ, F. C., PINTO, A.
V., LOYOLA, W. & KANENO, R. 2008. Polysaccharide-rich fraction of Agaricus Brasiliensis
enhances the Candidacidal activity of murine marophages. Memorias Do Instituto Oswaldo
Cruz, 103, 244-250.
MARUYAMA, H. & IKEKAWA, T. 2007. Immunomodulation and antitumor activity of a mushroom
product, proflamin, isolated from Flammulina velutipes (W. Curt.: Fr.) Singer
(Agaricomycetideae). International Journal of Medicinal Mushrooms, 9, 109-122.
MASUDA, Y., ITO, K., KONISHI, M. & NANBA, H. 2010. A polysaccharide extracted from Grifola
frondosa enhances the anti-tumor activity of bone marrow-derived dendritic cell-based
immunotherapy against murine colon cancer. Cancer Immunology Immunotherapy, 59,
1531-1541.
MASUDA, Y., MATSUMOTO, A., TOIDA, T., OIKAWA, T., ITO, K. & NANBA, H. 2009.
Characterization and antitumor effect of a novel polysaccharide from Grifola frondosa.
MASUDA, Y., TOGO, T., MIZUNO, S., KONISHI, M. & NANBA, H. 2011. Soluble beta-glucan from
Grifola frondosa induces proliferation and Dectin-1/Syk signaling in resident macrophages
via the GM-CSF autocrine pathway. J Leukoc Biol.
MATHEW, J., SUDHEESH, N. P., RONY, K. A., SMINA, T. P. & JANARDHANAN, K. K. 2008.
Antioxidant and antitumor activities of cultured mycelium of culinary-medicinal paddy straw
mushroom Volvariella Volvacea (Bull.:Fr.) Singer (Agaricomycetideae). International
MATSUDA, H., AKAKI, J., NAKAMURA, S., OKAZAKI, Y., KOJIMA, H., TAMESADA, M. &
YOSHIKAWA, M. 2009. Apoptosis-inducing effects of sterols from the dried powder of
cultured mycelium of Cordyceps sinensis. Chem Pharm Bull (Tokyo), 57, 411-4.
MATSUMOTO, K., ITO, M., YAGYU, S., OGINO, H. & HIRONO, I. 1991. Carcinogenicity
examination of Agaricus bisporus, edible mushroom, in rats. Cancer Letters, 58, 87-90.
MATSUZAWA, T. 2006. Studies on antioxidant effects of culinary-medicinal bunashimeji
mushroom Hypsizygus marmoreus (Peck) Bigel. (Agaricomycetideae). International
329
MATTILA, P., KONKO, K., EUROLA, M., PIHLAVA, J. M., ASTOLA, J., VAHTERISTO, L.,
HIETANIEMI, V., KUMPULAINEN, J., VALTONEN, M. & PIIRONEN, V. 2001. Contents of
vitamins, mineral elements, and some phenolic compounds in cultivated mushrooms.
MCCORMACK, E., SKAVLAND, J., MUJIC, M., BRUSERUD & GJERTSEN, B. T. 2010. Lentinan:
hematopoietic, immunological, and efficacy studies in a syngeneic model of acute myeloid
leukemia. Nutrition and Cancer, 62, 574-583.
MEERA, C. R., SMINA, T. P., BALAN, N., MATHEW, J. & JANARDHANAN, K. K. 2009.
Antiarthritic activity of a polysaccharide-protein complex isolated from Phellinus rimosus
(Berk.) Pilat (Aphyllophoromycetideae) in Freund's complete adjuvant-induced arthritic rats.
MIYAMOTO, I., LIU, J., SHIMIZU, K., SATO, M., KUKITA, A., KUKITA, T. & KONDO, R. 2009.
Regulation of osteoclastogenesis by ganoderic acid DM isolated from Ganoderma lucidum.
European Journal of Pharmacology, 602, 1-7.
MIYAZAKI, H., GEMMA, H., KOSHIMIZU, N., SATO, M., ITO, I., SUDA, T., CHIDA, K. &
NAKAMURA, H. 2003. Hypersensitivity pneumonitis induced by Pleurotus eryngii spores a case report. Nihon Kokyuki Gakkai Zasshi - Journal of the Japanese Respiratory Society,
41, 827-833.
MIZUMOTO, H., OHNOGI, H., MIZUTANI, S., ENOKI, T., ASADA, K., SUGIMOTO, Y. & KATO, I.
2008. Mechanism of apoptosis induced by polyterpene from Buna-shimeji (Hypsizigus
marmoreus) in HL-60 cells. Nippon Shokuhin Kagaku Kogaku Kaishi = Journal of the
Japanese Society for Food Science and Technology, 55, 612-618.
MIZUNO, M. 2000. Anti-tumor polysaccharides from mushrooms during storage. Biofactors, 12,
275-281.
MIZUTANI, T., INATOMI, S., INAZU, A. & KAWAHARA, E. 2010. Hypolipidemic effect of Pleurotus
eryngii extract in fat-loaded mice. Journal of Nutritional Science and Vitaminology, 56, 4853.
MOHAMMED, A., ADELAIYE, A. B., ABUBAKAR, M. S. & ABDURAHMAN, E. M. 2007. Effects of
aqueous extract of Ganorderma Lucidum on blood glucose levels in normoglycemic and
alloxan-induced diabetic Wistar rats. Journal of Medicinal Plants Research, 1, 34-37.
MOJADADI, S., EBTEKAR, M. & HASSAN, Z. M. 2006. Immunomodulatory effects of Ganoderma
lucidum (W. Curt.:Fr.) P. Karst. (Aphyllophoromycetideae) on CD4+/CD8+ tumor infiltrating
lymphocytes in breast-cancer-bearing mice. International Journal of Medicinal Mushrooms,
8, 315-320.
MORI, K., INATOMI, S., OUCHI, K., AZUMI, Y. & TUCHIDA, T. 2009. Improving effects of the
mushroom Yamabushitake (Hericium erinaceus) on mild cognitive impairment: a doubleblind placebo-controlled clinical trial. Phytotherapy Research, 23, 367-372.
MORI, K., KOBAYASHI, C., TOMITA, T., INATOMI, S. & IKEDA, M. 2008. Antiatherosclerotic effect
of the edible mushrooms Pleurotus eryngii (Eringi), Grifola frondosa (Maitake), and
Hypsizygus marmoreus (Bunashimeji) in apolipoprotein E-deficient mice. Nutrition
Research, 28, 335-342.
MORI, K., OBARA, Y., MORIYA, T., INATOMI, S. & NAKAHATA, N. 2011. Effects of Hericium
erinaceus on amyloid beta(25-35) peptide-induced learning and memory deficits in mice.
Biomedical Research, 32, 67-72.
MORO, C., PALACIOS, I., LOZANO, M., D'ARRIGO, M., GUILLAMON, E., VILLARES, A.,
MARTINEZ, J. A. & GARCIA-LAFUENTE, A. 2012. Anti-inflammatory activity of methanolic
330
extracts from edible mushrooms in LPS activated RAW 264.7 macrophages. Food
Chemistry, 130, 350-355.
NAGANO, M., SHIMIZU, K., KONDO, R., HAYASHI, C., SATO, D., KITAGAWA, K. & OHNUKI, K.
2010. Reduction of depression and anxiety by 4 weeks Hericium erinaceus intake.
Biomedical Research-Tokyo, 31, 231-237.
NAJAFZADEH, M., REYNOLDS, P. D., BAUMGARTNER, A., JERWOOD, D. & ANDERSON, D.
2007. Chaga mushroom extract inhibits oxidative DNA damage in lymphocytes of patients
with inflammatory bowel disease. Biofactors, 31, 191-200.
NAKAZAWA, T. & TOCHIGI, T. 1989. Hypersensitivity pneumonitis due to mushroom (Pholiota
nameko) spores. Chest, 95, 1149-1151.
NG, M. L. & YAP, A. T. 2002. Inhibition of human colon carcinoma development by lentinan from
shiitake mushrooms (Lentinus edodes). J of Alternative and Complementary Medicine, 8,
581-589.
NOGUCHI, M., KAKUMA, T., TOMIYASU, K., KURITA, Y., KUKIHARA, H., KONISHI, F.,
KUMAMOTO, S., SHIMIZU, K., KONDO, R. & MATSUOKA, K. 2008a. Effect of an extract
of Ganoderma lucidum in men with lower urinary tract symptoms: a double-blind, placebocontrolled randomized and dose-ranging study. Asian Journal of Andrology, 10, 651-658.
NOGUCHI, M., KAKUMA, T., TOMIYASU, K., YAMADA, A., ITOH, K., KONISHI, F., KUMAMOTO,
S., SHIMIZU, K., KONDO, R. & MATSUOKA, K. 2008b. Randomized clinical trial of an
ethanol extract of Ganoderma lucidum in men with lower urinary tract symptoms. Asian
Journal of Andrology, 10, 777-785.
NOGUSA, S., GERBINO, J. & RITZ, B. W. 2009. Low-dose supplementation with active hexose
correlated compound improves the immune response to acute influenza infection in
C57BL/6 mice. Nutrition Research, 29, 139-143.
NOVAES, M. R., VALADARES, F., REIS, M. C., GONCALVES, D. R. & MENEZES MDA, C. 2011.
The effects of dietary supplementation with Agaricales mushrooms and other medicinal
fungi on breast cancer: evidence-based medicine. Clinics (Sao Paulo), 66, 2133-9.
NURK, E., REFSUM, H., DREVON, C. A., TELL, G. S., NYGAARD, H. A., ENGEDAL, K. & SMITH,
A. D. 2010. Cognitive performance among the elderly in relation to the intake of plant
foods. The Hordaland Health Study. British Journal of Nutrition, 104, 1190-1201.
OBA, K., KOBAYASHI, M., MATSUI, T., KODERA, Y. & SAKAMOTO, J. 2009. Individual patient
based meta-analysis of lentinan for unresectable/recurrent gastric cancer. Anticancer
Research, 29, 2739-2745.
OBA, K., TERAMUKAI, S., KOBAYASHI, M., MATSUI, T., KODERA, Y. & SAKAMOTO, J. 2007.
Efficacy of adjuvant immunochemotherapy with polysaccharide K for patients with curative
resections of gastric cancer. Cancer Immunology Immunotherapy, 56, 905-911.
OBI, N., HAYASHI, K., MIYAHARA, T., SHIMADA, Y., TERASAWA, K., WATANABE, M.,
TAKEYAMA, M., OBI, R. & OCHIAI, H. 2008. Inhibitory effect of TNF-alpha produced by
macrophages stimulated with Grifola Frondosa extract (ME) on the growth of influenza
a/Aichi/2/68 virus in MDCK cells. American Journal of Chinese Medicine, 36, 1171-1183.
OFODILE, L. N., OGBE, A. O. & OLADIPUPO, O. 2011. Effect of the mycelial culture of
Ganoderma lucidum on human pathogenic bacteria. International Journal of Biology, 3,
111-114.
OH, T. W., KIM, Y. A., JANG, W. J., BYEON, J. I., RYU, C. H., KIM, J. O. & HA, Y. L. 2010.
Semipurified fractions from the submerged-culture broth of Agaricus blazei Murill reduce
331
blood glucose levels in streptozotocin-induced diabetic rats. Journal of Agricultural and

OHNO, N., FURUKAWA, M., MIURA, N. N., ADACHI, Y., MOTOI, M. & YADOMAE, T. 2001.
Antitumor beta glucan from the cultured fruit body of Agaricus blazei. Biological and
Pharmaceutical Bulletin, 24, 820-828.
OHNO, S., SUMIYOSHI, Y., HASHINE, K., SHIRATO, A., KYO, S. & INOUE, M. 2011. Phase I
clinical study of the dietary supplement, Agaricus blazei Murill, in cancer patients in
remission. Evidence-Based Complementary and Alternative Medicine, 1-9.
OHTSUKI, M., UMESHITA, K., KOKEAN, Y., NISHII, T., SAKAKURA, H., YANAGITA, T. &
FURUICHI, Y. 2006. The hypolipidemic effects of some edible mushrooms on growing rats.
Journal of the Japanese Society for Food Science and Technology-Nippon Shokuhin
Kagaku Kogaku Kaishi, 53, 612-618.
OHTSUKI, M., UMESHITA, K., KOKEAN, Y., NISHII, T., SAKAKURA, H., YANAGITA, T.,
HISAMATSU, M. & FURUICHI, Y. 2007. Suppressive effects of Bunashimeji (Hypsizigus
Marmoreus) on triacylglycerol accumulation in C57bl/6j mice. Journal of the Japanese
Society for Food Science and Technology-Nippon Shokuhin Kagaku Kogaku Kaishi, 54,
167-172.
OKE, F. & ASLIM, B. 2011. Protective effect of two edible mushrooms against oxidative cell
damage and their phenolic composition. Food Chemistry, 128, 613-619.
OKUBO, H., MIYAKE, Y., SASAKI, S., MURAKAMI, K., TANAKA, K., FUKUSHIMA, W.,
KIYOHARA, C., TSUBOI, Y., YAMADA, T., OEDA, T., SHIMADA, H., KAWAMURA, N.,
SAKAE, N., FUKUYAMA, H., HIROTA, Y. & NAGAI, M. 2011. Dietary patterns and risk of
Parkinson's disease: a case-control study in Japan. European Journal of Neurology.
OMAR, N. A. M., ABDULLAH, N., KUPPUSAMY, U. R., ABDULLA, M. A. & SABARATNAM, V.
2011. Nutritional composition, antioxidant activities, and antiulcer potential of Lentinus
squarrosulus (Mont.) mycelia extract. Evidence-Based Complementary and Alternative
Medicine, 1-8.
OU, H. T., SHIEH, C. J., CHEN, J. Y. & CHANG, H. M. 2005. The antiproliferative and
differentiating effects of human leukemic U937 cells are mediated by cytokines from
activated mononuclear cells by dietary mushrooms. Journal of Agricultural and Food
Chemistry, 53, 300-305.
OUZOUNI, P. K., VELTSISTAS, P. G., PALEOLOGOS, E. K. & RIGANAKOS, K. A. 2007.
Determination of metal content in wild edible mushroom species from regions of Greece.
Journal of Food Composition and Analysis, 20, 480-486.
PALOMARES, M. R., RODRIGUEZ, J., PHUNG, S., STANCZYK, F. Z., LACEY, S. F., SYNOLD, T.
W., DENISON, S., FRANKEL, P. H. & CHEN, S. 2011. A dose-finding clinical trial of
mushroom powder in postmenopausal breast cancer survivors for secondary breast cancer
prevention. Journal of Clinical Oncology, 29, Abstract 1582.
PARAMESWARI, V. & CHINNASWAMY, P. 2011. An in vitro study of the inhibitory effect of
Pleurotus florida a higher fungi on human pathogens. Journal of Pharmacy Research, 4,
1948-1949.
PARK, J., OH, W., KWAK, D., KIM, M., SEO, G., HONG, S. & RHEE, M. 2011. The anti-platelet
activity of Hypsizygus marmoreus extract is involved in the suppression of intracellular
calcium mobilization and integrin α IIbβ 3 activation. Journal of Medicinal Plants
Research, 5, 2369-2377.
332
PARK, Y. K., LEE, H. B., JEON, E. J., JUNG, H. S. & KANG, M. H. 2004. Chaga mushroom extract
inhibits oxidative DNA damage in human lymphocytes as assessed by Comet assay.
Biofactors, 21, 109-112.
PATEL, S. & GOYAL, A. 2012. Recent developments in mushrooms as anti-cancer therapeutics: a
review. 3 Biotech, 2, 1-15.
PELLEY, R. P. & STRICKLAND, F. M. 2000. Plants, polysaccharides, and the treatment and
prevention of neoplasia. Critical Reviews in Oncology, 11, 189-225.
PERCARIO, S., ODORIZZI, V. F., SOUZA, D. R., PINHEL, M. A., GENNARI, J. L., GENNARI, M.
S. & GODOY, M. F. 2008. Edible mushroom Agaricus sylvaticus can prevent the onset of
atheroma plaques in hypercholesterolemic rabbits. Cellular and Molecular Biology, 54
Suppl, OL1055-1061.
PETERMANN, I., TRIGGS, C. M., HUEBNER, C., HAN, D., GEARRY, R. B., BARCLAY, M. L.,
DEMMERS, P. S., MCCULLOCH, A. & FERGUSON, L. R. 2009. Mushroom intolerance: a
novel diet-gene interaction in Crohn's disease. British Journal of Nutrition, 102, 506-508.
PETROVA, R. D. 2012. New scientific approaches to cancer treatment: can medicinal mushrooms
defeat the curse of the century? International Journal of Medicinal Mushrooms, 14, 1-20.
PETROVA, R. D., WASSER, S. P., MAHAJNA, J. A., DENCHEV, C. M. & NEVO, E. 2005.
Potential role of medicinal mushrooms in breast cancer treatment: Current knowledge and
future perspectives. International Journal of Medicinal Mushrooms, 7, 141-155.
PILLAI, T. G., NAIR, C. K. K. & JANARDHANAN, K. K. 2010. Enhancement of repair of radiation
induced DNA strand breaks in human cells by Ganoderma mushroom polysaccharides.
PILLAI, T. G., SALVI, V. P., MAURYA, D. K., NAIR, C. K. K. & JANARDHANAN, K. K. 2006.
Prevention of radiation-induced damages by aqueous extract of Ganoderma lucidum
occurring in southern parts of India. Current Science, 91, 341-344.
PINHEIRO, F., FARIA, R. R., DE CAMARGO, J. L., SPINARDI-BARBISAN, A. L., DA EIRA, A. F. &
BARBISAN, L. F. 2003. Chemoprevention of preneoplastic liver foci development by
dietary mushroom Agaricus blazei Murrill in the rat. Food and Chemical Toxicology, 41,
1543-1550.
PREUSS, H. G., ECHARD, B., BAGCHI, D. & PERRICONE, N. V. 2010. Maitake mushroom
extracts ameliorate progressive hypertension and other chronic metabolic perturbations in
aging female rats. International Journal of Medical Sciences, 7, 169-180.
PREUSS, H. G., ECHARD, B., BAGCHI, D., PERRICONE, N. V. & ZHUANG, C. 2007. Enhanced
insulin-hypoglycemic activity in rats consuming a specific glycoprotein extracted from
maitake mushroom. Molecular and Cellular Biochemistry, 306, 105-113.
PRICE, L. A., WENNER, C. A., SLOPER, D. T., SLATON, J. W. & NOVACK, J. P. 2010. Role for
toll-like receptor 4 in TNF-alpha secretion by murine macrophages in response to
polysaccharide Krestin, a Trametes versicolor mushroom extract. Fitoterapia, 81, 914-919.
PYO, P., LOUIE, B., RAJAMAHANTY, S., CHOUDHURY, M. & KONNO, S. 2008. Possible
immunotherapeutic potentiation with D-Fraction in prostate cancer cells. Journal of
Hematology and Oncology, 1, 25.
QIAN, Z. M., XU, M. F. & TANG, P. L. 1997. Polysaccharide Peptide (PSP) Restores
Immunosuppression Induced by Cyclophosphamide in Rats. American Journal of Chinese
Medicine, 25, 27-35.
333
RABINOVICH, M., FIGLAS, D., DELMASTRO, S. & CURVETTO, N. 2007. Copper- and zincenriched mycelium of Agaricus blazei Murrill: Bioaccumulation and bioavailability. Journal
of Medicinal Food, 10, 175-183.
RAMBERG, J. E., NELSON, E. D. & SINNOTT, R. A. 2010. Immunomodulatory dietary
polysaccharides: a systematic review of the literature. Nutrition Journal, 9, Issue 54 (on-line
journal).
RAO KOYYALAMUDI, S., SANG-CHUL, J., PANG, G., TEAL, A. & BIGGS, T. 2011. Concentration
of vitamin D2 in white button mushrooms (Agaricus bisporus) exposed to pulsed UV light.
Journal of Food Composition and Analysis, 24, 976-979.
REIS, F. S., MARTINS, A., BARROS, L. & FERREIRA, I. C. 2012. Antioxidant properties and
phenolic profile of the most widely appreciated cultivated mushrooms: a comparative study
between in vivo and in vitro samples. Food Chem Toxicol, 50, 1201-7.
REN, G., ZHAO, Y.-P., YANG, L. & FU, C.-X. 2008a. Anti-proliferative effect of clitocine from the
mushroom Leucopaxillus giganteus on human cervical cancer HeLa cells by inducing
apoptosis. Cancer Letters, 262, 190-200.
REN, Z., GUO, Z., MEYDANI, S. N. & WU, D. 2008b. White button mushroom enhances
maturation of bone marrow-derived dendritic cells and their antigen presenting function in
mice. Journal of Nutrition, 138, 544-550.
RHEE, Y., JEONG, S., LEE, H., LEE, H., KOH, W., JUNG, J., KIM, S. & KIM, S. 2012. Inhibition of
STAT3 signaling and induction of SHP1 mediate antiangiogenic and antitumor activities of
ergosterol peroxide in U266 multiple myeloma cells. BMC Cancer, 12, 28
RIBEIRO-SANTOS, G., BARBISAN, L. F., LOPES, F. C., SPINARDI-BARBISAN, A. L., DA EIRA,
A. F. & KANENO, R. 2008. Lack of chemopreventive activity of Agaricus blazei mushroom
on the development of 1,2-dimethylhydrazine-induced colonic aberrant crypt foci in rats.
Nutrition and Cancer, 60, 768-775.
ROCHA, N. S., BARBISAN, L. F., DE OLIVEIRA, M. L. C. & DE CAMARGO, J. L. V. 2002.
Mushroom-derived preparations in the prevention of H2O2-induced oxidative damage to
cellular DNA. Teratogenesis Carcinogenesis and Mutagenesis, 22, 103-111.
RONDANELLI, M., OPIZZI, A. & MONTEFERRARIO, F. 2009. The biological activity of betaglucans. Minerva Medica, 100, 237-245.
RONY, K. A., MATHEW, J., NEENU, P. P. & JANARDHANAN, K. K. 2011. Ganoderma lucidum
(Fr.) P. Karst occurring in South India attenuates gastric ulceration in rats. Indian Journal of
Natural Products and Resources, 2, 19-27.
ROP, O., MLCEK, J. & JURIKOVA, T. 2009. Beta-glucans in higher fungi and their health effects.
Nutrition Reviews, 67, 624-631.
ROUPAS, P., KEOGH, J., NOAKES, M., MARGETTS, C. & TAYLOR, P. 2010a. Mushrooms and
agaritine: A mini-review. Journal of Functional Foods, 2, 91-98.
ROUPAS, P., KEOGH, J., NOAKES, M., MARGETTS, C. & TAYLOR, P. 2010b. Mushrooms and
agaritine: A mini-review. Journal of Functional Foods, 2, 91-98.
ROUPAS, P., KEOGH, J., NOAKES, M., MARGETTS, C. & TAYLOR, P. 2012. The role of edible
mushrooms in health: Evaluation of the evidence. Journal of Functional Foods, In Press,
http://dx.doi.org/10.1016/j.jff.2012.05.003.
ROVENSKY, J., STANCIKOVA, M., SVIK, K., BAUEROVA, K. & JURCOVICOVA, J. 2011. The
effects of beta-glucan isolated from Pleurotus ostreatus on methotrexate treatment in rats
with adjuvant arthritis. Rheumatology International, 31, 507-511.
334
RUBEL, R., DALLA SANTA, H. S., BONATTO, S. J., BELLO, S., FERNANDES, L. C., DI
BERNARDI, R., GERN, J., SANTOS, C. A. & SOCCOL, C. R. 2010. Medicinal mushroom
Ganoderma lucidum (Leyss: Fr) Karst. triggers immunomodulatory effects and reduces
nitric oxide synthesis in mice. J Med Food, 13, 142-8.
RUBEL, R., DALLA SANTA, H. S., FERNANDES, L. C., BONATTO, S. J. R., BELLO, S.,
FIGUEIREDO, B. C., LIMA, J. H. C., SANTOS, C. A. M. & SOCCOL, C. R. 2011.
Hypolipidemic and antioxidant properties of Ganoderma lucidum (Leyss:Fr) Karst used as
a dietary supplement. World Journal of Microbiology & Biotechnology, 27, 1083-1089.
RUBEL, R., SANTA, H. S. D., FERNANDES, L. C., FILHO, J. H. C. L., FIGUEIREDO, B. C., DI
BERNARDI, R., MORENO, A. N., LEIFA, F. & SOCCOL, C. R. 2008. High
immunomodulatory and preventive effects against sarcoma 180 in mice fed with Ling Zhi or
Reishi mushroom Ganoderma lucidum (W. Curt.: Fr.) P. Karst. (Aphyllophoromycetideae)
mycelium. International Journal of Medicinal Mushrooms, 10, 37-48.
RUSSO, A., CARDILE, V., PIOVANO, M., CAGGIA, S., ESPINOZA, C. L. & GARBARINO, J. A.
2010. Pro-apoptotic activity of ergosterol peroxide and (22E)-ergosta-7,22-dien-5 alphahydroxy-3,6-dione in human prostate cancer cells. Chemico-Biological Interactions, 184,
352-358.
RUSSO, A., PIOVANO, M., CLERICUZIO, M., LOMBARDO, L., TABASSO, S., CHAMY, M. C.,
VIDARI, G., CARDILE, V., VITA-FINZI, P. & GARBARINO, J. A. 2007. Putrescine-1,4dicinnamide from Pholiota spumosa (Basidiomycetes) inhibits cell growth of human
prostate cancer cells. Phytomedicine, 14, 185-191.
SAIF, A., LINDEQUIST, U. & WENDE, K. 2007. Stimulating effects of Grifola frondosa (Maitake) on
human osteoblastic cell cultures. Journal of Natural Medicines, 61, 231-238.
SAITOH, H., FENG, W., MATSUZAWA, T. & IKEKAWA, T. 1997. Antitumor activity of Hypsizigus
marmoreus. II. Preventive effect against lung metastasis of Lewis lung carcinoma.
Yakugaku Zasshi, 117, 1006-1010.
SAKAMOTO, J., MORITA, S., OBA, K., MATSUI, T., KOBAYASHI, M., NAKAZATO, H. & OHASHI,
Y. 2006. Efficacy of adjuvant immunochemotherapy with polysaccharide K for patients with
curatively resected colorectal cancer: a meta-analysis of centrally randomized controlled
clinical trials. Cancer Immunology Immunotherapy, 55, 404-411.
SANDEEP, R., GAURAV, S., NAVNEET, N., NAGPAL, M. A. & SINGH, G. S. 2011. Preparation,
characterization, and biological properties of beta-glucans. Journal of Advanced
Pharmaceutical Technology and Research, 2, 94-103.
SANG CHUL, J., RAO KOYYALAMUDI, S., YONG TAE, J., CHI HYUN, S. & PANG, G. 2012.
Macrophage immunomodulating and antitumor activities of polysaccharides isolated from
Agaricus bisporus white button mushrooms. Journal of Medicinal Food, 15, 58-65.
SANG CHUL, J., YONG TAE, J., BYUNG KEUN, Y., REZUANUL, I., SUNDAR RAO, K., PANG,
G., KAI YIP, C. & CHI HYUN, S. 2010. White button mushroom ( Agaricus bisporus) lowers
blood glucose and cholesterol levels in diabetic and hypercholesterolemic rats. Nutrition
Research, 30, 49-56.
SANODIYA, B. S., THAKUR, G. S., BAGHEL, R. K., PRASAD, G. B. & BISEN, P. S. 2009.
Ganoderma lucidum: a potent pharmacological macrofungus. Curr Pharm Biotechnol, 10,
717-42.
SANZEN, I., IMANISHI, N., TAKAMATSU, N., KONOSU, S., MANTANI, N., TERASAWA, K.,
TAZAWA, K., ODAIRA, Y., WATANABE, M., TAKEYAMA, M. & OCHIAI, H. 2001. Nitric
oxide-mediated antitumor activity induced by the extract from Grifola frondosa (Maitake
mushroom) in a macrophage cell line, RAW264.7. Journal of Experimental and Clinical
335
SARANGI, I., GHOSH, D., BHUTIA, S. K., MALLICK, S. K. & MAITI, T. K. 2006. Anti-tumor and
immunomodulating effects of Pleurotus ostreatus mycelia-derived proteoglycans.
International Immunopharmacology, 6, 1287-1297.
SATO, N., ZHANG, Q., MA, C. M. & HATTORI, M. 2009. Anti-human immunodeficiency virus-1
protease activity of new lanostane-type triterpenoids from Ganoderma sinense. Chemical
and Pharmaceitical Bulletin (Tokyo), 57, 1076-1080.
SAVOIE, J. M., MINVIELLE, N. & LARGETEAU, M. 2008. Radical-scavenging properties of
extracts from the white button mushroom, Agaricus Bisporus. Journal of the Science of
Food and Agriculture, 88, 970-975.
SCHNEIDER, I., KRESSEL, G., MEYER, A., KRINGS, U., BERGER, R. G. & HAHN, A. 2011. Lipid
lowering effects of oyster mushroom (Pleurotus ostreatus) in humans. Journal of
Functional Foods, 3, 17-24.
SELVI, S., UMADEVI, P., MURUGAN, S. A. & SENAPATHY, J. G. 2011. Anticancer potential
evoked by Pleurotus florida and Calocybe indica using T 24 urinary bladder cancer cell
line. African Journal of Biotechnology, 10, 7279-7285.
SETO, S. W., LAM, T. Y., TAM, H. L., AU, A. L., CHAN, S. W., WU, J. H., YU, P. H., LEUNG, G.
P., NGAI, S. M., YEUNG, J. H., LEUNG, P. S., LEE, S. M. & KWAN, Y. W. 2009. Novel
hypoglycemic effects of Ganoderma lucidum water-extract in obese/diabetic (+db/+db)
mice. Phytomedicine, 16, 426-36.
SHAH, S. K., WALKER, P. A., MOORE-OLUFEMI, S. D., SUNDARESAN, A., KULKARNI, A. D. &
ANDRASSY, R. J. 2011. An evidence-based review of a Lentinula edodes mushroom
extract as complementary therapy in the surgical oncology patient. Journal of Parenteral
and Enteral Nutrition, 35, 449-458.
SHEN, J., REN, H., TOMIYAMA-MIYAJI, C., SUGA, Y., SUGA, T., KUWANO, Y., IIAI, T.,
HATAKEYAMA, K. & ABO, T. 2007. Potentiation of intestinal immunity by micellary
mushroom extracts. Biomedical Research, 28, 71-77.
SHEN, J., TANIDA, M., FUJISAKI, Y., HORII, Y., HASHIMOTO, K. & NAGAI, K. 2009. Effect of the
culture extract of Lentinus edodes mycelia on splenic sympathetic activity and cancer cell
proliferation. Autonomic Neuroscience: Basic and Clinical, 145, 50-54.
SHEPHARD, S. E., GUNZ, D. & SCHLATTER, C. 1995. Genotoxicity of agaritine in the lacI
transgenic mouse mutation assay: evaluation of the health risk of mushroom consumption.
Food and Chemical Toxicology, 33, 257-264.
SHEU, F., CHIEN, P. J., CHIEN, A. L., CHEN, Y. F. & CHIN, K. L. 2004. Isolation and
Characterization of an Immunomodulatory Protein (App), From the Jew's Ear Mushroom
Auricularia Polytricha. Food Chemistry, 87, 593-600.
SHI, Y.-L., BENZIE, I. F. F. & BUSWELL, J. A. 2002. Role of tyrosinase in the genoprotective effect
of the edible mushroom, Agaricus bisporus. Life Sciences, 70, 1595-1608.
SHIBATA, M., SHIMURA, T., NISHINA, Y., GONDA, K., MATSUO, S., ABE, H., YAJIMA, Y.,
NAKAMURA, I., OHKI, S. & TAKENOSHITA, S. 2011. PSK decreased FOLFOX4-induced
peripheral neuropathy and bone marrow suppression in patients with metastatic colorectal
cancer. Gan To Kagaku Ryoho, 38, 797-801.
SHIBATA, Y., KASHIWAGI, B., ARAI, S., FUKABORI, Y. & SUZUKI, K. 2005. Administration of
extract of mushroom Phellinus linteus induces prostate enlargement with increase in
stromal component in experimentally developed rat model of benign prostatic hyperplasia.
Urology, 66, 455-460.
336
SHIMIZU, K., NAGANO, M., HAYASHI, C., OHNUKI, H., FURUTA, S., KONDO, R., SATO, D.,
KITAGAWA, K. & OHNUKI, K. 2010. Multifunctional biological activities of Hericium
erinaceum - the investigation of the clinical effects of the fruiting body of H. erinaceum on
menopause, depression, sleep quality and indefinite complaints: multifunctional biological
activities of natural products (3). Aroma Research, 11, 276-283.
SHIMIZU, K., YAMANAKA, M., GYOKUSEN, M., KANEKO, S., TSUTSUI, M., SATO, J., SATO, I.,
SATO, M. & KONDO, R. 2006. Estrogen-like activity and prevention effect of bone loss in
calcium deficient ovariectomized rats by the extract of Pleurotus eryngii. Phytotherapy
Research, 20, 659-664.
SHIMOKAWA, K., MASHIMA, I., ASAI, A., OHNO, T., YAMADA, K., KITA, M. & UEMURA, D.
2008. Biological activity, structural features, and synthetic studies of (-)-ternatin, a potent
fat-accumulation inhibitor of 3T3-L1 adipocytes. Chemistry, an Asian Journal, 3, 438-446.
SHIN, A., KIM, J., LIM, S. Y., KIM, G., SUNG, M. K., LEE, E. S. & RO, J. 2010. Dietary mushroom
intake and the risk of breast cancer based on hormone receptor status. Nutrition and
Cancer, 62, 476-483.
SHNYREVA, A. V., SONG, W. & VAN GRIENSVEN, L. 2010. Extracts of medicinal mushrooms
Agaricus bisporus and Phellinus linteus induce proapoptotic effects in the human leukemia
cell line K562. International Journal of Medicinal Mushrooms, 12, 167-175.
SHOMORI, K., YAMAMOTO, M., ARIFUKU, I., TERAMACHI, K. & ITO, H. 2009. Antitumor effects
of a water-soluble extract from Maitake (Grifola frondosa) on human gastric cancer cell
lines. Oncology Reports, 22, 615-620.
SIGNORETTO, C., BURLACCHINI, G., MARCHI, A., GRILLENZONI, M., CAVALLERI, G., CIRIC,
L., LINGSTROM, P., PEZZATI, E., DAGLIA, M., ZAURA, E., PRATTEN, J., SPRATT, D.
A., WILSON, M. & CANEPARI, P. 2011. Testing a low molecular mass fraction of a
mushroom (Lentinus edodes) extract formulated as an oral rinse in a cohort of volunteers.
Journal of Biomedicine and Biotechnology.
SIMON, R. R., PHILLIPS, K. M., HORST, R. L. & MUNRO, I. C. 2011. Vitamin D mushrooms:
comparison of the composition of button mushrooms (Agaricus bisporus) treated
postharvest with UVB light or sunlight. Journal of Agricultural and Food Chemistry, 59,
8724-8732.
SLIVA, D. 2010. Medicinal mushroom Phellinus linteus as an alternative cancer therapy (Review).
Experimental and Therapeutic Medicine, 1, 407-411.
SLIVA, D., JEDINAK, A., KAWASAKI, J., HARVEY, K. & SLIVOVA, V. 2008. Phellinus linteus
suppresses growth, angiogenesis and invasive behaviour of breast cancer cells through
the inhibition of AKT signalling. British Journal of Cancer, 98, 1348-1356.
SOARES, A. A., SOUZA, C. G. M., DANIEL, F. M., FERRARI, G. P., DA COSTA, S. M. G. &
PERALTA, R. M. 2009. Antioxidant activity and total phenolic content of Agaricus
Brasiliensis (Agaricus Blazei Murril) in two stages of maturity. Food Chemistry, 112, 775781.
SOARES, R., MEIRELES, M., ROCHA, A., PIRRACO, A., OBIOL, D., ALONSO, E., JOOS, G. &
BALOGH, G. 2011. Maitake (D fraction) mushroom extract induces apoptosis in breast
cancer cells by BAK-1 gene activation. Journal of Medicinal Food, 14, 563-572.
SOBOLEVA, A. I. U., KRASNOPOL'SKAIA, L. M., FEDOROVA, G. B. & KATRUKHA, G. S. 2006.
Antibiotic properties of the strains of the basidiomycete Lentinus edodes (Berk.) sing.
Antibiotiki Khimioterapiya, 51, 3-8.
337
SON, C. G., SHIN, J. W., CHO, J. H., CHO, C. K., YUN, C. H., CHUNG, W. & HAN, S. H. 2006.
Macrophage activation and nitric oxide production by water soluble components of
Hericium erinaceum. International Immunopharmacology, 6, 1363-1369.
SONG, K., LI, G., KIM, J., JING, K., KIM, T., KIM, J., SEO, S., YOO, J., PARK, H., HWANG, B.,
LIM, K. & YOON, W. 2011. Protein-bound polysaccharide from Phellinus linteus inhibits
tumor growth, invasion, and angiogenesis and alters Wnt/beta-catenin in SW480 human
colon cancer cells. BMC Cancer, 11, (22 July 2011).
SONG, Y. S., KIM, S. H., SA, J. H., JIN, C., LIM, C. J. & PARK, E. H. 2003. Anti-angiogenic,
antioxidant and xanthine oxidase inhibition activities of the mushroom Phellinus linteus.
Journal of Ethnopharmacology, 88, 113-116.
SONG, Z., JIA, L., XU, F., MENG, F., DENG, P., FAN, K. & LIU, X. 2009. Characteristics of Seenriched mycelia by Stropharia rugoso-annulata and its antioxidant activities in vivo. Biol
Trace Elem Res, 131, 81-9.
SORIMACHI, K., IKEHARA, Y., MAEZATO, G., OKUBO, A., YAMAZAKI, S., AKIMOTO, K. &
NIWA, A. 2001. Inhibition by Agaricus Blazei Murill fractions of cytopathic effect induced by
western equine encephalitis (WEE) virus on VERO cells in vitro. Bioscience Biotechnology
and Biochemistry, 65, 1645-1647.
SORIMACHI, K. & KOGE, T. 2008. Agaricus blazei water extracts as alternative medicines.
Current Pharmaceutical Analysis, 4, 39-43.
SOUMYA, C., GUNJAN, B., BASU, S. K. & KRISHNENDU, A. 2011. Antineoplastic effect of
mushrooms: a review. Australian Journal of Crop Science, 5, 904-911.
SOUZA-PACCOLA, E. A., BOMFETI, C. A., FA?VARO, L. C. L., FONSECA, I. C. B. & PACCOLAMEIRELLES, L. D. 2004. Antimutagenic action of Lentinula edodes and Agaricus blazei on
Aspergillus nidulans conidia. Brazilian Journal of Microbiology, 35, 311-315.
STAMETS, P. 2005. Notes on nutritional properties of culinary-medicinal mushrooms. International
STANDISH, L. J., WENNER, C. A., SWEET, E. S., BRIDGE, C., NELSON, A., MARTZEN, M.,
NOVACK, J. & TORKELSON, C. 2008. Trametes versicolor mushroom immune therapy in
breast cancer. Journal of the Society for Integrative Oncology, 6, 122-128.
STANLEY, G., HARVEY, K., SLIVOVA, V., JIANG, J. & SLIVA, D. 2005. Ganoderma lucidum
suppresses angiogenesis through the inhibition of secretion of VEGF and TGF-beta1 from
prostate cancer cells. Biochemical and Biophysical Research Communications, 330, 46-52.
STEPHENSEN, C. B., ZEROFSKY, M., BURNETT, D. J., LIN, Y. P., HAMMOCK, B. D., HALL, L.
M. & MCHUGH, T. 2012. Ergocalciferol from Mushrooms or Supplements Consumed with
a Standard Meal Increases 25-Hydroxyergocalciferol but Decreases 25Hydroxycholecalciferol in the Serum of Healthy Adults. J Nutr.
SUMIYOSHI, Y., HASHINE, K., KAKEHI, Y., YOSHIMURA, K., SATOU, T., KURUMA, H., NAMIKI,
S. & SHINOHARA, N. 2010. Dietary administration of mushroom mycelium extracts in
patients with early stage prostate cancers managed expectantly: a phase II study.
Japanese Journal of Clinical Oncology, 40, 967-972.
SUN, C., ROSENDAHL, A. H., WANG, X. D., WU, D. Q. & ANDERSSON, R. 2012.
Polysaccharide-K (PSK) in cancer - Old story, new possibilities? Current Medicinal
Chemistry, 19, 757-762.
SUN, J., WANG, H. X. & NG, T. B. 2011. Isolation of a laccase with HIV-1 reverse transcriptase
inhibitory activity from fresh fruiting bodies of the Lentinus edodes (Shiitake mushroom).
Indian Journal of Biochemistry & Biophysics, 48, 88-94.
338
SUN, W., YU, J., SHI, Y. M., ZHANG, H., WANG, Y. & WU, B. B. 2010. Effects of Cordyceps
extract on cytokines and transcription factors in peripheral blood mononuclear cells of
asthmatic children during remission stage. Zhong Xi Yi Jie He Xue Bao, 8, 341-346.
SUNG PHIL, K., MI YOUNG, K., YONG HEE, C., JAE HO, K., SEOK HYUN, N. & FRIEDMAN, M.
2011. Mechanism of Hericium erinaceus (Yamabushitake) mushroom-induced apoptosis of
U937 human monocytic leukemia cells. Food & Function, 2, 348-356.
SUZUKI, S., KAWAMATA, T., OKADA, Y., KOBAYASHI, T., NAKAMURA, T. & HORI, T. 2011.
Filtrate of Phellinus linteus broth culture reduces infarct size significantly in a rat model of
permanent focal cerebral ischemia. Evidence-Based Complementary and Alternative
Medicine, 1-7.
TAKAKU, T., KIMURA, Y. & OKUDA, H. 2001. Isolation of an antitumor compound from Agaricus
blazei Murill and its mechanism of action. Journal of Nutrition, 131, 1409-1413.
TALPUR, N., ECHARD, B., DADGAR, A., AGGARWAL, S., ZHUANG, C., BAGCHI, D. & PREUSS,
H. G. 2002. Effects of Maitake mushroom fractions on blood pressure of Zucker fatty rats.
Research Communications in Molecular Pathology and Pharmacology, 112, 68-82.
TAMBEKAR, D. H., SONAR, T. P., KHODKE, M. V. & KHANTE, B. S. 2006. The novel
antibacterials from two edible mushrooms: Agaricus bisporus and Pleurotus sajor caju.
International Journal of Pharmacology, 2, 582-585.
TANAKA, H., TSUNEMATSU, K., NAKAMURA, N., SUZUKI, K., TANAKA, N., TAKEYA, I., SAIKAI,
T. & ABE, S. 2004. Successful treatment of hypersensitivity pneumonitis caused by Grifola
frondosa (Maitake) mushroom using a HFA-BDP extra-fine aerosol. Internal Medicine, 43,
737-740.
TANAKA, K., ISHIKAWA, S., MATSUI, Y., TAMESADA, M., HARASHIMA, N. & HARADA, M. 2011.
Oral ingestion of Lentinula edodes mycelia extract inhibits B16 melanoma growth via
mitigation of regulatory T cell-mediated immunosuppression. Cancer Sci, 102, 516-21.
TAO, Y. Z., ZHANG, L. & CHEUNG, P. C. K. 2006. Physicochemical properties and antitumor
activities of water-soluble native and sulfated hyperbranched mushroom polysaccharides.
Carbohydrate Research, 341, 2261-2269.
TARVAINEN, K., SALONEN, J. P., KANERVA, L., ESTLANDER, T., KESKINEN, H. &
RANTANEN, T. 1991. Allergy and toxicodermia from shiitake mushrooms. Journal of the
American Academy of Dermatology, 24, 64-6.
TEICHMANN, A., DUTTA, P. C., STAFFAS, A. & JAGERSTAD, M. 2007. Sterol and vitamin D-2
concentrations in cultivated and wild grown mushrooms: Effects of UV irradiation. LWTFood Science and Technology, 40, 815-822.
THOMPSON, I. J., OYSTON, P. C. & WILLIAMSON, D. E. 2010. Potential of the beta-glucans to
enhance innate resistance to biological agents. Expert Rev Anti Infect Ther, 8, 339-52.
THYAGARAJAN, A., JEDINAK, A., HAI, N., TERRY, C., BALDRIDGE, L. A., JIAHUA, J. & SILVA,
D. 2010. Triterpenes from Ganoderma lucidum induce autophagy in colon cancer through
the inhibition of p38 mitogen-activated kinase (p38 MAPK). Nutrition and Cancer, 62, 630640.
THYAGARAJAN, A., JIANG, J., HOPF, A., ADAMEC, J. & SLIVA, D. 2006. Inhibition of oxidative
stress-induced invasiveness of cancer cells by Ganoderma lucidum is mediated through
the suppression of interleukin-8 secretion. International Journal of Molecular Medicine, 18,
657-664.
339
THYAGARAJAN, A., ZHU, J. & SLIVA, D. 2007. Combined effect of green tea and Ganoderma
lucidum on invasive behavior of breast cancer cells. International Journal of Oncology, 30,
963-969.
TOTH, B., COLES, M. & TALMADGE, J. 2007. Inhibition of intestinal cancer by VPS extract of the
Coriolus Versicolor mushroom in C57bl/6j-Apc(Min) mice. FASEB Journal, 21, A756.
TOTH, B., ERICKSON, J. & GANNETT, P. 1997. Lack of carcinogenesis by the baked mushroom
Agaricus bisporus in mice: different feeding regimen. In Vivo, 11, 227-231.
TSAI, S. Y., HUANG, S. J., LO, S. H. & MAU, J. L. 2008. Antioxidant properties of several culinarymedicinal mushrooms during postharvest storage. International Journal of Medicinal
Mushrooms, 10, 245-253.
TSAI, S. Y., HUANG, S. J., LO, S. H., WU, T. P., LIAN, P. Y. & MAU, J. L. 2009. Flavour
components and antioxidant properties of several cultivated mushrooms. Food Chemistry,
113, 578-584.
TSAI, S. Y., TSAI, H. L. & MAU, J. L. 2007. Antioxidant properties of Agaricus Blazei, Agrocybe
Cylindracea, and Boletus Edulis. LWT-Food Science and Technology, 40, 1392-1402.
TSUCHIDA, K., AOYAGI, Y., ODANI, S., MITA, T. & ISEMURA, M. 1995. Isolation of a novel
collagen-binding protein from the mushroom, Hypsizigus marmoreus, which inhibits the
Lewis lung carcinoma cell adhesion to type IV collagen. Journal of Biological Chemistry,
270, 1481-1484.
TSUJI, T., DU, W., NISHIOKA, T., CHEN, L., YAMAMOTO, D. & CHEN, C. Y. 2010. Phellinus
linteus extract sensitizes advanced prostate cancer cells to apoptosis in athymic nude
mice. PLoS One, 5, e9885.
TSUSHIMA, K., FURUYA, S., YOSHIKAWA, S., YASUO, M., YAMAZAKI, Y., KOIZUMI, T.,
FUJIMOTO, K. & KUBO, K. 2006. Therapeutic effects for hypersensitivity pneumonitis
induced by Japanese mushroom (Bunashimeji). American Journal of Industrial Medicine,
49, 826-835.
TZI, B. N., WANG, H. & WAN, D. C. C. 2006. Polysaccharopeptide from the Turkey Tail fungus
Trametes versicolor (L.:Fr.) pilat inhibits human immunodeficiency virus type 1 reverse
transciptase and protease. International Journal of Medicinal Mushrooms, 8, 39-43.
UKAWA, Y., ANDOU, M., FURUICHI, Y., KOKEAN, Y., NISHII, T. & HISAMATSU, M. 2001a.
Angiotensin I-converting enzyme inhibitory activity and antitumor activity of Hatakeshimeji
(Lyophyllum Decastes Sing.). Journal of the Japanese Society for Food Science and
Technology-Nippon Shokuhin Kagaku Kogaku Kaishi, 48, 58-63.
UKAWA, Y., ANDOU, M., FURUICHI, Y., KOKEAN, Y., NISHII, T. & HISAMATSU, M. 2001b.
Hypocholesterolemic activity of Hatakeshimeji (Lyophyllum Decastes Sing.) mushroom in
rats. Journal of the Japanese Society for Food Science and Technology-Nippon Shokuhin
Kagaku Kogaku Kaishi, 48, 520-525.
UKAWA, Y., KOJIMA, Y., SOMA, K., MISHIMA, T. & HISAMATSU, M. 2007. Safety evaluation of
hot-water extract of Hatake-Shimeji (Lyophyllum Decastes Sing.). Journal of the Japanese
Society for Food Science and Technology-Nippon Shokuhin Kagaku Kogaku Kaishi, 54,
133-137.
ULBRICHT, C., WEISSNER, W., BASCH, E., GIESE, N., HAMMERNESS, P., RUSIE-SEAMON,
E., VARGHESE, M. & WOODS, J. 2009. Maitake mushroom (Grifola frondosa): systematic
review by the natural standard research collaboration. J Soc Integr Oncol, 7, 66-72.
URBAIN, P., SINGLER, F., IHORST, G., BIESALSKI, H. K. & BERTZ, H. 2011. Bioavailability of
vitamin D(2) from UV-B-irradiated button mushrooms in healthy adults deficient in serum
340
25-hydroxyvitamin D: a randomized controlled trial. European Journal of Clinical Nutrition,

65, 965-971.
VENTURINI, M. E., RIVERA, C. S., GONZALEZ, C. & BLANCO, D. 2008. Antimicrobial activity of
extracts of edible wild and cultivated mushrooms against foodborne bacterial strains.
Journal of Food Protection, 71, 1701-1706.
VETTER, J. 1995. Mineral and amino acid contents of edible, cultivated shii-take mushrooms
(Lentinus edodes). Zeitschrift fuer Lebensmittel-Untersuchung und Forschung, 201, 17-19.
VETTER, J. & LELLEY, J. 2004. Selenium level of the cultivated mushroom Agaricus bisporus.
Acta Alimentaria, 33, 297-301.
VOLMAN, J. J., HELSPER, J., WEI, S., BAARS, J. J. P., VAN GRIENSVEN, L., SONNENBERG,
A. S. M., MENSINK, R. P. & PLAT, J. 2010a. Effects of mushroom-derived beta-glucanrich polysaccharide extracts on nitric oxide production by bone marrow-derived
macrophages and nuclear factor-kappa B transactivation in Caco-2 reporter cells: Can
effects be explained by structure? Molecular Nutrition & Food Research, 54, 268-276.
VOLMAN, J. J., MENSINK, R. P., VAN GRIENSVEN, L. J. & PLAT, J. 2010b. Effects of alphaglucans from Agaricus bisporus on ex vivo cytokine production by LPS and PHA-stimulated
PBMCs; a placebo-controlled study in slightly hypercholesterolemic subjects. European
Journal of Clinical Nutrition, 64, 720-726.
WACHTEL-GALOR, S., TOMLINSON, B. & BENZIE, I. F. F. 2004. Ganoderma lucidum ('Lingzhi'),
a Chinese medicinal mushroom: biomarker responses in a controlled human
supplementation study. British Journal of Nutrition, 91, 263-269.
WACHTEL-GALOR, S., WONG, W., CHOI, S. & BENZIE, I. F. F. 2010. Antioxidant power and
DNA repair effects of Lingzhi or Reishi medicinal mushroom, Ganoderma lucidum
(W.Curt.:Fr.) P. Karst. (Aphyllophoromycetideae), in human acute post-ingestion study.
WAN, J. M.-F., SIT, W.-H. & LOUIE, J. C.-Y. 2008. Polysaccharopeptide enhances the anticancer
activity of doxorubicin and etoposide on human breast cancer cells ZR-75-30. International
Journal of Oncology, 32, 689-699.
WANG, C., NG, T., LI, L., FANG, J., JIANG, Y., WEN, T., QIAO, W., LI, N. & LIU, F. 2011. Isolation
of a polysaccharide with antiproliferative, hypoglycemic, antioxidant and HIV-1 reverse
transcriptase inhibitory activities from the fruiting bodies of the abalone mushroom
Pleurotus abalonus. Journal of Pharmacy and Pharmacology, 63, 825-832.
WANG, G., DONG, L., ZHANG, Y., JI, Y., XIANG, W. & ZHAO, M. 2012a. Polysaccharides from
Phellinus linteus inhibit cell growth and invasion and induce apoptosis in HepG2 human
hepatocellular carcinoma cells. Biologia (Bratislava), 67, 247-254.
WANG, G. J., TSAI, T. H., CHANG, T. T., CHOU, C. J. & LIN, L. C. 2009. Lanostanes from
Phellinus igniarius and their iNOS inhibitory activities. Planta Med, 75, 1602-7.
WANG, H., GAO, J. & NG, T. B. 2000. A new lectin with highly potent antihepatoma and
antisarcoma activities from the oyster mushroom Pleurotus ostreatus. Biochemical and
Biophysical Research Communications, 275, 810-816.
WANG, H. X. & NG, T. B. 2000. Isolation of a novel ubiquitin-like protein from Pleurotus ostreatus
mushroom with anti-human immunodeficiency virus, translation-inhibitory, and
ribonuclease activities. Biochemical and Biophysical Research Communications, 276, 587593.
WANG, H. X. & NG, T. B. 2001. Examination of lectins, polysaccharopeptide, polysaccharide,
alkaloid, coumarin and trypsin inhibitors for inhibitory activity against human
341
immunodeficiency virus reverse transcriptase and glycohydrolases. Planta Medica, 67,

669-672.
WANG, J., LIU, Y. M., CAO, W., YAO, K. W., LIU, Z. Q. & GUO, J. Y. 2012b. Anti-inflammation and
antioxidant effect of Cordymin, a peptide purified from the medicinal mushroom Cordyceps
sinensis, in middle cerebral artery occlusion-induced focal cerebral ischemia in rats. Metab
Brain Dis, 27, 159-65.
WANG, J. C., HU, S. H., SU, C. H. & LEE, T. M. 2001. Antitumor and immunoenhancing activities
of polysaccharide from culture broth of Hericium spp. Kaohsiung Journal of Medical
Sciences, 17, 461-467.
WANG, J. C. Y., HU, S. H., WANG, J. T., CHEN, K. S. & CHIA, Y. C. 2005. Hypoglycemic effect of
extract of Hericium Erinaceus. Journal of the Science of Food and Agriculture, 85, 641646.
WANG, L., HA, C.-L., CHENG, T.-L., CHENG, S.-Y., LIAN, T.-W. & WU, M.-J. 2008. Oral
administration of submerged cultivated Grifola frondosa enhances phagocytic activity in
normal mice. Journal of Pharmacy and Pharmacology, 60, 237-243.
WANG, L. C., WANG, S. E., WANG, J. J., TSAI, T. Y., LIN, C. H., PAN, T. M. & LEE, C. L. 2012c.
In vitro and in vivo comparisons of the effects of the fruiting body and mycelium of Antrodia
camphorata against amyloid beta-protein-induced neurotoxicity and memory impairment.
Appl Microbiol Biotechnol, 94, 1505-19.
WANG, L. H., TSAI, S. J. & LIN, S. Y. 2004. Aqueous extract from Taiwanese Agrocybe
Cylindracea strain B protects DNA against center .OH-mediated strand breaks. Journal of
Food and Drug Analysis, 12, 277-285.
WASONGA, C. G., OKOTH, S. A., MUKURIA, J. C. & OMWANDHO, C. O. 2008. Mushroom
polysaccharide extracts delay progression of carcinogenesis in mice. Journal of
Experimental Therapeutics and Oncology, 7, 147-152.
WATANABE, T., YAMADA, T., ISHI, S., MAZUMDER, T. K., NAGAI, S. & TSUJI, K. 2002. Effect of
autolyzed-Shiitake (Lentinus Edodes) on blood pressure and serum fat levels in
spontaneously hypertensive rats. Journal of the Japanese Society for Food Science and
Technology-Nippon Shokuhin Kagaku Kogaku Kaishi, 49, 662-669.
WEI, S., HELSPER, J. P. F. G. & VAN GRIENSVEN, L. J. L. D. 2008. Phenolic compounds present
in medicinal mushroom extracts generate reactive oxygen species in human cells in vitro.
WEIGAND-HELLER, A. J., KRIS-ETHERTON, P. M. & BEELMAN, R. B. 2012. The bioavailability
of ergothioneine from mushrooms (Agaricus bisporus) and the acute effects on antioxidant
capacity and biomarkers of inflammation. Prev Med, 54 Suppl, S75-8.
WENG, C.-J., CHAU, C.-F., CHEN, K.-D., CHEN, D.-H. & YEN, G.-C. 2007. The anti-invasive
effect of lucidenic acids isolated from a new Ganoderma lucidum strain. Molecular Nutrition
& Food Research, 51, 1472-1477.
WENG, C. J. & YEN, G. C. 2010. The in vitro and in vivo experimental evidences disclose the
chemopreventive effects of Ganoderma lucidum on cancer invasion and metastasis.
Clinical & Experimental Metastasis, 27, 361-369.
WENNER, C. A., MARTZEN, M. R., LU, H., VERNERIS, M. R., WANG, H. & SLATON, J. W. 2012.
Polysaccharide-K augments docetaxel-induced tumor suppression and antitumor immune
response in an immunocompetent murine model of human prostate cancer. International
Journal of Oncology, 40, 905-913.
342
WHITE, R. W. D., HACKMAN, R. M., SOARES, S. E., BECKETT, L. A. & SUN, B. X. 2002. Effects
of a mushroom mycelium extract on the treatment of prostate cancer. Urology, 60, 640644.
WONG, C. K., BAO, Y. X., WONG, E. L. Y., LEUNG, P. C., FUNG, K. P. & LAM, C. W. K. 2005.
Immunomodulatory activities of Yunzhi and Danshen in post-treatment breast cancer
patients. American Journal of Chinese Medicine, 33, 381-395.
WONG, J. H., NG, T. B., JIANG, Y., LIU, F., SZE, S. C. & ZHANG, K. Y. 2010. Purification and
characterization of a Laccase with inhibitory activity toward HIV-1 reverse transcriptase
and tumor cells from an edible mushroom (Pleurotus cornucopiae). Protein Pept Lett, 17,
1040-7.
WONG, K.-H., VIKINESWARY, S., ABDULLAH, N., NAIDU, M. & KEYNES, R. 2007. Activity of
aqueous extracts of lion's mane mushroom Hericium erinaceus (Bull.: Fr.) Pers.
(Aphyllophoromycetideae) on the neural cell line NG108-15. International Journal of
WONG, K., LAI, C. K. M. & CHEUNG, P. C. K. 2011. Immunomodulatory activities of mushroom
sclerotial polysaccharides. Food Hydrocolloids, 25, 150-158.
WONG, K. L., CHAO, H. H., CHAN, P., CHANG, L. P. & LIU, C. F. 2004. Antioxidant activity of
Ganoderma lucidum in acute ethanol-induced heart toxicity. Phytotherapy Research, 18,
1024-1026.
WU, C., LIN, T., HSU, H., SHEU, F., HO, C. & CHEN, E. I. T. 2011a. Ling Zhi-8 mediates p53dependent growth arrest of lung cancer cells proliferation via the ribosomal protein S7MDM2-p53 pathway. Carcinogenesis, 32, 1890-1896.
WU, D., PAE, M., REN, Z., GUO, Z., SMITH, D. & MEYDANI, S. N. 2007a. Dietary
supplementation with white button mushroom enhances natural killer cell activity in
C57BL/6 mice. Journal of Nutrition, 137, 1472-1477.
WU, D. Y., HAN, S. N., BRONSON, R. T., SMITH, D. E. & MEYDANI, S. N. 1998. Dietary
supplementation with mushroom-derived protein-bound glucan does not enhance immune
function in young and old mice. Journal of Nutrition, 128, 193-197.
WU, G. S., LU, J. J., GUO, J. J., LI, Y. B., TAN, W., DANG, Y. Y., ZHONG, Z. F., XU, Z. T., CHEN,
X. P. & WANG, Y. T. 2012. Ganoderic acid DM, a natural triterpenoid, induces DNA
damage, G1 cell cycle arrest and apoptosis in human breast cancer cells. Fitoterapia, 83,
408-14.
WU, H. Y., ZHANG, Q. X. & LEUNG, P. H. 2007b. Inhibitory effects of ethyl acetate extract of
Cordyceps Sinensis mycelium on various cancer cells in culture and B16 melanoma in
C57bl/6 mice. Phytomedicine, 14, 43-49.
WU, M. F., CHEN, Y. L., LEE, M. H., SHIH, Y. L., HSU, Y. M., TANG, M. C., LU, H. F., TANG, N.
Y., YANG, S. T., CHUEH, F. S. & CHUNG, J. G. 2011b. Effect of Agaricus blazei Murrill
extract on HT-29 human colon cancer cells in SCID mice in vivo. In Vivo, 25, 673-677.
WU, Q., TAN, Z., LIU, H., GAO, L., WU, S., LUO, J., ZHANG, W., ZHAO, T., YU, J. & XU, X. 2010.
Chemical characterization of Auricularia auricula polysaccharides and its pharmacological
effect on heart antioxidant enzyme activities and left ventricular function in aged mice.
International Journal of Biological Macromolecules, 46, 284-288.
XIE, J. T., WANG, C. Z., WICKS, S., YIN, J. J., KONG, J., LI, J., LI, Y. C. & YUAN, C. S. 2006.
Ganoderma lucidum extract inhibits proliferation of SW 480 human colorectal cancer cells.
Experimental Oncology, 28, 25-29.
343
XU, L., WANG, H. & NG, T. 2012a. A laccase with HIV-1 reverse transcriptase inhibitory activity
from the broth of mycelial culture of the mushroom Lentinus tigrinus. J Biomed Biotechnol,
2012, 536725.
XU, M. L., CHOI, J. Y., JEONG, B. S., LI, G., LEE, K. R., LEE, C. S., WOO, M. H., LEE, E. S.,
JAHNG, Y., CHANG, H. W., LEE, S. H. & SON, J. K. 2007. Cytotoxic constituents isolated
from the fruit bodies of Hypsizigus marmoreus. Archives of Pharmacology Research, 30,
28-33.
XU, T., BEELMAN, R. B. & LAMBERT, J. D. 2012b. The cancer preventive effects of edible
mushrooms. Anticancer Agents Med Chem.
XU, X., PAN, C., ZHANG, L. & ASHIDA, H. 2011a. Immunomodulatory beta-glucan from Lentinus
edodes activates mitogen-activated protein kinases and nuclear factor-kappaB in murine
RAW 264.7 macrophages. J Biol Chem, 286, 31194-8.
XU, X., PANG, C., YANG, C., ZHENG, Y., XU, H., LU, Z. & XU, Z. 2010. Antihyperglycemic and
antilipidperoxidative effects of polysaccharides extracted from medicinal mushroom chaga,
Inonotus obliquus (Pers.: Fr.) Pilat (Aphyllophoromycetideae) on alloxan-diabetes mice.
XU, X. F., YAN, H. D., CHEN, J. & ZHANG, X. W. 2011b. Bioactive proteins from mushrooms.
Biotechnology Advances, 29, 667-674.
YAMAC, M., KANBAK, G., ZEYTINOGLU, M., BAYRAMOGLU, G., SENTURK, H. & UYANOGLU,
M. 2008. Hypoglycemic effect of Lentinus Strigosus (Schwein.) Fr. Crude
exopolysaccharide in Streptozotocin-induced diabetic rats. Journal of Medicinal Food, 11,
513-517.
YAMAC, M., KANBAK, G., ZEYTINOGLU, M., SENTURK, H., BAYRAMOGLU, G.,
DOKUMACIOGLU, A. & GRIENSVEN, L. J. L. D. V. 2010. Pancreas protective effect of
button mushroom Agaricus bisporus (J.E. Lange) imbach (Agaricomycetidae) extract on
rats with streptozotocin-induced diabetes. International Journal of Medicinal Mushrooms,
12, 379-389.
YAMAGUCHI, N., YOSHIDA, J., REN, L. J., CHEN, H., MIYAZAWA, Y., FUJII, Y., HUANG, Y. X.,
TAKAMURA, S., SUZUKI, S., KOSHIMURA, S. & ET, A. L. 1990. Augmentation of various
immune reactivities of tumor-bearing hosts with an extract of Cordyceps sinensis.
Biotherapy, 2, 199-205.
YAMAGUCHI, Y., MIYAHARA, E. & HIHARA, J. 2011. Efficacy and safety of orally administered
Lentinula edodes mycelia extract for patients undergoing cancer chemotherapy: a pilot
study. Am J Chin Med, 39, 451-459.
YAMANAKA, D., MOTOI, M., ISHIBASHI, K. I., MIURA, N. N., ADACHI, Y. & OHNO, N. 2011.
Effect of Agaricus brasiliensis-derived cold water extract on Toll-like receptor 2-dependent
cytokine production in vitro. Immunopharmacol Immunotoxicol.
YANG, B.-K., PARK, J.-B. & SONG, C.-H. 2002a. Hypolipidemic effect of exo-polymer produced in
submerged mycelial culture of five different mushrooms. Journal of Microbiology and
YANG, B. K., JEONG, S. C. & SONG, C. H. 2002b. Hypolipidemic effect of exo- and endobiopolymers produced from submerged mycelial culture of Ganoderma Lucidum in rats.
Journal of Microbiology and Biotechnology, 12, 872-877.
YANG, B. K., KIM, D. H., JEONG, S. C., DAS, S., CHOI, Y. S., SHIN, J. S., LEE, S. C. & SONG, C.
H. 2002c. Hypoglycemic effect of a Lentinus edodes exo-polymer produced from a
submerged mycelial culture. Bioscience, Biotechnology and Biochemistry, 66, 937-942.
344
YANG, B. K., PARK, J. B. & SONG, C. H. 2003. Hypolipidemic effect of an exo-biopolymer

produced from a submerged mycelial culture of Hericium erinaceus. Bioscience
Biotechnology and Biochemistry, 67, 1292-1298.
YANG, B. K., WILSON, M. A., CHO, K. Y. & SONG, C. H. 2004. Hypoglycemic effect of exo- and
endo-biopolymers produced by submerged mycelial culture of Ganoderma Lucidum in
streptozotocin-induced diabetic rats. Journal of Microbiology and Biotechnology, 14, 972977.
YANG, H. L., KUO, Y. H., TSAI, C. T., HUANG, Y. T., CHEN, S. C., CHANG, H. W., LIN, E., LIN,
W. H. & HSEU, Y. C. 2011. Anti-metastatic activities of Antrodia camphorata against
human breast cancer cells mediated through suppression of the MAPK signaling pathway.
Food Chem Toxicol, 49, 290-298.
YANG, N., LI, D. F., FENG, L., XIANG, Y., LIU, W., SUN, H. & WANG, D. C. 2009. Structural basis
for the tumor cell apoptosis-inducing activity of an antitumor lectin from the edible
mushroom Agrocybe aegerita. J Mol Biol, 387, 694-705.
YANG, N., TONG, X., XIANG, Y., ZHANG, Y., LIANG, Y., SUN, H. & WANG, D. C. 2005. Molecular
character of the recombinant antitumor lectin from the edible mushroom Agrocybe
aegerita. Journal of Biochemistry, 138, 145-150.
YASUKAWA, K., AOKI, T., TAKIDO, M., IKEKAWA, T., SAITO, H. & MATSUZAWA, T. 1994.
Inhibitory effects of ergosterol isolated from the edible mushroom Hypsizigus-Marmoreus
on TPA-induced inflammatory ear edema and tumor promotion in mice. Phytotherapy
Research, 8, 10-13.
YIN, Z. N., FUJII, H. & WALSHE, T. 2010. Effects of active hexose correlated compound on
frequency of CD4(+) and CD8(+) T cells producing interferon-gamma and/or tumor
necrosis factor-alpha in healthy adults. Human Immunology, 71, 1187-1190.
YOON, S. J., YU, M. A., PYUN, Y. R., HWANG, J. K., CHU, D. C., JUNEJA, L. R. & MOURAO, P.
A. 2003. The nontoxic mushroom Auricularia auricula contains a polysaccharide with
anticoagulant activity mediated by antithrombin. Thrombosis Research, 112, 151-158.
YOSHIMOTO, H., EGUCHI, F., HIGAKI, M. & OHGA, S. 2005. Influence of culture medium
components on the pharmacological effects of Agaricus Blazei. Mokuzai Gakkaishi, 51,
387-393.
YOSHIMURA, K., KAMOTO, T., OGAWA, O., MATSUI, S., TSUCHIYA, N., TADA, H., MURATA,
K., HABUCHI, T. & FUKUSHIMA, M. 2010. Medical mushrooms used for biochemical
failure after radical treatment for prostate cancer: An open-label study. International
Journal of Urology, 17, 548-554.
YOSHIOKA, Y., TAMESADA, M. & TOMI, H. 2010. A repeated dose 28-day oral toxicity study of
extract from cultured Lentinula edodes mycelia in Wistar rats. J Toxicol Sci, 35, 785-791.
YOUN, M. A., KIM, J. K., PARK, S. Y., KIM, Y., KIM, S. J., LEE, J. S., CHAI, K. Y., KIM, H. J., CUI,
M. X., SO, H. S., KIM, K. Y. & PARK, R. 2008. Chaga mushroom (Inonotus Obliquus)
induces G(0)/G(1) arrest and apoptosis in human hepatoma HepG2 cells. World Journal of
Gastroenterology, 14, 511-517.
YU, C. H., KAN, S. F., SHU, C. H., LU, T. J., SUN-HWANG, L. & WANG, P. S. 2009a. Inhibitory
mechanisms of Agaricus blazei Murill on the growth of prostate cancer in vitro and in vivo.
Journal of Nutritional Biochemistry, 20, 753-764.
YU, L., FERNIG, D. G., SMITH, J. A., MILTON, J. D. & RHODES, J. M. 1993. Reversible inhibition
of proliferation of epithelial cell lines by Agaricus bisporus (edible mushroom) lectin.
345
YU, L. G., FERNIG, D. G. & RHODES, J. M. 2000. Intracellular trafficking and release of intact
edible mushroom lectin from HT29 human colon cancer cells. European Journal of
YU, M. Y., XU, X. Y., QING, Y., LUO, X., YANG, Z. R. & ZHENG, L. Y. 2009b. Isolation of an antitumor polysaccharide from Auricularia Polytricha (Jew's Ear) and its effects on
macrophage activation. European Food Research and Technology, 228, 477-485.
YU, Z. H., YIN, L. H., QIAN, Y. & YAN, L. 2009c. Effect of Lentinus Edodes polysaccharide on
oxidative stress, immunity activity and oral ulceration of rats stimulated by phenol.
Carbohydrate Polymers, 75, 115-118.
YUE, G. G. L., FUNG, K. P., TSE, G. M. K., LEUNG, P. C. & LAU, C. B. S. 2006. Comparative
Studies of Various Ganoderma Species and Their Different Parts With Regard to Their
Antitumor and Immunomodulating Activities in Vitro. Journal of Alternative and
Complementary Medicine, 12, 777-789.
YUEN, J. W. & GOHEL, M. D. 2005. Anticancer effects of Ganoderma lucidum: a review of
scientific evidence. Nutrition and Cancer, 53, 11-17.
YUMINAMOCHI, E., KOIKE, T., TAKEDA, K., HORIUCHI, I. & OKUMURA, K. 2007. Interleukin-12and interferon-gamma-mediated natural killer cell activation by Agaricus blazei Murill.
Immunology, 121, 197-206.
ZAURA, E., BUIJS, M. J., HOOGENKAMP, M. A., CIRIC, L., PAPETTI, A., SIGNORETTO, C.,
STAUDER, M., LINGSTROM, P., PRATTEN, J., SPRATT, D. A. & WILSON, M. 2011. The
effects of fractions from shiitake mushroom on composition and cariogenicity of dental
plaque microcosms in an in vitro caries model. J Biomed Biotechnol, 2011, 135034.
ZHANG, M., HUANG, J., XIE, X. & HOLMAN, C. D. J. 2009. Dietary intakes of mushrooms and
green tea combine to reduce the risk of breast cancer in Chinese women. International
Journal of Cancer, 124, 1404-1408.
ZHANG, W. Y., YANG, J. Y., CHEN, J. P., HOU, Y. Y. & HAN, X. D. 2005. Immunomodulatory and
Antitumour Effects of an Exopolysaccharide Fraction From Cultivated Cordyceps Sinensis
(Chinese Caterpillar Fungus) on Tumour-Bearing Mice. Biotechnology and Applied
ZHANG, Y., MILLS, G. L. & NAIR, M. G. 2002. Cyclooxygenase inhibitory and antioxidant
compounds from the mycelia of the edible mushroom Grifola frondosa. Journal of
ZHAO, L., ZHAO, G., HUI, B., MAO, Z., TONG, J. & HU, X. 2004. Effect of selenium on increasing
the antioxidant activity of protein extracts from a selenium-enriched mushroom species of
the Ganoderma genus. Journal of Food Science, 69, C184-C188.
ZHAO, L., ZHAO, G. H., DU, M., ZHAO, Z. D., XIAO, L. X. & HU, X. S. 2008. Effect of selenium on
increasing free radical scavenging activities of polysaccharide extracts from a Se-enriched
mushroom species of the genus Ganoderma. European Food Research and Technology,
226, 499-505.
ZHAO, S., YE, G., FU, G., CHENG, J., YANG, B. B. & PENG, C. 2011. Ganoderma lucidum exerts
anti-tumor effects on ovarian cancer cells and enhances their sensitivity to cisplatin.
ZHE, J., TANG, Q., ZHANG, J., YANG, Y., LIU, Y. & PAN, Y. 2011. Immunomodulation of bone
marrow macrophages by GLIS, a proteoglycan fraction from Lingzhi or Reishi medicinal
mushroom Ganoderma lucidium (W.Curt.:Fr.) P. Karst. International Journal of Medicinal
Mushrooms, 13, 441-448.
346
ZHONG, M., TAI, A. & YAMAMOTO, I. 2005. In vitro augmentation of natural killer activity and
interferon-gamma production in murine spleen cells with Agaricus blazei fruiting body
fractions. Bioscience Biotechnology and Biochemistry, 69, 2466-2469.
ZHOU, L., ZHANG, Q., ZHANG, Y., LIU, J. & CAO, Y. 2009. The shiitake mushroom-derived
immuno-stimulant lentinan protects against murine malaria blood-stage infection by
evoking adaptive immune-responses. International Immunopharmacology, 9, 455-462.
ZHOU, S., GAO, Y. & CHAN, E. 2005. Clinical trials for medicinal mushrooms: Experience with
Ganoderma lucidum (W.Curt.:Fr.) Lloyd (Lingzhi Mushroom). International Journal of
ZHOU, X. W., JIANG, H., LIN, J. & TANG, K. X. 2007. Cytotoxic activities of Coriolus Versicolor
(Yunzhi) extracts on human liver cancer and breast cancer cell line. African Journal of
ZILIOTTO, L., BARBISAN, L. F. & RODRIGUES, M. A. M. 2008. Lack of chemoprevention of
dietary Agaricus Blazei against rat colonic aberrant crypt foci. Human & Experimental
Toxicology, 27, 505-511.
ZILIOTTO, L., PINHEIRO, F., BARBISAN, L. F. & RODRIGUES, M. A. M. 2009. Screening for in
vitro and in vivo antitumor activities of the mushroom Agaricus blazei. Nutrition and
Cancer, 61, 245-250.
347
Key to Reference Sources

Note: The most recent national nutrient databases available were used.
(Can) Canada. Health Canada. Canadian Nutrient File. Version 2007b. Available at http://www.hc-sc.gc.ca/fn-an/nutrition/fiche-nutridata/cnf_aboutus-aproposdenous_fcen-eng.php. Accessed 23 June, 2012.
(Den) Denmark. National Food Institute. Danish Food Composition Databank. Available at http://www.foodcomp.dk/fcdb. Accessed 12 June,
2012.
(Fin) Finland. National Public Health Institute. At http://wwwfineli.fi Accessed on 12 June, 2012.
(Aus) Food Standards Australia New Zealand. NUTTAB 2010 Online Version. Available at
http://www.foodstandards.gov.au/monitoringandsurveillance/nuttab2006/onlineversionintroduction/onlineversion.cfm? Accessed 12 June, 2012
Goyal R, Grewal RB, Goyal RK. Nutritional attributes of Agaricus bisporus and Pleurotus sojor caju mushrooms. Nutr Health 2006; 18 (2): 179184.
(Jap) Japan Resources Council of the Science and Technology Agency. Standard Table of Food Composition in Japan.- 5th rev ed- Accessed
on Sugiyama Jogakuen University, Department of Food and Nutrition School of Life Sciences at http://database.food.sugiyama-u.ac.jp.
Accessed on 12 June, 2012.
(UK) United Kingdom Foods Standards Agency. McCance and Widdowsons The Composition of Foods -6th Summary Ed- Food Standards
Agency, Royal Society of Chemistry, Institute of Food Research, Cambridge, RSC 2002.
252
Mattila, P., Konko, K., Eurola, M., Pihalva, J-M., Astola, J., Vahterist, L., Huetaniemi, V., Kumpulainen, J., Valtonen, M and Piironen, V.
Contents of vitamins, mineral elements, and some phenolic compounds in cultivated mushrooms. J Agric Food Chem 2001 49: 2343-2348.
Mattila, P., Salo-Vaananen, P., Konko, K., Aro, H., Jalava, T. Basic composition and amino acid contents of mushrooms cultivated in Finland. J
Agric Food Chem 2002; 50: 6419-6422.
(Ger) Souci, S.W, Fachmann, W. and Kraut, H. Food Composition and Nutrition tables.-5th ed Stuttgart ,Med Pharm and CRC Press, 1994.
(This edition compiled by Scherz, H and Senser, F.)
(USDA) U.S. Department of Agriculture, Agricultural Research Service Nutrient Data Laboratory.. USDA National Nutrient Database for
Standard Reference, Release 24, 2011. Available at Nutrient Data Laboratory Home Page, http://www.ars.usda.gov/ba/bhnrc/ndl Accessed 24
May, 2012.
Log Grown. Data from http://shiitakemushroomlog.com/facts&nutrition.html (Actual source of calculations not given) Accessed on 23 May,
2012.
253
Summary Tables for RAW COMMON MUSHROOMS (Agaricus bisporus) providing >10% RDI/AI of key vitamins/100g
Riboflavin
(B2) (mg)
Males
19-70
years
Males
over
70
years
Females
19-70
years
Females
over 70
years
Niacin
equivalents
(B3) (mg)
Males
19
years
and
over
Females
19 years
and
over
Folate
(mcg)
Males
19
years
and
over
Females
19 years
and
over
Vit
B6
(mg)
Males
19-50
years
Males
over
50
years
Females
19-50
years
Females
over 50
years
RDI
1.3
1.6
1.1
1.3
RDI
16
14
RDI
400
400
RDI
1.3
1.7
1.3
1.5
Agariscus bisporus
white (Matilla 2002)
0.39
30.0%
24.4%
35.5%
30.0%
3.3
20.6%
23.6%
36
Agariscus bisporus
brown (Matilla 2002)
0.33
25.4%
20.6%
30.0%
25.4%
4.1
25.6%
29.3%
46
0.402
30.9%
25.1%
36.5%
30.9%
3.607
22.5%
25.8%
17
0.31
23.8%
19.4%
28.2%
23.8%
3.2
20.0%
22.9%
44
13.8%
10.6%
13.8%
12.0%
13.8%
10.6%
13.8%
12.0%
Nutrient
Mushrooms white
Agaricus bisporus
(USDA)
Mushrooms common
(UK)
India (Goyal 2006)
Champignon fresh A.
bisporus (Fin)
Common mushroom
(Jap)
Mushroom Agaricus
bisporus (Den)
Mushroom Agaricus
bisporus SFK (Ger)
Mushroom Common
Agaricus bisporus
(Aust)
Mushroom, white, raw
(Can)
Mushroom Portabella
raw Agaricus bisporus
(USDA)
Mushroom Portabella
(Portobello), raw (Can)
Mushroom Brown
Italian or Crimini raw
Agaricus bisporus
(USDA)
Mushroom Brown
Italian (Crimini) raw
(Can)
Mushroom Portabella
exposed to UV light
raw A. bisporus
(USDA)
N/A
N/A
N/A
11.5%
11.5%
N/A
0.104
11.0%
11.0%
0.18
N/A
N/A
0.42
32.3%
26.3%
38.2%
32.3%
6.1
38.1%
43.6%
35
0.18
0.29
22.3%
18.1%
26.4%
22.3%
18.8%
21.4%
28
0.11
0.44
33.8%
27.5%
40.0%
33.8%
6.05
37.8%
43.2%
41
0.44
33.8%
27.5%
40.0%
33.8%
N/A
0.369
28.4%
23.1%
33.5%
28.4%
3.72
23.3%
0.402
30.9%
25.1%
36.5%
30.9%
4.19
0.13
10.0%
11.8%
10.0%
0.13
10.0%
11.8%
0.49
37.7%
30.6%
0.49
37.7%
30.6%
0.13
10.0%
10.3%
10.3%
0.06
N/A
0.065
26.6%
18
0.02
26.2%
29.9%
16
0.104
4.494
28.1%
32.1%
28
0.148
11.4%
11.4%
10.0%
4.494
28.1%
32.1%
22
0.148
11.4%
11.4%
44.5%
37.7%
3.8
23.8%
27.1%
25
0.11
44.5%
37.7%
3.8
23.8%
27.1%
14
0.11
11.8%
10.0%
4.494
28.1%
32.1%
28
0.148
11.4%
11.4%
254
Summary Table for RAW COMMON MUSHROOMS (Agaricus bisporus) providing >10% RDI/AI of key vitamins/100g
Pantothenic
acid (mg)
Males
19 years
and over
Females
19 years
and
over
Biotin
(mcg)
Males
19 years
and over
Females
19 years
and
over
Vit C
(mg)
Males
19
years
and
over
Females
19 years
and
over
Vit D
(mcg)
Males
19-50
years
Males
51-70
years
Males
over
70
years
Females
19-50
years
Females
51-70
years
Females
over 70
years
AI
AI
30
25
RDI
45
45
AI
10
15
10
15
20.0%
10.0%
20.0%
10.0%
38.8%
19.4%
12.9%
38.8%
19.4%
12.9%
224.0%
112.0%
74.7%
224.0%
112.0%
74.7%
Nutrient
Agariscus bisporus
white (Matilla 2002)
N/A
N/A
N/A
N/A
Agariscus bisporus
brown (Matilla 2002)
N/A
N/A
N/A
N/A
2.1
0.2
N/A
Mushrooms white
Agaricus bisporus
(USDA)
Mushrooms common
(UK)
India (Goyal 2006)
1.497
25.0%
37.4%
N/A
33.3%
50.0%
12
40.0%
48.0%
N/A
N/A
N/A
N/A
N/A
N/A
1.3
0.2
1
0
Champignon fresh A.
bisporus (Fin)
Common mushroom
(Jap)
Mushroom Agaricus
bisporus (Den)
1.54
25.7%
38.5%
N/A
33.3%
50.0%
16
53.3%
64.0%
3.1
Mushroom Agaricus
bisporus SFK (Ger)
2.1
35.0%
52.5%
16
53.3%
64.0%
4.9
Mushroom Common
Agaricus bisporus (Aust)
1.15
19.2%
28.8%
8.9
29.7%
35.6%
N/A
1.497
25.0%
37.4%
N/A
2.1
0.175
1.14
19.0%
28.5%
N/A
0.3
Mushroom Portabella
1.14
19.0%
28.5%
N/A
0.3
Mushroom Brown Italian

or Crimini raw Agaricus
bisporus (USDA)
1.5
25.0%
37.5%
N/A
0.1

(Crimini) raw (Can)
1.5
25.0%
37.5%
N/A
0.1
Mushroom Portabella
exposed to UV light raw
A. bisporus (USDA)
1.14
19.0%
28.5%
N/A
11.2
Mushroom, white, raw

(Can)
Mushroom Portabella
raw Agaricus bisporus
(USDA)
255
10.9%
10.9%
1.94
Table 1 Average24 %RDI/AI content for each Key Vitamin /100g

Vitamin
Average %
Recommended Dietary Intake
Riboflavin (B2)
M 25.8%
F 28.9%
1.3mg male 19-7 : 1.6mg men>70

1.1mg Female 19-70:1.3mg female>70
Niacin (B3)
M 26%
F 29.8%
16mg male 19 and over

14mg female 19 and over
Folate
M and F
10.9%
400mcg male and female 19 and over
Vitamin B6
M 11.9%
F 12.3%
1.3mg male 19-50 yrs : 1.7mg male >70

1.3 Females 19-50 : 1.5 female > 50 years
Pantothenic acid
M 25.3%
F 37.9%

Biotin
M 44.1%
F 52.9%

Vitamin C
M and F
10.9%
M and F 64%
45mg male and female 19 and over
Vitamin D
24
Comments
# > 10% RDI Provided by 15 of 16 mushrooms for M and F
Range male 19 and over 10-37.7%
Range female 19 and over 10-44.5%

Mushroom Brown Italian (Crimini) Raw (USDA) and (Can) providing the
greatest amount
#>10% RDI Provided for 14 of 16 for M and F
Range male 19 and over 18.8-38.1%
Range female 19 and over 21.4-43.6%

Champignion Fresh (A.Bisporus) (Fin) providing the greatest amount
# >10%RDI provided by 3 of 16 mushrooms for M and F
Range male and female 19 and over 10.3-11.5%

Agaricus bisporus brown (Matilla 2002) providing the greatest amount
#>10% RDI provided by 5 of the 16 for M and F
Range male 19 and over 10.6 -13.8%

Mushroom common (UK) and Champignion Fresh (A. Bisporus. (Fin)
providing the greatest amount
#>10% AI provided by 12 of the 16 for M and F
Range male 19 and over 19 35%

Mushroom Agaricus bisporus SFK (Ger) providing the greatest amount
#>10% AI provided by 4 of the 16 for M and F
Range male 19 and over 29.7 53.3%
Range female 19 and over 35.6 -64%

Mushroom agaricus bisporaus (Den) and Mushroom Agaricus Bisporus
SFK (Ger) providing the greatest amount
#>10% RDI provided by 1 of 14 mushrooms for M and F
10.9% Mushroom Agaricus Bisporus SFK (Ger)
5mcg Male and female 19-50:

10mcg male and female 51-70:
15mcg male and female >70
# >10% AI provided by 3 of 16 mushrooms for M and F
Range male and female 19 50: 20224%
Range male and female 51-70: 10112%
Range male and female 70 and over: 12.9-74.7%

Mushroom Portabella exposed to UV light raw A. bisporus (USDA)
providing the greatest amount at 11.2mcg/100g
Average values taken from mushroom data providing greater than or equal to 10%RDI/AI
256
Summary Table for RAW COMMON MUSHROOMS (Agaricus bisporus) providing >10% RDI/AI of key minerals /100g
Copper (mg)
Males
19
years
and
over
Females
19 years
and
over
Phosphorus
(mg)
Males
19
years
and
over
Females
19 years
and
over
Potassium
(mg)
Males
19
years
and
over
Females
19 years
and
over
AI
1.7
1.2
RDI
1000
1000
AI
3800
2800
Agariscus bisporus white

(Matilla 2002)
0.22
12.9%
18.3%
98
Agariscus bisporus brown

(Matilla 2002)
0.27
15.9%
22.5%
101
Mushrooms white Agaricus

bisporus (USDA)
0.318
18.7%
26.5%
Mushrooms common (UK)
0.72
42.4%
60.0%
India (Goyal 2006)

Champignon fresh A.
bisporus (Fin)
Common mushroom (Jap)
0.32
18.8%
26.7%
100
0.42
24.7%
35.0%
85.1
0.39
22.9%
32.5%
125
12.5%
12.5%
417
Mushroom Common
Agaricus bisporus (Aust)
0.342
20.1%
28.5%
110
11.0%
11.0%
310
11.1%
Mushroom, white, raw (Can)
0.318
18.7%
26.5%
86
318
11.4%
Mushroom Portabella raw

Agaricus bisporus (USDA)
0.286
16.8%
23.8%
108
10.8%
10.8%
364
13.0%
0.286
16.8%
23.8%
108
10.8%
10.8%
364
13.0%
0.5
29.4%
41.7%
120
12.0%
12.0%
448
11.8%
16.0%
0.5
29.4%
41.7%
120
12.0%
12.0%
448
11.8%
16.0%
0.286
16.8%
23.8%
108
10.8%
10.8%
364
Nutrient
Mushroom Agaricus bisporus

(Den)
SFK (Ger)
Mushroom Portabella
Mushroom Brown Italian or
Crimini raw Agaricus
bisporus (USDA)
(Crimini) raw (Can)
Mushroom Portabella
exposed to UV light raw A.
bisporus (USDA)
364
13.0%
359
12.8%
86
318
11.4%
80
320
11.4%
N/A
N/A
N/A
N/A
98
364
13.0%
350
12.5%
363
13.0%
10.1%
10.0%
257
10.1%
10.0%
11.0%
14.9%
13.0%
Summary Table for RAW COMMON MUSHROOMS (Agaricus bisporus) providing >10% RDI/AI of key minerals /100g
Selenium
(mcg)
Males
19
years
and
over
Females
19 years
and
over
Zinc
(mg)
Males
19
years
and
over
Females
19 years
and over
Iron
(mg)
Males
19
years
and
over
Females
19-50
years
Females
over 50
years
RDI
70
60
RDI
14
RDI
18
Agariscus bisporus white

(Matilla 2002)
11
15.7%
18.3%
N/A
N/A
Agariscus bisporus brown

(Matilla 2002)
25
35.7%
41.7%
N/A
N/A
Mushrooms white Agaricus

bisporus (USDA)
9.3
13.3%
15.5%
0.52
0.5
Mushrooms common (UK)
12.9%
15.0%
0.4
0.6
N/A
N/A
0.5
0.4
0.4
0.3
10.8%
0.48
0.31
Nutrient
India (Goyal 2006)
N/A
Champignon fresh A. bisporus

(Fin)
11
Common mushroom (Jap)
N/A

(Den)
SFK (Ger)
15.7%
6.47
18.3%
7.02
10.0%
11.7%
0.54
1.19
Mushroom Common Agaricus

bisporus (Aust)
15.4
22.0%
25.7%
0.56
0.27
Mushroom, white, raw (Can)
9.3
13.3%
15.5%
0.52
0.5
Mushroom Portabella raw

18.6
26.6%
31.0%
0.53
0.31
18.6
26.6%
31.0%
0.53
0.31
26
37.1%
43.3%
1.1
13.8%
0.4
26
37.1%
43.3%
1.1
13.8%
0.4
18.6
26.6%
31.0%
0.53
Mushroom Portabella
Mushroom Brown Italian or
Crimini raw Agaricus bisporus
(USDA)
(Crimini) raw (Can)
Mushroom Portabella exposed
to UV light raw A. bisporus
(USDA)
0.31
258
14.9%
14.9%
Table2 Average %RDI/AI content for each Key MINERAL /100g

Mineral
Average %
Comments
Copper
M 21.7%
F 30.8%
1.7mg male 19 and over

1.2mg female 19 and over
Phosphorous
M and F 11.1%

1000mg Female 19 and over
Potassium
M 11.5%
F 13%
3800 mg male 19 and over

Selenium
M 22.5%
F 25.2%
70mcg male 19 and over

60mcg female 19 and over
# >10% RDI provided by 13 of 16 mushrooms for M and F
Male 19 and over 10% 37.1%
Female 19 and over 10.8%-43.3%

Mushroom Brown Italian or Crimini raw Agaricus bisporus
(UDSA) and (Can) providing the greatest amount
Zinc
F 13.8% only

8mg females 19 and over
Iron
M and F (over 50)

14.9% only

18mg females 19-50 and over
8mg females over 50
# >10% RDI provided by 2 of 16 Mushrooms for Females 19

years :
(UDSA) and (Can)
# >10% RDI provided by 1 of 16 mushrooms
Mushroom Agaricus bisporus SFK (Ger) at 14.9 %
Range male 19 and over 12.9- 42.4%
Range female 19 and over 18.3 -60%

Mushrooms , common (UK) Providing the greatest amount
Range male and female 19 and over 10-12.5%

Mushroom Agaricus Bisporus SFK (Ger) providing the
greatest amount
# >10% AI provided by M 3 and F 15 of 16 Mushrooms
Range female 19 and over 11.1-16%

(UDSA) and (Can) at 11.8% providing the greatest amount
259
Summary Table for RAW CULINARY SPECIALTY MUSHROOMS providing >10% AI for protein and fibre /100g
Protein
(g)
Males
19-70
years
Males
over
70
years
Females
19-70
years
Females
over 70
years
Fibre
(g)
Males
19
years
and
over
Females
19 years
and
over
Energy
(kcal/kj)
RDI
64
81
46
57
AI
30
25
RDI
3.5
11.7%
14.0%
18/75
Shiitake dong gwoo (Fin)
1.8
3.3
11.0%
13.2%
27/111
Shiitake (Log grown)
1.5
0.6
Mushroom shiitake raw

Lentinus edodes (USDA)
2.24
2.5
Shimej Bunashimeji (Jap)
2.7
3.7
Oyster, Eringii, raw (Jap)
3.6
Oyster, Usuhiratake, raw (Jap)
6.1
Oyster (Jap)
3.3
2.6
Oyster (USDA)
3.31
2.3
33/138
2.4
26/110
3.2
Mushroom Boletus, Russula

(Fin)
1.8
1.9
Chantarelle (Fin)
1.8
False Morel (Fin)
1.8
1.9
18/75
2.1
1.5
21/89
Oyster Pleurotus spp SFKGer
2.35
5.85
Nutrient
Shiitake Nama-shiitake (Jap)
Oyster Pleurotte (Fin)
13.3%
10.7%
260
N/A
10.0%
34/142
12.3%
14.8%
18/75
4.3
14.3%
17.2%
24/100
3.8
12.7%
15.2%
23/96
10.4%
20/84
20.0%
24.0%
41/172
28/116
20.0%
19.5%
24.0%
23.4%
17/73
10/45
Summary Table for RAW CULINARY SPECIALTY MUSHROOMS providing >10% AI for protein and fibre /100g
continued
Protein
(g)
Males
19-70
years
Males
over
70
years
Females
19-70
years
Females
over 70
years
Fibre
(g)
Males
19
years
and
over
Females
19 years
and
over
RDI
64
81
46
57
AI
30
25
Nutrient
Mushroom Oyster, raw (Can)
3.31
2.3
Enoki (USDA)
2.66
2.7
10.8%
Mushroom Enoki, raw (Can)
2.56
2.7
10.8%
Winter Mushrooms (Jap)
2.7
3.9
13.0%
15.6%
Nameko, raw (Jap)
1.7
3.3
11.0%
13.2%
Maitake, raw (Jap)
3.7
2.7
2.4
10.0%
12.0%
2.1
3.3
11.0%
13.2%
2.3
2.5
3.6
3.3
11.0%
13.2%
Shimeji Hatakeshimeji, raw

(Jap)
3.1
3.5
11.7%
14.0%
3.7
4.1
13.7%
16.4%
4.7
15.7%
18.8%
Maitake (USDA)
1.94
2.7
1.49
3.8
Morel, raw (USDA)
3.12
2.8
11.2%
Maitake, raw (Can)
1.94
2.7
10.8%
25
25
10.8%
10.0%
10.8%
12.7%
15.2%
100g of fresh culinary specialty mushrooms provide an average of 12.3 % of the AI for fibre for both male and females aged 19 years and over whereas the common variety mushroom
provides an average of 5.5%
AI for fibre males 19yeas and over equals 30g and for females 19 years and over equals 25g
261
Summary Table for RAW CULINARY SPECIALTY MUSHROOMS providing >10% RDI/AI of key vitamins /100g
Nutrient
Thiamin
(B1)
(mg)
Males
19
years
and
over
Females
19 years
and
over
Riboflavin
(B2) (mg)
Males
19-70
years
Males
over
70
years
Females
19-70
years
Females
over 70
years
Niacin
equivalents
(B3) (mg)
Males
19
years
and
over
Females
19 years
and
over
Folate
(mcg)
Males
19
years
and
over
Females
19 years
and
over
RDI
1.2
1.1
RDI
1.3
1.6
1.1
1.3
RDI
16
14
RDI
400
400
11.9%
17.3%
14.6%
3.8
23.8%
27.1%
42
10.5%
10.5%
13.6%
11.5%
2.6
16.3%
18.6%
25
Shiitake Nama-shiitake
(Jap)
0.1
0.19
14.6%
0.05
0.15
11.5%
0.4
0.4
30.8%
25.0%
36.4%
30.8%
4.5
28.1%
32.1%
N/A
0.217
16.7%
13.6%
19.7%
16.7%
3.887
24.3%
27.8%
13

Shimej Bunashimeji
(Jap)
33.3%
36.4%
0.015
0.16
13.3%
14.5%
0.16
12.3%
10.0%
14.5%
12.3%
6.6
41.3%
47.1%
28
0.14
11.7%
12.7%
0.28
21.5%
17.5%
25.5%
21.5%
8.1
50.6%
57.9%
80
20.0%
20.0%
Oyster, Usuhiratake, raw

(Jap)
0.3
25.0%
27.3%
0.41
31.5%
25.6%
37.3%
31.5%
6.9
43.1%
49.3%
100
25.0%
25.0%
Oyster (Jap)
0.4
33.3%
36.4%
0.4
30.8%
25.0%
36.4%
30.8%
10.7
66.9%
76.4%
92
23.0%
23.0%
Oyster (USDA)
0.125
10.4%
11.4%
0.349
26.8%
21.8%
31.7%
26.8%
4.956
31.0%
35.4%
38
0.07
0.2
15.4%
12.5%
18.2%
15.4%
5.2
32.5%
37.1%
51
12.8%
12.8%
0.03
0.37
28.5%
23.1%
33.6%
28.5%
8.4
52.5%
60.0%
35
Mushroom Boletus,
Russula (Fin)
0.1
0.4
30.8%
25.0%
36.4%
30.8%
5.9
36.9%
42.1%
25.5
Chantarelle (Fin)
0.1
0.4
30.8%
25.0%
36.4%
30.8%
5.9
36.9%
42.1%
21
False Morel (Fin)
0.1
0.4
30.8%
25.0%
36.4%
30.8%
5.9
36.9%
42.1%
21
0.1
0.42
32.3%
26.3%
38.2%
32.3%
6.1
38.1%
43.6%
35
0.285
21.9%
17.8%
25.9%
21.9%
0.1
Oyster Pleurotus spp

SFK-Ger
0.191
15.9%
17.4%
262
N/A
continued
Nutrient
Thiamin
(B1)
(mg)
Males
19
years
and
over
Females
19 years
and
over
Riboflavin
(B2) (mg)
Males
19-70
years
Males
over
70
years
Females
19-70
years
Females
over 70
years
Niacin
equivalents
(B3) (mg)
Males
19
years
and
over
Females
19 years
and
over
Folate
(mcg)
Males
19
years
and
over
Females
19 years
and
over
1.3
1.6
1.1
1.3
RDI
16
14
RDI
400
400
RDI
1.2
1.1
RDI
Mushroom Oyster, raw

(Can)
0.125
10.4%
11.4%
0.349
Enoki (USDA)
0.225
18.8%
20.5%
0.2
15.4%
12.5%
18.2%
15.4%
7.032
44.0%
50.2%
48
12.0%
12.0%
Mushroom Enoki, raw

(Can)
0.179
14.9%
16.3%
0.162
12.5%
10.1%
14.7%
12.5%
6.372
39.8%
45.5%
52
13.0%
13.0%
0.24
20.0%
21.8%
0.17
13.1%
10.6%
15.5%
13.1%
6.8
42.5%
48.6%
75
18.8%
18.8%
Nameko, raw (Jap)
0.07
5.1
31.9%
36.4%
58
14.5%
14.5%
Maitake, raw (Jap)
0.25
20.8%
22.7%
0.49
37.7%
30.6%
44.5%
37.7%
9.1
56.9%
65.0%
60
15.0%
15.0%
0.27
22.5%
24.5%
0.34
26.2%
21.3%
30.9%
26.2%
6.1
38.1%
43.6%
33
0.5
38.5%
31.3%
45.5%
38.5%
56.3%
64.3%
38
20.0%
20.0%
Yanagimatsutake, raw
(Jap)
Shimeji Honshimeji, raw
(Jap)
Numeisugitake, raw
(Jap)
Shimeji Hatakeshimeji,
raw (Jap)
Kuroawabitake, raw
(Jap)
5.456
0.12
0.08
10.9%
27
0.16
13.3%
14.5%
0.34
26.2%
21.3%
30.9%
26.2%
5.9
36.9%
42.1%
19
0.17
14.2%
15.5%
0.33
25.4%
20.6%
30.0%
25.4%
12
75.0%
85.7%
80
0.12
10.0%
10.9%
0.49
37.7%
30.6%
44.5%
37.7%
6.1
38.1%
43.6%
25
0.21
17.5%
19.1%
0.22
16.9%
13.8%
20.0%
16.9%
2.9
18.1%
20.7%
65
16.3%
16.3%
50.0%
57.1%
63
15.8%
15.8%
0.1
Maitake (USDA)
0.146
0.1
12.2%
0.242
18.6%
15.1%
22.0%
18.6%
6.585
41.2%
47.0%
21
0.015
0.215
16.5%
13.4%
19.5%
16.5%
4.085
25.5%
29.2%
Morel, raw (USDA)
0.069
0.205
15.8%
12.8%
18.6%
15.8%
2.252
14.1%
16.1%
Maitake, raw (Can)
0.146
0.242
18.6%
15.1%
22.0%
18.6%
6.941
43.4%
49.6%
29
12.2%
13.3%
13.3%
263
Nutrient
Vit B6
(mg)
Males
19-50
years
Males
over
50
years
Females
19-50
years
Females
over 50
years
Pantothenic
acid (mg)
Males
19 years
and over
Females
19 years
and
over
RDI
1.3
1.7
1.3
1.5
AI
18.0%
27.0%
1.5
25.0%
37.5%
0.86
14.3%
21.5%
Shiitake Nama-shiitake (Jap)
0.11
1.08
N/A
N/A
N/A
N/A

0.293
0.08
0.18
13.8%
10.6%
13.8%
12.0%
1.61
26.8%
40.3%
0.23
17.7%
13.5%
17.7%
15.3%
2.44
40.7%
61.0%
Oyster (Jap)
0.1
2.4
40.0%
60.0%
Oyster (USDA)
0.11
1.294
21.6%
32.4%
N/A
N/A
0.18
13.8%
10.6%
13.8%
12.0%
N/A
Mushroom Boletus, Russula

(Fin)
0.22
16.9%
12.9%
16.9%
14.7%
N/A
Chantarelle (Fin)
0.04
False Morel (Fin)
0.22
16.9%
12.9%
16.9%
14.7%
N/A
0.18
13.8%
10.6%
13.8%
12.0%
N/A
Oyster Pleurotus spp SFK-Ger
0.88
67.7%
51.8%
67.7%
58.7%
N/A
22.5%
17.2%
22.5%
19.5%
N/A
264
continued
Nutrient
Vit B6
(mg)
Males
19-50
years
Males
over
50
years
Females
19-50
years
Females
over 50
years
Pantothenic
acid (mg)
Males
19 years
and over
Females
19 years
and
over
RDI
1.3
1.7
1.3
1.5
AI
Mushroom Oyster, raw (Can)
0.11
1.294
21.6%
32.4%
Enoki (USDA)
0.1
1.35
22.5%
33.8%
Mushroom Enoki, raw (Can)
0.081
1.067
17.8%
26.7%
0.12
1.4
23.3%
35.0%
Nameko, raw (Jap)
0.05
1.25
20.8%
31.3%
Maitake, raw (Jap)
0.07
0.79
13.2%
19.8%
0.11
2.61
43.5%
65.3%
0.13
1.97
32.8%
49.3%
0.08
1.77
29.5%
44.3%
0.12
1.32
22.0%
33.0%
Shimeji Hatakeshimeji, raw

(Jap)
0.12
2.48
41.3%
62.0%
0.09
1.32
22.0%
33.0%
0.15
1.91
31.8%
47.8%
Maitake (USDA)
0.056
0.27
0.044
1.075
17.9%
26.9%
Morel, raw (USDA)
0.136
Maitake, raw (Can)
0.056
10.0%
11.5%
10.5%
10.0%
11.5%
10.0%
10.5%
0.44
0.27
265
11.0%
Vit C
(mg)
Males
19
years
and
over
Females
19 years
and
over
Vit D
(mcg)
Males
19-50
years
Males
51-70
years
Males
over
70
years
Females
19-50
years
Females
51-70
years
Females
over 70
years
RDI
45
45
AI
10
15
10
15
(Jap)
10
22.2%
22.2%
40.0%
20.0%
13.3%
40.0%
20.0%
13.3%
2.1
0.1
N/A
N/A
N/A
0.4
2
40.0%
20.0%
13.3%
40.0%
20.0%
13.3%
Nutrient

Shimej Bunashimeji
(Jap)
15.6%
15.6%
40.0%
20.0%
13.3%
40.0%
20.0%
13.3%

(Jap)
120.0%
60.0%
40.0%
120.0%
60.0%
40.0%
Oyster (Jap)
10
20.0%
10.0%
20.0%
10.0%
Oyster (USDA)
0.7
14.0%
1.6
<0.1mcg
2.5
2.9
58.0%
29.0%
19.3%
58.0%
29.0%
19.3%
Mushroom Boletus,
Russula (Fin)
11.1%
11.1%
4.4
88.0%
44.0%
29.3%
88.0%
44.0%
29.3%
Chantarelle (Fin)
11.1%
11.1%
12.8
256.0%
128.0%
85.3%
256.0%
128.0%
85.3%
False Morel (Fin)
11.1%
11.1%
4.4
88.0%
44.0%
29.3%
88.0%
44.0%
29.3%
110.0%
55.0%
36.7%
110.0%
55.0%
36.7%
22.2%
22.2%
1.3
5.5

SFK-Ger
0.6
N/A
14.0%
266
continued
Vit C
(mg)
Males
19
years
and
over
Females
19 years
and
over
Vit D
(mcg)
Males
19-50
years
Males
51-70
years
Males
over 70
years
Females
19-50
years
Females
51-70
years
Females
over 70
years
RDI
45
45
AI
10
15
10
15
18.0%
Nutrient

(Can)
0.9
Enoki (USDA)
0.1
Mushroom Enoki, raw

(Can)
0.1
Nameko, raw (Jap)
Tr mg
Tr mcg
Maitake, raw (Jap)
18.0%
20.0%
10.0%
20.0%
10.0%
60.0%
30.0%
60.0%
30.0%
Tr mg
20.0%
10.0%
20.0%
10.0%
Tr mg
80.0%
40.0%
80.0%
40.0%
20.0%
10.0%
20.0%
10.0%
raw (Jap)
20.0%
10.0%
20.0%
10.0%
20.0%
10.0%
20.0%
10.0%
Tr mg
20.0%
10.0%
20.0%
10.0%
80.0%
40.0%
26.7%
80.0%
40.0%
26.7%
Maitake (USDA)
28.1
562.0%
281.0%
187.3%
562.0%
281.0%
187.3%
N/A
5.3
106.0%
53.0%
35.3%
106.0%
53.0%
35.3%
Morel, raw (USDA)
N/A
5.1
102.0%
51.0%
34.0%
102.0%
51.0%
34.0%
Maitake, raw (Can)
29.5
590.0%
295.0%
196.7%
590.0%
295.0%
196.7%
(Jap)
(Jap)
267
20.0%
26.7%
20.0%
26.7%
Table 3 Average %RDI/AI content for each Key Vitamin /100g

Vitamin
Average %
Thiamine (B1)
M 17.4%
F 18.9%
1.2mg male 19 years and over

1.1mg Female 19 years and over
Riboflavin (B2)
M 21.5%
F 25.4%
1.3mg male 19-70 : 1.6mg men>70

1.1mg Female 19-70: 1.3mg female>70
Niacin
M 39.1%
F 44.6%

Folate
M and 16.7%
Vitamin B6
M 18.7%
F 19.2%
1.3mg male 19-50: 1.7mg men>50

1.3mg Female 19-50: 1.5mg female>50
M 26%
F 37.8%

Vitamin C
M and F 15.6%
Vitamin D
M and F 73.1%
5mcg Male and female 19-50

10mcg male and female 51-70
Pantothenic
acid
Comments
# >10% RDI provided by 19 of the 33 mushrooms for M and F
Range male 19 and over 10 33.3%

Shiitake (Log grown) and Oyster (Jap) providing the greatest amount
# >10% RDI provided by M 30 and F 31 of 33 mushrooms
Range female 19 and over 10.9- 45.5%

Shimeiji Hatakeshimeiji raw (Jap) providing the greatest amount
Range male 19 and over 14.1-75%

Tamogitake, raw (Jap) providing the greatest amount
Range male and female 19 and over 10.5-25%


Shimeiji Hatakeshimeiji raw (Jap) providing the greatest amount
# >10% AI provided by M 21 and F 22 of 33 mushrooms
Range male 19 and over 13.243.5%
Range female 19 and over 11 65.3%

Yanagimatsutake, Raw (Jap) providing the greatest amount
Range male and females 19 and over 11.1-22.2%

Shiitake Nama-shiitake (Jap) and Oyster (Jap) providing the greatest amount
Range male and female 70 and over: 13.3-197%

Maitake, Raw (Can) being the greatest contributor providing 29.5mcg per 100g
268
Summary Table for RAW CULINARY SPECIALTY MUSHROOMS providing >10% RDI/AI of key minerals /100g
Copper
(mg)
Males
19
years
and
over
Females
19 years
and
over
Phosphorus
(mg)
Males
19
years
and
over
Females
19 years
and
over
Manganese
(mg)
Males
19
years
and
over
Females
19 years
and
over
Potassium
(mg)
Males
19
years
and
over
Females
19 years
and
over
AI
1.7
1.2
RDI
1000
1000
AI
5.5
AI
3800
2800
Nutrient
(Jap)
0.05
73
0.23
280
N/A
73
N/A
224
N/A
39
N/A
N/A

Shimej Bunashimeji
(Jap)
0.142
11.8%
0.06
112
11.2%
11.2%
0.23
304
100
10.0%
10.0%
0.12
380
10.0%
13.6%
12.1%
16.4%
0.15
12.5%
120
12.0%
12.0%
0.07
460

(Jap)
0.15
12.5%
110
11.0%
11.0%
0.11
220
Oyster (Jap)
0.15
12.5%
100
10.0%
10.0%
0.16
340
Oyster (USDA)
0.244
20.3%
120
12.0%
12.0%
0.113
420
11.0%
11.0%
N/A
298
14.4%
10.0%
10.9%
12.1%
11.1%
15.0%
N/A
110
N/A
47
N/A
270
Mushroom Boletus,
Russula (Fin)
N/A
72
N/A
340
12.1%
Chantarelle (Fin)
N/A
72
N/A
340
12.1%
False Morel (Fin)
N/A
72
N/A
340
12.1%
N/A
55
N/A
290
10.4%

SFK-Ger
0.12
67
0.13
N/A
10.0%
269
10.6%
continued
Copper
(mg)
Males
19
years
and
over
Females
19 years
and
over
Phosphorus
(mg)
Males
19
years
and
over
Females
19 years
and
over
Manganese
(mg)
Males
19
years
and
over
Females
19 years
and
over
Potassium
(mg)
Males
19
years
and
over
Females
19 years
and
over
AI
1.7
1.2
RDI
1000
1000
AI
5.5
AI
3800
2800

(Can)
0.244
14.4%
20.3%
120
12.0%
12.0%
0.113
420
11.1%
15.0%
Enoki (USDA)
0.107
105
10.5%
10.5%
0.075
359
12.8%
Mushroom Enoki, raw

(Can)
0.091
109
10.9%
10.9%
0.079
368
13.1%
0.1
110
11.0%
11.0%
0.07
340
12.1%
Nameko, raw (Jap)
0.11
66
0.06
230
Maitake, raw (Jap)
0.27
15.9%
22.5%
130
13.0%
13.0%
0.05
330
11.8%
11.0%
11.0%
0.08
360
12.9%
10.7%
Nutrient
(Jap)
(Jap)
Numeisugitake, raw
(Jap)
0.2
11.8%
16.7%
110
0.36
21.2%
30.0%
75
0.1
300
0.19
11.2%
15.8%
65
0.05
260
0.32
18.8%
26.7%
85
0.06
190
0.14
11.7%
70
0.17
280
10.0%
0.15
12.5%
100
0.07
300
10.7%
raw (Jap)
Kuroawabitake, raw
(Jap)
10.0%
10.0%
0.24
14.1%
20.0%
40
0.12
410
Maitake (USDA)
0.252
14.8%
21.0%
74
0.059
204
0.353
20.8%
29.4%
57
0.286
Morel, raw (USDA)
0.625
36.8%
52.1%
194
Maitake, raw (Can)
0.252
14.8%
21.0%
74
19.4%
19.4%
0.587
0.059
270
10.7%
11.7%
10.8%
14.6%
506
13.3%
18.1%
411
10.8%
14.7%
204
Selenium
(mcg)
Males
19
years
and
over
Females
19 years
and
over
Zinc
(mg)
Males
19
years
and
over
Females
19 years
and
over
Iron
(mg)
Males
19
years
and
over
Females
19-50
years
Females
over 50
years
RDI
70
60
RDI
14
RDI
18
Nutrient
(Jap)
N/A
0.4
0.3
0.8
N/A
N/A

5.7
1.03
N/A
0.5
0.4
N/A
0.7
0.3

(Jap)
N/A
0.9
11.3%
0.6
Oyster (Jap)
N/A
12.5%
0.7
Oyster (USDA)
2.6
0.77
1.33
1.2
0.7
0.4
11
15.7%
18.3%
0.9
Mushroom Boletus,
Russula (Fin)
14.1
20.1%
23.5%
0.6
Chantarelle (Fin)
18
25.7%
30.0%
0.8
False Morel (Fin)
39
55.7%
65.0%

Oyster Pleurotus spp SFKGer
0.3
10.0%
0.3
0.7
12.9%
0.41
16.6%
16.6%
0.8
10.0%
10.0%
2.7
33.8%
15.0%
33.8%
2.7
33.8%
15.0%
33.8%
0.7
2.7
33.8%
15.0%
33.8%
1.2
0.6
12.5%
12.5%
N/A
0.73
1.23
15.4%
15.4%
11.3%
10.0%
271
continued
Selenium
(mcg)
Males
19
years
and
over
Females
19 years
and
over
Zinc
(mg)
Males
19
years
and
over
Females
19 years
and
over
Iron
(mg)
Males
19
years
and
over
Females
19-50
years
Females
over 50
years
RDI
70
60
RDI
14
RDI
18
Nutrient

(Can)
2.6
0.77
1.33
16.6%
16.6%
Enoki (USDA)
2.2
0.65
1.15
14.4%
14.4%
Mushroom Enoki, raw

(Can)
2.2
0.61
1.09
13.6%
13.6%
N/A
0.6
1.1
13.8%
13.8%
Nameko, raw (Jap)
N/A
0.5
0.7
Maitake, raw (Jap)
N/A
0.8
N/A
0.6
N/A
0.8
13.8%
13.8%
N/A
0.4
0.6
N/A
0.6
0.8
10.0%
10.0%
raw (Jap)
N/A
0.4
0.6
N/A
0.7
0.5
N/A
0.8
16.3%
16.3%
Maitake (USDA)
2.2
0.75
0.3
2.2
0.71
3.47
43.4%
19.3%
43.4%
Morel, raw (USDA)
2.2
2.03
12.18
152.3%
67.7%
152.3%
Maitake, raw (Can)
2.2
0.75
(Jap)
(Jap)
10.0%
0.5
0.5
10.0%
10.0%
14.5%
25.4%
1.1
1.3
0.3
272
Table 4 Average %RDI/AI content for each key mineral /100g

Mineral
Average %
Copper
M 17.4%
F 20%

1.2mg Female 19 and over
Phosphorous
M and F 11.7%
Manganese
M 10.7 % Only
F 11.7% Only

Potassium
M 11.3%
F 12.7%

Selenium
M 29.3%
F 34.2%

Zinc
M 14.5%
F 12.3%
14mg males 19 years and over

8mg Females 19 years and over
Iron
M 28.1%
F 27.7%

18mg females 19-50: 8mg female over 50
Comments

Morel, raw (USDA) providing the greatest amount

Morel, Raw (USDA) Providing the greatest amount
Male 19 and over 10.7% and 11.7% female Morel,

Raw (USDA) Providing the greatest amount
Range female 19 years and over 10-18.1%

Chanterelle, Raw (USDA) providing the greatest amount.
#>10% RDI provided by 4 of 33 mushrooms for M and F
Range female 19 years and over 18.3-65%

False Morel (Fin) providing the greatest amount
Males 19 and over only one at 14.5%
Range females 19 and over 10-25.4%

Morel ,Raw (USDA) provided >10% at 14.5%.
# >10% RDI provided by M F 16 of 33 mushrooms
Male 19 and over and females over 50 Range 10152.3%

Morel, Raw (USDA) providing the greatest at 12.2mg/100g
273
Summary Tables for COOKED COMMON MUSHROOMS (Agaricus bisporus) providing >10% RDI/AI of key vitamins
/100g
Nutrient
Mushrooms, canned, drained

solids (USDA)
Thiamin
(B1)
(mg)
Males
19
years
and
over
Females
19 years
and
over
Riboflavin
(B2) (mg)
Males
19-70
years
Males
over 70
years
Females
19-70
years
Females
over 70
years
Niacin
equivalents
(B3) (mg)
Males
19
years
and
over
Females
19 years
and
over
Folate
(mcg)
Males
19
years
and
over
Females
19 years
and
over
RDI
1.2
1.1
RDI
1.3
1.6
1.1
1.3
RDI
16
14
RDI
400
400
1.593
10.0%
11.4%
12
0.085
0.021
0.06
0.431
33.2%
26.9%
39.2%
33.2%
5.35
33.4%
38.2%
16
0.06
0.431
33.2%
26.9%
39.2%
33.2%
5.35
33.4%
38.2%
16
0.096
0.463
35.6%
28.9%
42.1%
35.6%
3.987
24.9%
28.5%
20
Mushrooms, cooked, boiled,

drained, without salt (USDA)
0.073
0.3
23.1%
18.8%
27.3%
23.1%
4.46
27.9%
31.9%
18

drained, with salt (USDA)
0.073
0.3
23.1%
18.8%
27.3%
23.1%
4.46
27.9%
31.9%
18
Mushrooms, common Fried

in Butter (UK)
0.09
0.34
26.2%
21.3%
30.9%
26.2%
2.3
14.4%
16.4%
11
Mushrooms, common, fried

in corn oil (UK)
0.09
0.34
26.2%
21.3%
30.9%
26.2%
2.3
14.4%
16.4%
11
Common Mushroom Boiled

(Jap)
0.05
0.28
21.5%
17.5%
25.5%
21.5%
2.7
16.9%
19.3%
19
Common mushroom, canned

in brine solids (Jap)
0.03
0.24
18.5%
15.0%
21.8%
18.5%
Matsutake, canned in brine

solids (Jap)
0.04
0.3
23.1%
18.8%
27.3%
23.1%
12.5%
14.3%
Mushroom, canned Agaricus

bisphorus (Den)
0.081
0.402
30.9%
25.1%
36.5%
30.9%
4.07
25.4%
29.1%
23
Mushrooms canned (Ger)
0.02
0.19
14.6%
11.9%
17.3%
14.6%
1.22
0.042
0.661
50.8%
41.3%
60.1%
50.8%
7.02
Mushrooms, white
microwaved (USDA)
Mushrooms, white
microwaved (Can)
Mushrooms, white, stir fried
(USDA)
Mushroom, common, stirfried (no oil) Agariscus

bisphorus (Aust)
Mushroom, golden, Asian,
canned in brine, drained
(Aust)
0.23
19.2%
20.9%
0.05
1.55
274
N/A
43.9%
50.1%
27
11.1%
N/A
/100g
continued
Thiamin
(B1)
(mg)
Males
19
years
and
over
Females
19 years
and
over
Riboflavin
(B2) (mg)
Males
19-70
years
Males
over 70
years
Females
19-70
years
Females
over 70
years
Niacin
equivalents
(B3) (mg)
Males
19
years
and
over
Females
19 years
and
over
Folate
(mcg)
Males
19
years
and
over
Females
19 years
and
over
RDI
1.2
1.1
RDI
1.3
1.6
1.1
1.3
RDI
16
14
RDI
400
400
0.14
10.8%
12.7%
10.8%
1.37
Champignon, fried Agaricus

bisphorus (Fin)
0.08
0.43
33.1%
26.9%
39.1%
33.1%
6.1
38.1%
43.6%
29.3
Mushroom fried Agaricus

bisporus (Fin)
0.12
0.49
37.7%
30.6%
44.5%
37.7%
7.2
45.0%
51.4%
18
0.03
0.46
35.4%
28.8%
41.8%
35.4%
10.3
64.4%
73.6%
53.8
13.5%
13.5%
Champignon, canned
Agarisuc bisphorus (Fin)
0.02
0.25
19.2%
15.6%
22.7%
19.2%
5.9
36.9%
42.1%
12
Mushroom in vinegar (Fin)
0.1
0.38
29.2%
23.8%
34.5%
29.2%
5.1
31.9%
36.4%
18.9
Mushroom, boiled, drained

(Can)
0.073
0.3
23.1%
18.8%
27.3%
23.1%
4.86
30.4%
34.7%
18

with salt (Can)
0.073
0.3
23.1%
18.8%
27.3%
23.1%
4.86
30.4%
34.7%
18
Mushroom, straw, canned,

drained solids (Can)
0.013
0.07
Mushroom, white, stir-fried

(Can)
0.096
0.463
Mushroom Canned, drained

solids (Can)
0.085
0.021
Mushroom Portabella grilled

0.072
0.403
31.0%
25.2%
36.6%
Mushroom Portabella
(Portabello), grilled (Can)
0.072
0.403
31.0%
25.2%
Mushroom Portabella
exposed to UV light grilled A
bisporus (USDA)
0.072
0.403
31.0%
25.2%

drained solids (USDA)
0.013
0.07
Nutrient
Mushroom, straw, Asian,

(Aust)
10.0%
10.9%
N/A
0.926
35.6%
28.9%
42.1%
35.6%
4.604
28.8%
32.9%
20
1.943
12.1%
13.9%
12
31.0%
6.255
39.1%
44.7%
19
36.6%
31.0%
6.255
39.1%
44.7%
19
36.6%
31.0%
6.255
39.1%
44.7%
19
0.224
275
20
38
/100g
Vit B6
(mg)
Males
19-50
years
Males
over 50
years
Females
19-50
years
Females
over 50
years
Pantothenic
acid (mg)
Males
19
years
and
over
Females
19 years
and
over
Biotin
(mcg)
Males
19
years
and
over
Females
19 years
and
over
RDI
1.3
1.7
1.3
1.5
AI
AI
30
25
0.061
0.811
13.5%
20.3%
N/A
0.049
1.96
32.7%
49.0%
N/A
0.049
1.96
32.7%
49.0%
N/A
0.042
1.45
24.2%
36.3%
N/A

0.095
2.16
36.0%
54.0%
N/A

0.095
2.16
36.0%
54.0%
N/A
Mushrooms, common Fried in

Butter (UK)
0.19
1.4
23.3%
35.0%
26.7%
32.0%
Mushrooms, common, fried in

corn oil (UK)
1.4
23.3%
35.0%
26.7%
32.0%
Common Mushroom Boiled (Jap)
0.08
1.43
23.8%
35.8%
N/A
Common mushroom, canned in

brine solids (Jap)
0.01
0.11
N/A

solids (Jap)
0.01
0.05
N/A

bisphorus (Den)
0.06
16.7%
25.0%
16
53.3%
64.0%
0.06
0.8
13.3%
20.0%
N/A
Mushroom, common, stir-fried

(no oil) Agariscus bisphorus
(Aust)
0.04
2.17
36.2%
54.3%
16.7
55.7%
66.8%

canned in brine, drained (Aust)
N/A
N/A
Nutrient

solids (USDA)
Mushrooms, white microwaved
(USDA)
(Can)
(USDA)
14.6%
11.2%
14.6%
12.7%
276
N/A
Summary Tables for COOKED COMMON MUSHROOMS (Agaricus bisporus) providing >10% RDI/AI of key
vitamins/100g
continued
Vit B6
(mg)
Males
19-50
years
Males
over 50
years
Females
19-50
years
Females
over 50
years
Pantothenic
acid (mg)
Males
19
years
and
over
Females
19 years
and
over
Biotin
(mcg)
Males
19
years
and
over
Females
19 years
and
over
RDI
1.3
1.7
1.3
1.5
AI
AI
30
25
Nutrient
Mushroom, straw, Asian, canned

in brine, drained (Aust)
N/A

bisphorus (Fin)
0.21

bisporus (Fin)
0.05
0.28
Champignon, canned Agarisuc

bisphorus (Fin)
N/A
N/A
N/A
N/A
N/A
N/A
N/A
N/A
0.07
N/A
N/A
0.07
N/A
N/A
Mushroom, boiled, drained (Can)
0.095
2.16
36.0%
54.0%
N/A
Mushroom, boiled, drained with

salt (Can)
0.095
2.16
36.0%
54.0%
N/A

0.014
0.412
10.3%
N/A
Mushroom, white, stir-fried (Can)
0.042
1.45
24.2%
36.3%
N/A

solids (Can)
0.061
0.811
21.0%
20.3%
N/A

0.122
1.262
21.0%
31.6%
N/A
Mushroom Portabella
0.122
1.262
21.0%
31.6%
N/A
Mushroom Portabella exposed to

UV light grilled A bisporus
(USDA)
0.122
1.262
21.0%
31.6%
N/A

0.014
0.412
10.3%
N/A
16.2%
21.5%
12.4%
16.5%
16.2%
21.5%
14.0%
18.7%
277
Summary Tables for COOKED COMMON MUSHROOMS (Agaricus bisporus) providing >10% RDI/AI of key
vitamins/100g
Vit C
(mg)
Males
19
years
and
over
Females
19 years
and
over
Vit A
(Retinol
Equivalents)
(mcg)
Males
19
years
and
over
Females
19 years
and
over
Vit D
(mcg)
Males
19-50
years
Males
51-70
years
Males
over 70
years
Females
19-50
years
Females
51-70
years
Females
over 70
years
RDI
45
45
RDI
900
700
AI
10
15
10
15
20.0%
10.0%
Nutrient

solids (USDA)
0.2
0.3
0.3
0.2

0.2

0.2

Butter (UK)
85
Mushrooms, common, fried in

corn oil (UK)
tr

(Jap)
20.0%
10.0%

brine solids (Jap)
40.0%
20.0%
13.3%
40.0%
20.0%
13.3%
Tr mg
120.0%
60.0%
40.0%
120.0%
60.0%
40.0%

bisphorus (Den)
2.1
10
1.7
N/A
N/A
Mushroom, common, stir-fried

(no oil) Agariscus bisphorus
(Aust)
23
N/A

59
N/A

(USDA)
(Can)
(USDA)

solids (Jap)
12.1%
278
0.1
/100g
continued
Vit C
(mg)
Males
19
years
and
over
Females
19 years
and
over
Vit A
(Retinol
Equivalents)
(mcg)
Males
19
years
and
over
Females
19 years
and
over
Vit D
(mcg)
Males
19-50
years
Males
51-70
years
Males
over 70
years
Females
19-50
years
Females
51-70
years
Females
over 70
years
RDI
45
45
RDI
900
700
AI
10
15
10
15
Nutrient

53
N/A

bisphorus (Fin)
0.9
N/A
0.5
10.0%

bisporus (Fin)
6.1
N/A
15.8
316.0%
158.0%
105.3%
316.0%
158.0%
105.3%
2.5
N/A
4.5
90.0%
45.0%
30.0%
90.0%
45.0%
30.0%
N/A
0.2
1.9
N/A
4.8
96.0%
48.0%
32.0%
96.0%
48.0%
32.0%

(Can)
0.5
10.0%
Mushroom, boiled, drained with

salt (Can)
0.2

N/A

(Can)
0.2

solids (Can)
1.5
0.2

0.3
Mushroom Portabella
0.3
Mushroom Portabella exposed

to UV light grilled A bisporus
(USDA)
N/A
14.1
141.0%
94.0%

N/A

bisphorus (Fin)
13.6%
13.6%
279
282.0%
10.0%
10.0%
141.0%
94.0%
282.0%
Table 5 Average %RDI/AI content for each key vitamin /100g

Vitamin
Thiamine (B1)
Average %
Comments
M 14.6%
F 15.9%
M 25.7%
F 30.5%

Niacin (B3)
M 30%
F 33.4%

Folate
M & F 13.5%
Vitamin B6
M 15.4%
F 16.3%
1.3mg males 19-50: 1.7mg males 50 and over

1.3mg females19-50; 1.5mg females 50 and over
Pantothenic
acid
M 25.9%
F 35.6%

Biotin
M 40.6%
F 48.7%

Vitamin C

Mushroom, Fried Agaricus Bisporus (Fin)
Vitamin A
M and F 13.6 %
only
F 12.1% only
Vitamin D
M and F 80.9%


Mushroom,common Fried in butter (UK)
Range male and female 70 and over: 17-105.3%

Maitake, fried Agaricus Bisporus (Fin) being the greatest contributor providing
15.8mcg per 100g
Riboflavin (B2)
# >10% RDI provided by 2 of the 30 mushrooms for M and F

Mushroom, Golden, Asian, canned in brine, drained (Aust) providing the greatest
amount

Mushroom, common, stir-fried (no OIL) agaricus bisporus (Aust) providing the
greatest amount
Range male 19 and over 1064.4%
Range female 19 and over 11.1 73.6%

Boletus edible, boiled (Fin) providing thte greatest amount
Boletus edible, boiled (Fin) providing thte greatest amount
1.3mg male 19-70: 1.6mg men>70

280
Range female 19 and over 12.7 -21.5%

Boletus edible, boiled (fin) providing the greatest amount
# >10% AI provided by M 19 and F 21 of the 30 mushrooms
Range female 19 and over 10.3 54.3%

greatest amount
# >10% AI provided by 4 of the 30 mushrooms for M and F
Range female 19 and over 32 66.8%

greatest amount
Summary Tables for COOKED COMMON MUSHROOMS (Agaricus bisporus) providing >10% RDI/AI of key minerals
/100g
Copper
(mg)
Males
19
years
and
over
Females
19 years
and
over
Phosphorus
(mg)
Males
19
years
and
over
Females
19 years
and
over
Sodium
(mg)
Males
19
years
and
over
Females
19 years
and
over
Potassium
(mg)
Males
19
years
and
over
Females
19 years
and
over
Selenium
(mcg)
Males
19
years
and
over
Females
19 years
and
over
AI
1.7
1.2
RDI
1000
1000
AI
460
460
AI
3800
2800
RDI
70
60
0.235
13.8%
19.6%
66
425
92.4%
92.4%
129
0.37
21.8%
30.8%
127
12.7%
12.7%
17
488
12.8%
17.4%
18
25.7%
30.0%
0.37
21.8%
30.8%
127
12.7%
12.7%
17
488
12.8%
17.4%
18
25.7%
30.0%
0.291
17.1%
24.3%
105
10.5%
10.5%
12
396
10.4%
14.1%
13.9
19.9%
23.2%
0.504
29.6%
42.0%
87
356
12.7%
11.9
17.0%
19.8%
0.504
29.6%
42.0%
87
238
51.7%
51.7%
356
12.7%
13.4
19.1%
22.3%
Mushrooms, common
Fried in Butter (UK)
0.4
23.5%
33.3%
110
11.0%
11.0%
150
32.6%
32.6%
340
12.1%
12
17.1%
20.0%
Mushrooms, common, fried

in corn oil (UK)
0.4
23.5%
33.3%
100
10.0%
10.0%
340
12.1%
12
17.1%
20.0%
0.36
21.2%
30.0%
99
310
11.1%
N/A
0.19
11.2%
15.8%
55
350
76.1%
76.1%
85
N/A

solids (Jap)
0.31
18.2%
25.8%
36
130
28.3%
28.3%
N/A
Mushroom, canned
Agaricus bisphorus (Den)
0.48
28.2%
40.0%
76
190
3.3
0.48
28.2%
40.0%
69
319
121
8.6
12.3%
14.3%
0.645
37.9%
53.8%
208
29.1
41.6%
48.5%
Nutrient
Mushrooms, canned,
Mushrooms, white
microwaved (USDA)
Mushrooms, white
microwaved (Can)
Mushrooms, white, stir
fried (USDA)
Mushrooms, cooked,
boiled, drained, without salt
(USDA)
Mushrooms, cooked,
boiled, drained, with salt
(USDA)

(Jap)
Common mushroom,
canned in brine solids
(Jap)
Mushroom, common, stirfried (no oil) Agariscus

bisphorus (Aust)
(Aust)
0.06
20.8%
20.8%
49
69.3%
15
300
281
69.3%
585
65.2%
65.2%
24
4.1
15.4%
20.9%
N/A
/100g
continued
Copper
(mg)
Males
19
years
and
over
Females
19 years
and
over
Phosphorus
(mg)
Males
19
years
and
over
Females
19 years
and
over
Sodium
(mg)
Males
19
years
and
over
Females
19 years
and
over
Potassium
(mg)
Males
19
years
and
over
Females
19 years
and
over
Selenium
(mcg)
Males
19
years
and
over
Females
19 years
and
over
AI
1.7
1.2
RDI
1000
1000
AI
460
460
AI
3800
2800
RDI
70
60
240
52.2%
52.2%
25
Nutrient

(Aust)
0.04
48
Champignon, fried
Agaricus bisphorus (Fin)
N/A
119.1

bisporus (Fin)
N/A
90
257.2
N/A
72.3
9.2
Champignon, canned
Agarisuc bisphorus (Fin)
N/A
76
520
113.0%
113.0%
190
N/A
68.4
983
213.7%
213.7%
323
11.5%

(Can)
0.504
29.6%
42.0%
87
356

with salt (Can)
0.504
29.6%
42.0%
87
238
51.7%
51.7%
356

0.133
11.1%
61
384
83.5%
83.5%
78

(Can)
0.291
17.1%
24.3%
105
Mushroom Canned,
0.235
13.8%
19.6%
66
Mushroom Portabella
grilled Agaricus bisporus
(USDA)
0.389
22.9%
32.4%
135
13.5%
13.5%
11
437
11.5%
15.6%
Mushroom Portabella
0.389
22.9%
32.4%
135
13.5%
13.5%
11
437
11.5%
Mushroom Portabella
exposed to UV light grilled
A bisporus (USDA)
0.389
22.9%
32.4%
135
13.5%
13.5%
11
437
11.5%

0.133
11.1%
61
11.9%
10.5%
11.9%
10.5%
27.2
55.9%
12
425
384
282
55.9%
436.3
11.5%
15.6%
13.1
18.7%
21.8%
417.3
11.0%
14.9%
22
31.4%
36.7%
415.4
10.9%
14.8%
16.9
24.1%
28.2%
32.4
46.3%
54.0%
12.7%
11.9
17.0%
19.8%
12.7%
13.4
19.1%
22.3%
15.2
21.7%
25.3%
13.9
19.9%
23.2%
21.9
31.3%
36.5%
15.6%
21.9
31.3%
36.5%
15.6%
21.9
31.3%
36.5%
15.2
21.7%
25.3%
396
92.4%
83.5%
92.4%
83.5%
N/A
2.9
10.4%
14.1%
129
78
4.1
/100g
Zinc
(mg)
Males
19
years
and
over
Females
19 years
and
over
Iron
(mg)
Males
19
years
and
over
Females
19-50
years
Females
over 50
years
Iodine
(mcg)
Males
19
years
and
over
Females
19 years
and
over
RDI
14
RDI
18
RDI
150
150
Nutrient
Mushrooms, canned, drained solids

(USDA)
0.72
0.79
N/A
0.73
0.33
N/A
0.73
0.33
N/A
Mushrooms, white, stir fried (USDA)
0.57
0.25
N/A

0.87
10.9%
1.74
21.8%
21.8%
N/A

0.87
10.9%
1.74
21.8%
21.8%
N/A

Butter (UK)
0.5
12.5%
12.5%
11
Mushrooms, common, fried in corn

oil (UK)
0.5
12.5%
12.5%
Common Mushroom Boiled (Jap)
0.6
0.3

(USDA)
(Can)

brine solids (Jap)
Matsutake, canned in brine solids

(Jap)
0.7

bisphorus (Den)
0.93
N/A
Mushroom, common, stir-fried (no

oil) Agariscus bisphorus (Aust)
1.06
Mushroom, golden, Asian, canned

in brine, drained (Aust)
0.4
12.5%
11.6%
13.3%
N/A
0.8
10.0%
10.0%
N/A
3.3
41.3%
41.3%
N/A
0.84
10.5%
10.5%
0.5
0.8
10.0%
10.0%
N/A
18.3%
0.5
1
0
12.5%
283
12.5%
/100g
continued
Zinc
(mg)
Males
19
years
and
over
Females
19 years
and
over
Iron
(mg)
Males
19
years
and
over
Females
19-50
years
Females
over 50
years
Iodine
(mcg)
Males
19
years
and
over
Females
19 years
and
over
RDI
14
RDI
18
RDI
150
150
12.5%
12.5%
15.3%
15.3%
Nutrient
Mushroom, straw, Asian, canned in

brine, drained (Aust)
0.3

bisphorus (Fin)
0.6
0.5
Mushroom fried Agaricus bisporus

(Fin)
0.9
1.4

bisphorus (Fin)
0.5
0.9
Mushroom, boiled, drained (Can)
1.3
41.3%
14.8
15.0%
15.0%
1.5
0.8
10.0%
10.0%
23
11.3%
2.6
32.5%
32.5%
0.87
10.9%
1.74
21.8%
21.8%
N/A
Mushroom, boiled, drained with salt

(Can)
0.87
10.9%
1.74
21.8%
21.8%
N/A
Mushroom, straw, canned, drained

solids (Can)
0.67
1.43
17.9%
17.9%
N/A
Mushroom, white, stir-fried (Can)
0.57
0.25
N/A
Mushroom Canned, drained solids

(Can)
0.72
0.79
N/A

0.65
0.4
N/A
Mushroom Portabella (Portabello),

grilled (Can)
0.65
0.4
N/A
Mushroom Portabella exposed to

UV light grilled A bisporus (USDA)
0.65
0.4
N/A
Mushroom, straw, canned, drained

solids (USDA)
0.67
1.43
10.0%
11.3%
3.3
41.3%
17.5%
1.2
17.9%
284
18.3%
14.4%
17.9%
N/A

Mineral
Average %
Copper
M 23.1%
F 30.8%

Phosphorous
M and F 12.8%
Sodium
M and F 77.4%
460 mg male and female 19 and over
Potassium
M 11.8%
F 14.4%

Selenium
M 24.3%
F 28.3%

Zinc
M 10% only
F 12.1%

Iron
M 19.1%
F 18.8%

18mg females 19-50 years
Iodine
M and F 15.3%
only
Comments
# >10% AI provided by M 21, F23 of 30 mushrooms
Range male 19 and over 11.2- 37.9%

Mushroom Common; stir fried (NO oil) agaricus bisporus (Aust).
Provide the greatest amount

# >10% AI provided by 15 of 30 mushrooms
Range male and female 19 and over 28.3-213.7%
Mushroom in Vinegar (Fin) Provide the greatest amount
# >10% AI provided by M 11 and F19 of 30 mushrooms
Range female 19 years and over 11.1-20.9%


Mushroom in Vinegar (Fin) Provide the greatest amount
# >10%RDI provided by M 1 and F 10 of 30 mushrooms
Range 10.9-17.5% - Females only

Boletus edible, boiled (Fin) providing the greatest amount
Range male 19 and over; 10 41.3%
Range female 19 -50; 14.4-18.3%
Range over 50 years and over 10 41.3%

Mushroom Fried agaricus bisporus (Fin) and Matsutake, canned in
brine solids (Jap) Provided the greatest amounts
Only 1 mushroom from 30 provided >10 RDI this being
champignion, canned agaricus bisporus (Fin)
285
Summary Table for COOKED CULINARY SPECIALTY MUSHROOMS providing >10% RDI/AI for fibre /100g
Fibre
(g)
Males
19
years
and
over
Females
19 years
and
over
AI
30
25
Mushrooms Shiitake, Stir fried

3.6
12.0%
14.4%
Mushrooms, shiitake, cooked

without salt (USDA)
2.1
Mushrooms, shiitake, cooked with

salt (USDA)
2.1
Shiitake Hoshi-shiitake boiled (Jap)
7.5
25.0%
30.0%
Shiitake Nama-shiitake, boiled (Jap)
4.7
15.7%
18.8%
5.2
17.3%
20.8%
6.4
21.3%
25.6%
16.3
54.3%
65.2%
12.0%
14.4%
Nutrient
Tree ears, Shiro-kikurage, boiled

(Jap)
Tree ears, Arage-kikurage, boiled
(Jap)
26
Mushroom, shiitake, cooked (Can)
2.1
Mushroom, shiitake,stir-fried (Can)
3.6
Nameko boiled (Jap)
2.7
10.8%
Nameko canned in brine (Jap)
2.5
10.0%
Maitake, boiled (Jap)
3.6
12.0%
14.4%
Oyster mushrooms boiled (Jap)
3.7
12.3%
14.8%
Winter mushroom bottled in

seasoning (Jap)
4.1
13.7%
16.4%
Winter Mushroom boiled (Jap)
4.5
15.0%
18.0%
Shimeji Bunashimeji boiled (Jap)
4.8
16.0%
19.2%
100g of cooked culinary specialty mushrooms provide an average of 13.5 % of the AI26 for fibre for both male and females aged 19 years and
over whereas the common variety mushroom provides an average of 8.5%
286
Summary Table for COOKED CULINARY SPECIALTY MUSHROOMS providing >10% RDI/AI of key vitamins /100g
Nutrient
Thiamin
(B1)
(mg)
Males
19
years
and
over
Females
19 years
and
over
Riboflavin
(B2) (mg)
Males
19-70
years
Males
over 70
years
Females
19-70
years
Females
over 70
years
Niacin
equivalents
(B3) (mg)
Males
19
years
and
over
Females
19 years
and
over
Folate
(mcg)
Males
19
years
and
over
Females
19 years
and
over
RDI
1.2
1.1
RDI
1.3
1.6
1.1
1.3
RDI
16
14
RDI
400
400
24.2%
27.6%
14
11.0%
11.0%
15.8%
15.8%
17.8%
17.8%

0.099
0.274
21.1%
17.1%
24.9%
21.1%
3.87

without salt (USDA)
0.037
0.17
13.1%
10.6%
15.5%
13.1%
1.5
10.7%
21

with salt (USDA)
0.037
0.17
13.1%
10.6%
15.5%
13.1%
1.5
10.7%
21
0.06
0.23
17.7%
14.4%
20.9%
17.7%
12.5%
14.3%
44
0.1
0.18
13.8%
11.3%
16.4%
13.8%
3.1
19.4%
22.1%
24
0.01
0.06
Tr mg
0.05
Tr mg
0.07
0.1
0.037
0.17
13.1%
10.6%
15.5%
13.1%
1.567
0.099
0.274
21.1%
17.1%
24.9%
21.1%
4.053
Nameko boiled (Jap)
0.06
0.11
0.03
0.07
0.12
10.0%
10.9%
0.19
14.6%
11.9%
17.3%
Oyster mushrooms boiled

(Jap)
0.3
25.0%
27.3%
0.27
20.8%
16.9%

seasoning (Jap)
3.6
300.0%
327.3%
0.17
13.1%
10.6%
0.19
15.8%
17.3%
0.13
10.0%
Shimeji Bunashimeji boiled

(Jap)
0.15
12.5%
13.6%
0.12
Shiitake Hoshi-shiitake boiled

(Jap)
Shiitake Nama-shiitake, boiled
(Jap)
Tree ears, Kiurage, boiled
(Jap)
Tree ears, Shiro-kikurage,
boiled (Jap)
Tree ears, Arage-kikurage,
boiled (Jap)
Mushroom, shiitake, cooked
(Can)
Mushroom, shiitake,stir-fried
(Can)
11.2%
21
25.3%
29.0%
14
4.7
29.4%
33.6%
63
2.1
13.1%
15.0%
13
14.6%
3.3
20.6%
23.6%
28
24.5%
20.8%
43.8%
50.0%
71
15.5%
13.1%
4.4
27.5%
31.4%
39
11.8%
10.0%
3.7
23.1%
26.4%
30
5.2
32.5%
37.1%
25
10.0%
10.9%
287
Summary Table for COOKED CULINARY SPECIALTY MUSHROOMS providing >10% RDI/AI of key vitamins /100g
Vit B6
(mg)
Males
19-50
years
Males
over 50
years
Females
19-50
years
Females
over 50
years
Pantothenic
acid (mg)
Males
19
years
and
over
Females
19 years
and
over
Vit D
(mcg)
Males
19-50
years
Males
51-70
years
Males
over 70
years
Females
19-50
years
Females
51-70
years
Females
over 70
years
RDI
1.3
1.7
1.3
1.5
AI
AI
10
15
10
15

0.174
13.4%
10.2%
13.4%
11.6%
1.36
22.7%
34.0%
0.5
10.0%
10.0%

without salt (USDA)
0.159
12.2%
12.2%
10.6%
3.594
59.9%
89.9%
0.7
14.0%
14.0%

with salt (USDA)
0.159
12.2%
12.2%
10.6%
3.594
59.9%
89.9%
0.7
14.0%
14.0%
0.1
1.05
17.5%
26.3%
40.0%
20.0%
13.3%
40.0%
20.0%
13.3%
0.09
1.18
19.7%
29.5%
40.0%
20.0%
13.3%
40.0%
20.0%
13.3%
0.01
39
780.0%
390.0%
260.0%
780.0%
390.0%
260.0%
0.01
93
1860.0%
930.0%
620.0%
1860.0%
930.0%
620.0%
0.01
15
300.0%
150.0%
100.0%
300.0%
150.0%
100.0%
Nutrient

(Jap)
(Jap)
(Jap)
boiled (Jap)
(Can)
(Can)
0.159
12.2%
0.174
13.4%
10.2%
12.2%
10.6%
3.594
59.9%
89.9%
0.7
14.0%
14.0%
13.4%
11.6%
1.36
22.7%
34.0%
0.5
10.0%
10.0%
20.7%
31.0%
20.0%
10.0%
20.0%
10.0%
13.0%
20.0%
10.0%
20.0%
10.0%
Nameko boiled (Jap)
0.04
1.24
0.02
0.52
0.04
0.9
15.0%
22.5%
80.0%
40.0%
26.7%
80.0%
40.0%
26.7%
0.06
2.36
39.3%
59.0%
40.0%
20.0%
13.3%
40.0%
20.0%
13.3%

seasoning (Jap)
0.09
1.04
17.3%
26.0%
20.0%
10.0%
20.0%
10.0%
0.09
0.96
16.0%
24.0%
20.0%
10.0%
20.0%
10.0%
0.06
1.25
20.8%
31.3%
60.0%
30.0%
60.0%
30.0%
288
20.0%
20.0%
Table 7 Average %RDI/AI content for each key vitamin /100g

Vitamin
Average %
Thiamine (B1)
M 72.7%
F 79.3%

Riboflavin (B2)
M 14.4%
F 16.5%
1.3mg male 19-70: 1.6mg men>70

Niacin (B3)
M 24.7%
F 24.5%

Folate
M and F 14.8%
400mcg male and female 19 yars and over
Vitamin B6
M 12%
F 11.8%

1.3mg females19-50: 1.5mg females 50 and over
Pantothenic
acid
M 30.1%
F 42.9%

Vitamin D
M and F
163.5%

289
Comments
Range male 19 and over 10 300%

Winter Mushroom bottled in seasoning (Jap) providing 3.6mg/ 100g.
# >10 % RDI provided by M 11 and F 13 of 17 mushrooms

Mushroom Shiitake, stir-fried (Can) providing the greatest amount
# >10%RDI provided by M 11 and F 14 of 17 mushrooms

Oyster Mushroom, boilded (Jap) Providing the greatest amount
Range male and female 19 and over 11 -17.8%

Oyster Mushroom, boilded (Jap) Providing the greatest amount

Mushrooms Shiitake, stir fried lentinus Adodes (USDA) and mushrrom
Shiitake, stir-fried (Can).
# >10% AI provided by M 13 and F 14 of 17 mushrooms
Range male 19 and over 1559.9%

Mushroom, shiitake cooked (Can) Provided the greatet amount
## >10% RDI provided by all 17 of 17 mushrooms for M and F * aged
19-50 years
Range male and female 51-70: 10 930%
Range male and female 70 and over: 13.3-620%

Tree Ears, Shiro-Kikurage, boilded (Jap) being the greatest contributor
providing93 mcg per 100g
Summary Table for COOKED CULINARY SPECIALTY MUSHROOMS providing >10% RDI/AI of key minerals /100g
Copper
(mg)
Males
19
years
and
over
Females
19 years
and
over
Phosphorus
(mg)
Males
19
years
and
over
Females
19 years
and
over
Manganese
(mg)
Males
19
years
and
over
Females
19 years
and
over
Sodium
(mg)
Males
19
years
and
over
Females
19 years
and over
AI
1.7
1.2
RDI
1000
1000
AI
5.5
AI
460
460
13.6%
111
11.1%
11.1%
0.223
52.2%
52.2%
369.6%
369.6%
Nutrient

0.163

without salt (USDA)
0.896
52.7%
74.7%
29
0.204

with salt (USDA)
0.896
52.7%
74.7%
29
0.204
240
0.09
43
0.11
0.07
67
0.24
29
0.204
0.03
10
0.53
0.01
11
0.12
0.04
11
0.2
10
0.223

(Jap)
(Jap)
(Can)
Tree ears, Shiro-kikurage,
boiled (Jap)
boiled (Jap)
(Can)
0.896
52.7%
74.7%
13.6%
111
Nameko boiled (Jap)
0.12
10.0%
56
0.05
0.04
39
0.08
0.17
89
0.04
0.11
86
0.15

seasoning (Jap)
0.08
150
15.0%
15.0%
0.24
1700
0.06
110
11.0%
11.0%
0.05
Shimeji Bunashimeji boiled

(Jap)
0.06
110
11.0%
11.0%
0.13
14.2%
11.1%
0.163
10.0%
11.1%
10.6%
290
Summary Table for COOKED CULINARY SPECIALTY MUSHROOMS providing >10% RDI/AI of key minerals /100g
continued
Potassium
(mg)
Males
19
years
and
over
Females
19 years
and
over
Selenium
(mcg)
Males
19
years
and
over
Females
19 years
and
over
Zinc
(mg)
Males
19
years
and
over
Females
19 years
and
over
Iron
(mg)
Males
19
years
and
over
Females
19-50
years
Females
over 50
years
AI
3800
2800
RDI
70
60
RDI
14
RDI
18
11.6%
6.3
10.5%
0.96
12.0%
0.53
Nutrient

326

without salt (USDA)
117
24.8
35.4%
41.3%
1.33
16.6%
0.44

with salt (USDA)
117
24.8
35.4%
41.3%
1.33
16.6%
0.44

(Jap)
(Jap)
(Can)
(Jap)
Tree ears, Arage-kikurage, boiled
(Jap)
(Can)
220
0.4
0.3
250
0.5
0.3
117
24.8
35.4%
41.3%
1.33
16.6%
0.44
37
0.2
0.7
79
0.3
0.2
0.1
1.7
326
11.6%
6.3
10.5%
0.96
12.0%
210
0.4
0.6
100
0.5
0.8
160
0.7
0.4
260
1.4

seasoning (Jap)
320
270
340
11.4%
12.1%
291
17.5%
21.3%
10.0%
10.0%
0.53
Nameko boiled (Jap)
10.0%
21.3%
0.7
0.6
0.8
10.0%
10.0%
0.6
12.5%
12.5%
0.5
0.5
Table 8 Average %RDI/AI content for each Key MINERAL /100g

Mineral
Average %
Copper
M 42%
F 39.3%

Phosphorous
M and F 11.8%
Manganese
F 10.6% only
Sodium
M and F 210%
Potassium
F 11.7% only

Selenium
M 3%
F 5%

Zinc
M 10% only
F 15.2%
14mg Male 19 and over

Iron
M 13.4%
F 10.8%

Comments
# >10% RDI provided by M 4 and F 7 of the 17 mushrooms

Mushroom common Shiitake, cooked without Salt (USDA) and
Cooked with Salt (USDA) and Mushroom common shiitake,
cooked (Can)
# >10% RDI provided by 5 of 17 mushrooms M and F
Range male and female 19 and over 11-15%
Winter mushroom Bottled in seasoning providing the greatest
amount.
# >10% AI provided by 1of 17 mushrooms F only
by Tree Ears, kiurage, boiled (Jap) providing the greatest amount
#>10% AI for 2 of 17 mushrooms for M and F
Winter mushrrom bottled in seasoning providing the greatest
amount (Likely seasoning not mushroom)
# >10% AI provided for females 19 and over only. With only 4 of
the 17 mushrooms contributing to >10%.
Range female 19 years and over 11.4-12.1%
Shimeji bunashimeji, boiled (Jap) Provided the greatest amount
Male 19 and over 35.4%
Female 19 and over range 10.5 -41.3%
Mushroom common Shiitake, cooked without Salt (USDA) and
Cooked with Salt (USDA) and Mushroom common shiitake,
cooked (Can)
Oyster mushroom, boiled (Jap) providing the greatest amount
Range for male 19 and over and female over 50, 10-21.3%
Tree Ears, Arage-kikurage, boiled (Jap)
292
Summary Table for DRIED CULINARY SPECIALTY MUSHROOMS providing >10% RDI/AI for fibre /20g weight
Fibre
(g)
Males
19
years
and
over
Females
19 years
and
over
AI
30
25
27.3%
32.8%
27.3%
32.7%
46.7%
56.1%
Nutrient
27
Mushrooms, shiitake, dried

2.30
Shiitake Hoshi-shiitake dried

(Jap)
8.20
Mushroom, shiitake, dried

(Can)
2.30
1.10
Maitake dried (Jap)
8.18
Mushroom Milk Caps, salted

(Fin)
0.58
Fungi, Cloud ears, dried

(Can)
14.02
20g of dried culinary specialty mushrooms provide an average of 25.7 % of the AI27 for fibre for both male and females aged 19 years and
over.
293
Summary Table for DRIED CULINARY SPECIALTY MUSHROOMS providing >10% RDI/AI of key vitamins /20g weight
Nutrient
Thiamin
(B1)
(mg)
Males
19
years
and
over
Females
19 years
and
over
Riboflavin
(B2) (mg)
Males
19-70
years
Males
over 70
years
Females
19-70
years
Females
over 70
years
Niacin
equivalents
(B3) (mg)
Males
19
years
and
over
Females
19 years
and
over
Folate
(mcg)
Males
19
years
and
over
Females
19 years
and
over
RDI
1.2
1.1
RDI
1.3
1.6
1.1
1.3
RDI
16
14
RDI
400
400
12.0%
12.0%
11.0%
11.0%
Mushrooms, shiitake,
dried Lentinus edodes
(USDA)
0.06
0.25
19.5%
15.9%
23.1%
19.5%
2.82
17.6%
20.1%
33
Shiitake Hoshi-shiitake
dried (Jap)
0.10
0.28
21.5%
17.5%
25.5%
21.5%
3.36
21.0%
24.0%
48
Mushroom, shiitake,
dried (Can)
0.06
0.25
19.5%
15.9%
23.1%
19.5%
2.92
18.3%
20.9%
33
Shiitake, dried (Log

grown)
0.20
16.7%
18.2%
0.20
15.4%
12.5%
18.2%
15.4%
2.00
12.5%
14.3%
N/A
Maitake dried (Jap)
0.25
20.7%
22.5%
0.38
29.5%
24.0%
34.9%
29.5%
12.82
80.1%
91.6%
44
Mushroom Milk Caps,

salted (Fin)
0.02
0.08

(Can)
0.0
0.17
1.14
13.0%
10.6%
294
15.3%
13.0%
1.59
4.2
10.0%
11.4%
7.6
Summary Table for DRIED CULINARY SPECIALTY MUSHROOMS providing >10% RDI/AI of key vitamins /20g weight
continued
Vit B6
(mg)
Males
19-50
years
Males
over 50
years
Females
19-50
years
Females
over 50
years
Pantothenic
acid (mg)
Males
19
years
and
over
Females
19 years
and
over
Vit D
(mcg)
Males
19-50
years
Males
51-70
years
Males
over 70
years
Females
19-50
years
Females
51-70
years
Females
over 70
years
RDI
1.3
1.7
1.3
1.5
AI
AI
10
15
10
15

Lentinus edodes
(USDA)+A10
0.19
14.8%
11.4%
14.8%
12.9%
4.38
72.9%
109.4%
0.78
15.6%
dried (Jap)
0.09
1.59
26.4%
39.7%
3.40
68.0%
34.0%
22.7%

(Can)
0.19
4.38
72.9%
109.4%
0.78
15.6%
N/A
N/A
Maitake dried (Jap)
0.06
0.73
56.0%
28.0%
18.7%
Mushroom Milk Caps,

salted (Fin)
0.04
21.2%
10.6%

(Can)
0.02
Nutrient
14.8%
11.4%
14.8%
12.9%
15.6%
34.0%
68.0%
15.6%
N/A
2.80
56.0%
28.0%
N/A
1.06
21.2%
10.6%
0.10
295
22.7%
12.2%
18.4%
18.7%
Table 9 Average %RDI/AI content for each Key Vitamin /20g

Vitamin
Average %
Thiamine (B1)
M18.7%
F 20.4%

Riboflavin (B2)
M 17.9%
F 21.5%
1.3mg male 19-70: 1.6mg men>70

Niacin (B3)
M 26.6 %
F 30.4%

Folate
M and F 11.5%
400mcg male and female19 and over
Vitamin B6
M 13.1%
F 13.9%

1.3mg females19-50: 1.5mg females 50 and over
Pantothenic
acid
M 46.1%
F 69.2%

Vitamin D
M and F 29%

296
Comments
Range female 19 and over 18.2- 22.5%

Maitake dried (Jap) providing the greatest amount
# >10% RDI provided by all 6 of the 7 listed mushrooms for M and F
Range male 19 and over 10.6 -29.5%

Maitake dried (Jap) Proving the greatest amount
# >10%RDI provided by all 6 of the 7 listed mushrooms for M and F
Range male 19 and over 10 - 80.1%
Range female 19 and over 11.4 - 91.6%

Maitake dried (Jap) Proving the greatest amount
# >10%RDI provided by all 2 of 7 mushrooms for M and F
Range male and female 19 and over 11 - 12%

Shiitake Hoshie-Shiitake dried (Jap) Proving the greatest amount
# >10%RDI provided by all 2 of the 7 mushrooms for M and F

Maitake dried (Can) and Mushrooms, Shiitake, dried Lentinus edodes (USDA)
Proving the greatest amount

Maitake dried (Can) and Mushrooms, Shiitake, dried Lentinus edodes (USDA)
Proving the greatest amount
Range male and female 19 50: 15.668%
Range male and female 51-70: 10.6-34%
Range male and female 70 and over: 18.7 -22.7%

Shiitake Hoshi-shiitake, dried (Fin) being the greatest contributor providing
3.4mcg per 100g
Summary Table for DRIED CULINARY SPECIALTY MUSHROOMS providing >10% RDI/AI of key minerals /20g weight
Copper
(mg)
Males
19
years
and
over
Females
19 years
and
over
Phosphorus
(mg)
Males
19
years
and
over
Females
19 years
and
over
Sodium
(mg)
Males
19
years
and
over
Females
19 years
and over
Potassium
(mg)
Males
19
years
and
over
Females
19 years
and
over
AI
1.7
1.2
RDI
1000
1000
AI
460
460
AI
3800
2800
Mushrooms, shiitake,
dried Lentinus edodes
(USDA)
1.03
60.8%
86.1%
58.8
2.6
306.8
dried (Jap)
0.10
62
1.2
420
Mushroom, shiitake,
dried (Can)
1.03
58.8
2.6
306.8
11.0%
Shiitake, dried (Log

grown)
N/A
48
2.6
306.8
11.0%
Maitake dried (Jap)
0.36
0.6
500
Mushroom Milk Caps,

salted (Fin)
N/A
14.4
196.6

(Can)
0.04
36.8
7.0
Nutrient
60.8%
20.9%
86.1%
29.7%
140
14.0%
14.0%
297
42.7%
42.7%
68
150.8
11.0%
11.1%
13.2%
15.0%
17.9%
Summary Table for DRIED CULINARY SPECIALTY MUSHROOMS providing >10% RDI/AI of key minerals /20g weight
Selenium
(mcg)
Males
19
years
and
over
Females
19 years
and
over
Zinc
(mg)
Males
19
years
and
over
Females
19 years
and
over
Iron
(mg)
Males
19
years
and
over
Females
19-50
years
Females
over 50
years
RDI
70
60
RDI
14
RDI
18

9.22
13.2%
15.4%
1.53
10.9%
19.2%
0.34
dried (Jap)
N/A

(Can)
9.22
N/A
N/A
Maitake dried (Jap)
N/A
1.38
Mushroom Milk Caps,

salted (Fin)
7.2
10.3%
12.0%
0.14
0.54

(Can)
8.68
12.4%
14.5%
0.26
1.18
Nutrient
0.46
13.2%
15.4%
1.53
0.34
10.9%
19.2%
0.34
0.78
17.3%
298
0.52
14.7%
14.7%

Mineral
Average %
Copper
M 47.5%
F 67.3%

Phosphorous
M and F 14%
Only
Sodium
M and F 42.7%
only
Potassium
M 12.1%
F 13.1%

Selenium
M 4.3%
F 14.3%

Zinc
M 10.9% only
F 18.5%

Iron
M and F 14.7%

18 female 19-50 : 8mg females 51 and over
Comments
Range female 19 and over 29.7 - 86.1%

Shiitake Dried Lentinus edodes (USDA) and Mushroom,
shiitake, dried (Can) providing the greatest amount
# >10% RDI provided by 1of 7 mushrooms for M and F
Male and female 19 and over 14%

Maitake dried (Jap) providing the greatest amount
Male and female 19 and over 42.7%

Mushroom, milk caps, salted (Fin) providing the greatest
amount. Nil other provided >10% AI for sodium
# >10 % AI provided by 2 of 7 mushrooms for M and F
Range male 19 years and over 11.1-13.2%
Range female 19 years and over 11-17.9%

Maitake dried (Jap) Providing the greatest amount.
# >10 % RDI provided by 3 of 7mushrooms
Range female 19 and over 12 -15.4%

Shiitake Dried Lentinus edodes (USDA) and Mushroom,
shiitake, dried (Can) providing the greatest amount
providing the greatest amount
#>10% RDI provided by M 2 and F 3 of 7 mushrooms
Male 19 and over 10.9%

Mushrooms, Shiitake dried Lentinus edode (USDA)
Mushrooms, Shiitake dried (Can) providing the greatest
amount
# >10 % RDI provided by 1 of 7 mushrooms for M and F
# 14.7 % RDI provided by
Fungi cloud ears dried (Can) containing 1.18mg/20g
299
mushrooms (Pleurotus ostreatus), Shiitake mushrooms (Lentinus edodes), and Maitake (Grifola
frondosa) mushrooms (Xu et al., 2012b). The use of mushrooms as anti-cancer therapeutics
has also recently been reviewed (Patel and Goyal, 2012, Petrova, 2012, Soumya et al., 2011),
as have the levels of evidence from human trials of mushroom intake (Roupas et al., 2012).
5.1.1.1 Breast Cancer

A recent clinical trial with Korean women has evaluated the association between mushroom
intake and the risk of breast cancer according to hormone receptor status. Mushroom intake
and breast cancer risk were examined among 358 breast cancer patients and 360 cancer-free
controls. Intake of mushrooms was assessed using a quantitative food frequency questionnaire.
Greater mushroom intake was related to lower risk of breast cancers among premenopausal
women with the association being stronger for premenopausal women with estrogen receptor
(ER)+/progesterone receptor (PR)+ tumours than those with ER/PR tumours. The results
suggest that high consumption of mushrooms may be related to a lower risk for breast cancer
among premenopausal women, and the association may be more robust among women with
hormone receptor positive tumours (Aesun et al., 2010).
An epidemiological study of women with histologically confirmed breast cancer has identified
that daily intake and the average consumption frequency of mushrooms were inversely
associated with breast cancer risk, and a strong inverse association was found in postmenopausal women, but not in pre-menopausal women (Hong et al., 2008), which is in contrast
to another epidemiological study that has suggested a decreased risk of breast cancer from
mushroom consumption by pre-menopausal women (Shin et al., 2010). In this latter study,
greater mushroom intake was related to lower risk of breast cancers among premenopausal
women for the highest vs. the lowest quartile intake. The association was stronger for
premenopausal women with estrogen receptor (ER)+/progesterone receptor (PR) + tumors than
those with ER-/PR- tumors, suggesting that this effect may be more robust among women with
hormone receptor positive tumors. A possible mechanism for this effect may be via an inhibition
of aromatase activity, described in both in vitro and animal trials (Grube et al., 2001, Chen et al.,
2006), and more recently in a human trial of postmenopausal women diagnosed with breast
cancer (Palomares et al., 2011) for Agaricus bisporus. A subsequent reduction in estrogen,
affecting estrogen receptor positive tumors was reported in animal trials. Recent evidence
suggests that the anti-aromatase compound in Agaricus bisporus is conjugated linoleic acid
(CLA) (Kanaya et al., 2011a).
40
However, an in vitro study using water-based extracts of Coprinellus sp., Coprinus comatus,
Flammulina velutipes, significantly inhibited growth of both estrogen-receptor positive (ER+) and
estrogen-receptor negative (ER-) breast cancer cells, induction of rapid apoptosis on both ER+
and ER- cells, and significantly inhibited MCF-7 tumor colony formation in vitro. These activities
were dose-dependent, regardless of the hormone receptor status of the cancer cells (Gu and
Leonard, 2006).
Higher dietary intake of mushrooms decreased breast cancer risk in both pre- and
postmenopausal women and an additional decreased risk of breast cancer was observed from a
synergistic effect of mushrooms and green tea in a case-controlled study (Zhang et al., 2009).
Vitamin D2 could be one of the protective phytonutrients against breast cancer as mushrooms
are rich in ergosterol, generating vitamin D2 when exposed to ultraviolet B (UVB) light and
ergocalciferol being bioavailable and increasing serum 25(OH) vitamin D2 levels in humans
(Furlanetto, 2009). While these human trials are promising, it should be noted that they were not
direct intervention trials and mushroom consumption was assessed via quantitative food
frequency questionnaires, which can be affected by recall bias.
Studies in animal models and human cell lines have provided insights into the possible
mechanisms involved for the effects of mushrooms and their components on breast cancer, and
several studies have shown that mushroom extracts are able to suppress the proliferation of
breast cancer cell lines, without affecting the proliferation of normal (non-cancer) cell lines
(Israilides et al., 2008, Jedinak and Sliva, 2008). An in vitro study using an aqueous extract of
Agaricus bisporus has identified suppression of aromatase activity and estrogen production as
key mechanisms (Grube et al., 2001), which is supported by an animal model study that has
reported that the major active compounds (in Agaricus bisporus) are unsaturated fatty acids
such as linoleic acid, linolenic acid, and CLA which have been shown to inhibit aromatase
activity (Chen et al., 2006).
Inhibition of proliferation of human breast cancer cell lines has also been suggested to be
mediated via downregulation of Akt/NF-kappaB (transcription factor) signalling in several
mushroom varieties (Jiang et al., 2004a, Jiang et al., 2006, Jin et al., 2008), with a suggestion
that the active components in mushrooms in these effects may be hydroxylated triterpenes
(Jiang et al., 2008). Suppression of the transcription factors NF-kappaB and AP-1 has also been
demonstrated by Ganerderma lucidum (Thyagarajan et al., 2006).
Polysaccharide K (Krestin, PSK), extracted from Coriolus versicolor strain CM-101, is a nonspecific immunomodulatory polysaccharide which induces interleukin 2 (IL-2) and interferon
41
(IFN) , thereby stimulating lymphokine activated killer cells and enhancing natural killer cells
(Sakamoto et al., 2006). Oral administration of PSK has been shown to significantly inhibit
breast cancer growth in tumor-bearing neu transgenic mice (Lu et al., 2011c), with the indication
that PSK is a specific Toll-like receptor 2 (TLR2) agonist and exerts its anti-tumor effects via
stimulation of both innate and adaptive immune pathways. Mushroom polysaccharopeptides
have also been implicated in apoptopic effects in human breast cancer cell lines (Wan et al.,
2008).
A review of the use of mushrooms as adjuvant treatments in breast cancer has reported that
mushroom intake is associated with improvements in the immunological and hematologic
parameters of breast cancer, as well as in the quality of life of breast cancer patients (Novaes et
al., 2011).
5.1.1.2 Colorectal Cancer

A randomized, double-blind, placebo-controlled clinical trial carried out in Brazil over a six
month period with 56 patients has studied life quality of postsurgical patients with colorectal
cancer after supplementation of the diet with Agaricus sylvaticus (30 mg/kg/day). After six
months of treatment, the supplemented group had increased physical activity, improved
disposition and mood, reduced complaints of pain and reduced alterations of sleep such as
insomnia and restless sleep. The supplemented group also presented with increased appetite,
reduced constipation, diarrhea, alternate diarrhea/constipation, flatulence, flatus retention,
pyrosis, postprandial fullness, nausea, abdominal distention and abdominal pain, indicators
which were not observed in the placebo group (Fortes et al., 2010).
A further evaluation of the same patients reported that the Agaricus sylvaticus group had
significantly reduced fasting plasma glucose, total cholesterol, creatinine, aspartate
aminotransferase, alanine aminotransferase, IgA, IgM, systolic blood pressure and diastolic
blood pressure, all effects that were not observed in the placebo group. The data suggest that
dietary supplementation with Agaricus sylvaticus was capable of providing metabolic benefits to
the biochemical, enzymatic and blood pressure parameters of these patients with colorectal
cancer in the postsurgical phase (Fortes and Novaes, 2011).
Polysaccharide krestin (PSK), an extract from Trametes versicolor, has been reported to
reduce toxicity of current treatments used in patients with metastatic colorectal cancer (Shibata
et al., 2011). The effects of PSK in cancer therapy and the possible mechanism of action have
recently been reviewed (Sun et al., 2012).
42
Two meta-analyses of randomised clinical trials have suggested that adjuvant

immunochemotherapy with polysaccharide K from mushrooms can improve the survival of and
disease-free survival of patients with curatively resected colorectal cancer (Oba et al., 2007,
Sakamoto et al., 2006). The reduction of death rate by 29% and of recurrence by 28% by PSK
immunochemotherapy over standard oral fluorinated pyrimidine based chemotherapy may have
been due to restoration of immunity in patients who could have been immunosuppressed due to
surgery and chemotherapy (Sakamoto et al., 2006). The mechanism of this effect is possibly via
action of PSK on a toll-like receptor initiating a signalling cascade involving T helper 1 cells
which induce IL-2 and IFN- and then activate natural killer cells. This sequence of signalling
cascades has recently been described in the modulation of innate immunity of Agaricus blazei
(Ab) (Hetland et al., 2011), although intake of 5% Ab over 4 weeks by male Wistar rats did not
confirm chemopreventive activity on the initiation stage of rat colon carcinogenesis (Ziliotto et
al., 2008, Ziliotto et al., 2009).
A clinical study of healthy volunteers reported that Ganoderma lucidum did not affect their
immune functions, but a subsequent open-labeled study (i.e. not double-blind or placebo
controlled) evaluating water-soluble G. lucidum polysaccharides (Ganopoly) in patients with
advanced colorectal cancer reported that treatment with Ganopoly tended to increase
mitogenic reactivity to phytohemagglutinin. Larger double-blind trials are required to validate this
effect and further studies are needed to determine the mechanism of action, efficacy, and safety
of the water-soluble G.lucidum polysaccharides in cancer patients (Gao et al., 2005). A
randomized, placebo-controlled, double-blind clinical trial in which patients with colorectal
cancer were supplemented with Agaricus sylvaticus mushroom, orally, twice daily
(30mg/kg/day), for six months also suggested benefits in haematological and immunological
parameters and reduced glycemic levels in patients with colorectal cancer (Fortes et al., 2009).
These data suggest that mushrooms may have an immunostimulatory effect on
immunocompromised patients, but not in a normal, healthy population.
Several in vitro studies in HT-29 human colonic carcinoma cells with extracts from Ganoderma
lucidum (Hong et al., 2004), Agaricus bisporus lectin (ABL) (Yu et al., 1993) and other
mushrooms have reported pro-apoptotic effects with no associated cytoxicity. It has been
suggested that the pro-apoptotic effects in HT-29 cells is induced by an increase in the activity
of caspase-3 (Hong et al., 2004). More recent studies have suggested the pro-apoptotic effects
and inhibition of the growth of HT-29 colonic cancer cells is mediated through up-regulation of
the expression of pro-apoptotic proteins and down-regulation of anti-apoptotic proteins (Lee et
al., 2009c). The inhibition of proliferation has been shown to be reversible after removal of
43
(Agaricus bisporus) lectin (Yu et al., 1993) and the reversibility of the anti-proliferative effect was
associated with the release of the lectin from cancer cells after internalization (Yu et al., 2000).
5.1.1.3 Cervical, Ovarian, Endometrial Cancer

The effect of consumption of an extract from Agaricus blazei Murill Kyowa (ABMK), on
immunological status and quality of life has been studied in cancer patients undergoing
chemotherapy. One hundred cervical, ovarian, and endometrial cancer patients were treated
either with carboplatin plus VP16 or with carboplatin plus taxol every 3 weeks for at least three
cycles, with or without oral consumption of ABMK. The authors observed that natural killer cell
activity was significantly higher in the ABMK-treated group compared to the non-treated placebo
group (n = 61). However, no significant difference in lymphokine-activated killer and monocyte
activities was observed. Chemotherapy-associated side effects such as appetite loss, alopecia,
emotional instability, and general weakness were all reported to be improved by ABMK
treatment (Ahn et al., 2004).
Very little is known about the mechanisms involved in the effects of mushrooms or mushroom
extracts in cervical, ovarian and endometrial cancers, with only a small number of reports
suggesting anti-proliferative effects (Liu et al., 2009, Chen et al., 2010d) via an induction of
apoptosis (Ren et al., 2008a).
5.1.1.4 Gastric Cancer

A meta-analysis of the effect of immunochemotherapy with lentinan compared to chemotherapy
alone has been evaluated in patients with advanced gastric cancer across five randomised
controlled trials. Lentinan significantly prolonged overall survival but was possibly more effective
in patients with lymph-node metastasis than in non-node metastasis patients (Oba et al., 2009).
Natural polysaccharides isolated from Phellinus gilvus (PG) have been shown to decrease cell
proliferation and increase cell apoptosis in a dose-dependent manner in vitro in a model of
human gastric adenocarcinoma and also to lead to a marked inhibition of tumor growth and a
significant decrease in the incidence of peritoneal carcinomatosis (Bae et al., 2006). Antiproliferative (Chen et al., 2008) and pro-apoptotic effects (Shomori et al., 2009) in human gastric
cell lines also were reported for several mushroom extracts with both caspase-3 - dependent
(Jin et al., 2006) (Shomori et al., 2009) and independent signalling cascades being implicated
(Shomori et al., 2009).
44
5.1.1.5 Pancreatic Cancer / Solid Malignancies

Only one single trial on the effects of a mushroom-derived compound on pancreatic cancer in
humans has been reported. A Phase I trial and pharmacokinetic study of irofulven, a mushroomderived cytotoxin has been carried out in 46 patients with advanced solid malignancies. While
the highest dose used was not well tolerated (grade 4 neutropenia and renal toxicity), the
authors recommended a lower dose of irofulven (10.64mg/m2) as a 5-minute intravenous
infusion daily for 5 days every 4 weeks. The preliminary anti-tumor activity documented in a
patient with advanced pancreatic cancer and the positive pre-clinical anti-tumor effects
observed on intermittent dosing schedules support a need for further trials on irofulven. It should
be noted that the source of this compound (Omphalotus olearius) is not an edible mushroom
(Eckhardt et al., 2000).
5.1.1.6 Prostate Cancer

Human trials to date have shown that mushrooms and their extracts to be ineffective in the
treatment of clinical prostate cancer, although the treatments have been well-tolerated. A Phase
II clinical trial has assessed the efficacy and safety of mushroom mycelium extracts (4.5 g/day
for 6 months) in 74 patients with early stage prostate cancers. Patient ingestion compliance was
maintained near 100% during the course of the trial. The mushroom mycelium extract was an
ineffective treatment for reducing 50% or more the patient prostate specific antigen values
(Sumiyoshi et al., 2010).
A 6 month open-label study in 51 patients with prostate cancer that ingested either Senseiro,
containing extracts from the Agaricus blazei Murill mushroom, or Rokkaku Reishi, containing the
Ganoderma lucidum mushroom has reported no serious adverse effects, and no significant
anticancer effects were observed with the intake of these two mushroom supplements
(Yoshimura et al., 2010).
Trials with Ganoderma lucidum (Noguchi et al., 2008a, Noguchi et al., 2008b) and with a
polysaccharide/oligosaccharide complex obtained from a Shiitake mushroom extract (White et
al., 2002) showed no effect on prostate-specific antigen levels in patients with either lower
urinary tract symptoms or patients with prostate cancer respectively.
45
Supplemental amounts of a polysaccharide/oligosaccharide complex obtained from a Shiitake

mushroom extract have been evaluated for the ability to lower the prostate-specific antigen level
in patients (n=62) with prostate cancer. The data showed that the Shiitake mushroom extract
alone was ineffective in the treatment of clinical prostate cancer (White et al., 2002).
In other human trials, treatment with Senseiro (containing extracts from Agaricus blazei Murill)
and Rokkaku Reishi, (containing the Ganoderma lucidum mushroom) for 6 months in patients
with prostate cancer also failed to show a response in terms of serum prostate-specific antigen
(Yoshimura et al., 2010), while a Phase II human trial of 74 early prostate cancer patients
reported a mushroom mycelium extract to be ineffective in reducing by 50% or more the patient
prostate specific antigen values (Sumiyoshi et al., 2010).
These human trial outcomes do not support in vitro mechanistic studies, where several
mushrooms and their extracts have been reported to inhibit proliferation of human prostate
cancer cell lines. An Agaricus blazei extract (with a high ratio of beta-glucan) inhibited cell
proliferation in both androgen-dependent and androgen-independent prostate cancer cell lines
via an apoptotic pathway, with activities of caspase 3 and DNA fragmentation being enhanced
the most in androgen-independent PC3 cells (Yu et al., 2009a). Beta-glucan from Grifola
frondosa (Maitake) has a cytotoxic effect on human androgen-independent prostatic cancer PC3 cells in vitro, leading to apoptosis (Fullerton et al., 2000), while a recent study has also
suggested that a Phellinus linteus extract is able to sensitize advanced prostate cancer cells to
apoptosis in athymic nude mice (Tsuji et al., 2010).
Inhibition of proliferation in a dose- and time-dependent manner and induction of apoptosis in
PC-3 human prostate cancer cells by Ganoderma lucidum (Jiang et al., 2004b) has been
determined to be caused by the inhibition of constitutively active AP-1 in prostate cancer cells,
resulting in the down-regulation of secretion of vascular endothelial growth factor and
transforming growth factor beta (TGF-beta1) from PC-3 cells, and G. lucidum inhibits prostate
cancer-dependent angiogenesis by modulation of MAPK (mitogen activated protein kinase) and
Akt signaling (Stanley et al., 2005).
The mechanisms by which mushrooms and their extracts affect prostate cancer cells appear to
be multi-modal with gene network analysis of studies with Agaricus bisporus identifying
alterations in networks involved in apoptosis, growth and proliferation, lipid metabolism, the TCA
cycle and immune responses (Adams et al., 2008).
46
5.1.2 Anti-Microbial Properties

Anti-microbial effects of a large number of mushroom varieties and mushroom components on
both gram-positive and gram-negative bacteria have been confirmed via in vitro studies. A small
number of animal studies have been undertaken and the data suggest that the anti-microbial
effects in vivo may be mediated by effects on the immune system. Initial studies in humans
suggested anti-microbial properties of extracts from Agaricus blazei Murill and Ganoderma
lucidum, although these studies did not have adequate controls in the experimental design, and
therefore such effects have not yet been scientifically validated in humans.
Patients on dialysis are at high risk of infection, including fungal infections. Anti-beta-glucan
antibody participates in the immune response to fungal cell wall beta-glucan. The anti-betaglucan antibody titer has been shown to be lower in dialysis patients than in healthy volunteers,
and long-term dialysis patients showed lower anti-beta-glucan antibody titers than short-term
dialysis patients. The titer of anti-beta-glucan antibody as a recognition molecule of beta-glucan
was low in dialysis patients compared to healthy volunteers, which may in part explain the
sensitivity to infection of dialysis patients. Although not proven, there is a possibility that
mushroom consumption may assist in a preventative role for fungal infection in dialysis patients
(Ishibashi et al., 2011).
A prospective controlled trial in humans (n=52) has evaluated the in vivo efficacy of the
mushroom Tremella mesenterica Ritz.:Fr. (higher Basidiomycetes) on eradication of
Helicobacter pylori. Ten-day treatment was not found to be effective in vivo in eradicating
Helicobacter pylori, whether given with or without omeprazole, although the brief treatment
period was a limitation of the study (Lachter et al., 2012).
A very small one-year open-label (not double-blind or placebo-controlled) pilot study reported
that intake of Agaricus blazei Murill (AbM) extract (1500 mg daily) over 12 months improved
liver function in patients with hepatitis B, determined by a decrease in the mean level of
aspartate aminotransferase and alanine aminotransferase decreased from 246.0 to 61.3 IU/L
and 151.0 to 46.1 IU/L, respectively (Hsu et al., 2008a). The initial observation seems to
indicate a potential benefit of AbM extract in normalizing liver function of patients with hepatitis
B, although clearly larger and controlled studies are required to confirm such effects.
47
5.1.3 Anti-Viral Properties

Proteins, peptides and polysaccharopeptides from mushrooms have been reported to inhibit
human immunodeficiency virus type 1 (HIV-1) reverse transcriptase and protease, the two
enzymes of importance to the life cycle of HIV. Inhibitory effects on hepatitis B and herpes
simplex virus type 1 have also been reported. The anti-viral effects of mushrooms do not seem
to be related to viral adsorption or virucidal effects (i.e. they do not kill the virus), however a
number of studies have reported inhibitory effects at the initial stage of virus replication (Faccin
et al., 2007).
Two phase I/II placebo-controlled trials in 98 HIV-positive patients were completed using
lentinan, a -glucan isolated from Lentinus edodes (Shiitake mushroom) (Gordon et al., 1998).
The studies reported generally good tolerability of lentinan with observed side effects being
mainly mild, particularly when infusion was carried out over a 30 minute period. In the first study,
where administration was over a 10 minute period, there were 9 side effects severe enough to
be reported to the FDA (one case each of anaphylactoid reaction, back pain, leg pain,
depression, rigor, fever, chills, granulocytopenia and elevated liver enzymes) with four patients
discontinuing therapy because of side effects. In the second study, where infusion was over a
30 minute period, there were no side effects reportable to the FDA but there were four drop-outs
due to side effects or personal preference. Most side effects resolved promptly after the
discontinuation of medication, and all of them were relieved within 24 hours. The small number
of patients in the study groups meant the data on possible increases in CD4 cell and neutrophil
activity were inconclusive (Gordon et al., 1998).
5.1.4 Asthma
A Cordyceps extract has recently been evaluated in asthmatic children during remission stage
(Sun et al., 2010). The Cordyceps extract inhibited the proliferation and differentiation of Th2
cells and reduced the expression of related cytokines by down-regulating the expression of
GATA-3 mRNA and up-regulating the expression of Foxp3 mRNA in peripheral blood
mononuclear cells. The extract was able to alleviate the chronic allergic inflammation by
increasing the level of interleukin-10.
48
5.1.5 Cardiovascular Health

A human intervention study has evaluated the cholesterol lowering properties of an Oyster
mushroom (Pleurotus ostreatus) diet. Twenty subjects (9 male, 11 female; 20-34 years) were
randomized to take either one portion of soup containing 30 g dried oyster mushrooms or a
tomato soup as a placebo daily for 21 days. The Oyster mushroom soup decreased
triacylglycerol concentrations (0.44 mmol/L) and oxidized low density lipoprotein levels (7.2
U/mL) significantly, and showed a significant tendency in lowering total cholesterol values (0.47
mmol/L; p = 0.059). No effects on low density lipoprotein and high density lipoprotein levels
were observed (Schneider et al., 2011).
Oyster mushroom consumption by 89 diabetic patients significantly reduced systolic and
diastolic blood pressure, total cholesterol and triglycerides, with no significant change in body
weight and no deleterious effects on liver or kidney function (Khatun et al., 2007). Another study
in 90 female volunteers demonstrated a weight-controlling and hypolipidemic effect of proteinbound polysaccharides from the mycelia of Agaricus blazei and Lentinus edodes, via a
mechanism involving absorption of cholesterol (Kweon et al., 2002). However, a double-blind,
placebo-controlled, cross-over intervention study in adults (n=18; ages 2252 years) of a
commercially available encapsulated Lingzhi preparation (equivalent to 13.2g fresh
mushroom/d) over 4 weeks failed to show any change in biomarkers for coronary heart disease
risk (Wachtel-Galor et al., 2004).
The bioavailability of ergothioneine from Agaricus bisporus, that functions as an antioxidant in
mushrooms has been determined in a pilot study in healthy men (n=10) using a randomized,
cross-over, dose-response, postprandial time-course design. Ergothioneine was bioavailable
after consuming mushrooms (8g and 16g) and a trend in the postprandial triglyceride response
indicated that there was a blunting effect after both the 8g and 16g ergothioneine doses were
compared with the control (0g dose). Ergothioneine from A. bisporus mushrooms was therefore
bioavailable as assessed by red blood cell uptake postprandially, and consumption was
associated with an attenuated postprandial triglyceride response (Weigand-Heller et al., 2012).
A single-arm, open-label, proof-of-concept study of 8 weeks duration has been completed
which assessed the safety and efficacy of Pleurotus ostreatus (15 g/day orally) in HIV-infected
individuals taking antiretroviral therapy that induced hyperlipidemia. Pleurotus ostreatus at the
concentration taken in this study did not lower non-HDL cholesterol in HIV patients with
antiretroviral treatment-induced hypercholesterolemia. Small changes in HDL and triglycerides
were not of a clinical magnitude to warrant further study (Abrams et al., 2011). The effects of
49
mushroom consumption on biomarkers of cardiovascular disease risk have recently been

reviewed (Guillamon et al., 2010).
5.1.6 Cognition / Brain Health

Although preliminary, data showing protective effects of mushrooms (Hericium erinaceum) on
beta-amyloid peptide toxicity (Kawagishi and Zhuang, 2008) in the brain and mild cognitive
impairment (both precursors to dementia) appeared promising. Preliminary human trials with
Hericium erinaceum derivatives showed efficacy in patients with dementia in improving the
Functional Independence Measure (FIM) score or retarding disease progression (Kawagishi and
Zhuang, 2008), while a double-blind, parallel-group, placebo-controlled trial with oral
administration of Yamabushitake (Hericium erinaceus) to 50 to 80-year-old Japanese men and
women diagnosed with mild cognitive impairment reported significantly increased cognitive
function scores compared to placebo during intake, but the scores decreased significantly
following termination of the intake (Mori et al., 2009).
A large epidemiological study (The Hordaland Health Study) of 2031 elderly subjects (aged 7074 years; 55% women) recruited from the general population in Western Norway has examined
the relationship between intake of different plant foods and cognitive performance in elderly
individuals in a cross-sectional study design. The cognitive test battery covered several
domains (Kendrick Object Learning Test, Trail Making Test - part A, modified versions of the
Digit Symbol Test, Block Design, Mini-Mental State Examination and Controlled Oral Word
Association Test). A validated and self-reported food frequency questionnaire was used to
assess habitual food intake. Subjects with intakes of >10th percentile of fruits, vegetables, grain
products and mushrooms performed significantly better in cognitive tests than those with very
low or no intake, with the dose-dependent association being linear for mushrooms (Nurk et al.,
2010).
A case-controlled study of 249 patients with diagnosed Parkinsons Disease (PD) and controls
without neurodegenerative diseases (n = 368) has assessed dietary intake during the preceding
1 month using a validated, self-administered diet history questionnaire. Three dietary patterns
were identified: 'Healthy', 'Western' and 'Light meal' patterns. After adjustment for potential nondietary confounding factors, the Healthy pattern, characterized by a high intake of vegetables,
seaweed, pulses, mushrooms, fruits and fish, was inversely associated with the risk of PD with
a border-line statistical significance (P = 0.06). No associations with PD were detected for the
other two dietary patterns (Okubo et al., 2011). While the data from this case-control study
suggest a dietary pattern consisting of high intakes of vegetables, seaweed, pulses,
50
mushrooms, fruits and fish may be associated with a decreased risk of PD, the strength of the
association is modest and any such effects would need to be confirmed in other studies with
greater statistical power in the study designs.
A human study of 30 females has investigated the clinical outcomes of 4 weeks of intake of
Hericium erinaceus cookies versus placebo cookies on menopause, depression, sleep quality
and indefinite complaints, using the Kupperman Menopausal Index (KMI), the Center for
Epidemiologic Studies Depression Scale (CES-D), the Pittsburgh Sleep Quality Index (PSQ1),
and the Indefinite Complaints Index (ICI). Each of the CES-D and the ICI score after the H.
erinaceus intake was significantly lower than at the start of the trial. "Concentration", "irritating"
and "anxious" tended to be lower than the placebo group (Nagano et al., 2010, Shimizu et al.,
2010). While the results point towards a possible reduction of depression and anxiety in the
study group with H. erinaceus intake, larger studies with greater statistical power are required
to confirm such outcomes.
5.1.7 Constipation
Constipation is one of the most prevalent gastrointestinal complaints and high fiber intake is
recommended as an initial therapy for constipation. Ear mushrooms (Auricularia) are known to
have higher fiber contents (by ~50%) than other mushroom varieties. In patients with functional
constipation, fiber supplements using ear mushrooms have been shown to significantly improve
constipation related symptoms without serious side effects (Kim et al., 2004b).
5.1.8 Dental Health

A clinical trial in 30 volunteers has been undertaken over 11 days in which a low molecular
mass (LMM) fraction of an aqueous extract of Lentinus edodes (Shiitake) was evaluated as an
oral mouthrinse. The mushroom extract was evaluated against Listerine and a placebo (water).
Statistically significant differences were obtained for the plaque index on day 12 in subjects
treated with mushroom versus placebo, while for the gingival index significant differences were
found for both mushroom versus placebo and mushroom versus Listerine. Decreases in total
bacterial counts and in counts of specific oral pathogens were observed for both mushroom
extract and Listerine in comparison with placebo. The data suggest that this mushroom extract
may prove beneficial in controlling dental caries and/or gingivitis/periodontitis (Signoretto et al.,
2011). A fraction from Shiitake has also been shown to have a strong inhibitory effect on dentin
51
demineralization and induce microbial shifts that could be associated with oral health (Zaura et
al., 2011).
5.1.9 Diabetes
A large number of animal studies, using both normal and diabetic animals, have demonstrated a
hypoglycaemic effect of mushrooms and mushroom components. This effect appears to be
mediated via mushroom polysaccharides (possibly both - and -glucans) via a direct
interaction with insulin receptors on target tissues, although this mechanism remains to be
confirmed.
A randomized, double-blinded, and placebo-controlled clinical trial (n=72) showed that Agaricus
blazei Murill supplementation in combination with metformin and gliclazide improved insulin
resistance in these subjects. An increase in adiponectin concentration after Agaricus blazei
Murill extract consumption for 12 weeks may be the mechanism that resulted in the reported
effect (Hsu et al., 2007). Clinical investigation in diabetic patients (n=89) has also shown that
Oyster mushroom consumption significantly reduced systolic and diastolic blood pressure,
lowered plasma glucose, total cholesterol and triglycerides significantly, with no significant
change in body weight, and no deleterious effects on liver or kidney function (Khatun et al.,
2007). These results in humans mirror the decreases in plasma glucose, cholesterol and
triglyceride concentrations following Agaricus bisporus consumption observed in rats (Jeong et
al., 2010) and the reduction in blood pressure in Zucker fatty rats following oral administration of
Maitake mushroom fractions (Talpur et al., 2002).
The consistency between the effects of the mushroom extracts in diabetic animal models
described later in this report and preliminary data from human trials, which mirror decreases in
plasma glucose, blood pressure, cholesterol and triglyceride concentrations, strengthens the
level of evidence for anti-diabetogenic effects of the studied mushrooms and their extracts.
5.1.10 DNA Damage

The antioxidant properties of Ganoderma lucidum (Lingzhi or Reishi) and its effects on DNA
damage and repair in lymphocytes have been evaluated in a small cross-over human
intervention study with 7 healthy adults. Plasma total antioxidant power and the effect on
lymphocyte DNA damage and repair were assessed before and after each treatment of a single
dose (3.3 g) of G. lucidum or water (control). G. lucidum caused an acute increase in plasma
52
antioxidant power, but did not significantly affect the level or rate of repair in lymphocytic DNA
suggesting that the bioavailable antioxidants absorbed from G. lucidum have no effect on DNA
resistance to oxidative stress or repair in vivo (Wachtel-Galor et al., 2010).
5.1.11 Hepatitis
Clinical effects and safety evaluation of Agaricus Blazei Condensed Liquid (Agaricus Mushroom
Extract; ABCL) administered to human volunteers (10 male, 10 female) with chronic C-type
hepatitis orally twice per day for 8 weeks reported no toxicological or other side effects (Inuzuka
and Yoshida, 2002). A series of trials have evaluated Ganoderma lucidum on cancer, Type II
diabetes, coronary heart disease, chronic hepatitis B, and neurasthenia. Treatment with
Ganopoly for 12 weeks showed hypoglycemic activity and produced some anti-viral and liver
protective effects in patients with chronic hepatitis B infection. However, the same treatment
regimen did not result in any objective response in late-stage cancer patients (Zhou et al.,
2005). Overall, the findings suggest that Ganopoly may have some pharmacological activities,
although clinical proof is lacking.
5.1.12 Immune Function

Numerous studies have described the effects of mushrooms and mushroom extracts on
immune function with implications for inhibiting tumor growth. Some of the more efficacious
compounds reported are the 1,6-branched 1,3--glucans, thought to inhibit tumor growth by
stimulating the immune system via effects on NK cells, macrophages and via T cells and their
cytokine production. More recent work has implicated polysaccharides with varying sugars and
some are - rather than -glucans. Furthermore, mushroom proteins, terpenes and furans have
also been implicated in immune function. While considerable in vitro data exists, in vivo studies
are few and the limited clinical studies that have been carried out have been with small numbers
of patients and have often been poorly controlled.
A systematic review of human clinical trials has concluded that numerous dietary
polysaccharides, particularly glucans, appear to elicit diverse immunomodulatory effects in
animal tissues, including the blood, GI tract and spleen. Structure-function relationships of betaglucans are of particular importance in their immunomodulatory effects (Thompson et al., 2010).
Glucan extracts from the Trametes versicolor mushroom have been shown to improve survival
and immune function in human randomised clinical trials of cancer patients. Glucans,
arabinogalactans and fucoidans elicited immunomodulatory effects in controlled studies of
53
healthy adults and patients with canker sores and seasonal allergies. This systematic review
provides a high level of evidence for these effects (Ramberg et al., 2010).
A polysaccharide extract from Grifola frondosa (Maitake extract) has shown immunomodulatory
effects in a phase I/II dose escalation trial in post-menopausal breast cancer patients (n=34). No
dose-limiting toxicity was encountered and there was a statistically significant association
between Maitake and immunologic function. The dose-response curves for many endpoints
were non-monotonic with intermediate doses having either immune enhancing or immune
suppressing effects in peripheral blood compared with both high and low doses (Deng et al.,
2009). Another clinical trial in breast cancer patients (n=82) evaluating the immunomodulatory
effects of Yunzhi-Danshen capsules (Yunzhi (Coriolus versicolor); Danshen (Salvia miltiorrhiza))
showed significantly elevated B-lymphocytes in patients with breast cancer after taking YunzhiDanshen capsules, while plasma sIL-2R concentration was significantly decreased (Wong et al.,
2005).
A randomized, double-blind, placebo-controlled trial has evaluated the effects of Agaricus
blazei Murrill intake (900 mg/day for 60 days) on serum levels of interleukin-6 (IL-6), interferongamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) in 57 community-living
elderly women. After 60 days, no changes from baseline were detectable for any parameter in
either the placebo (n=29) or the mushroom (n=28) group (Lima et al., 2012).
Prolonged and exhausting physical activity causes numerous changes in immunity and
sometimes transient increases the risk of upper respiratory tract infections (URTIs). A double
blind, placebo-controlled study has investigated the effect of pleuran, an insoluble beta-(1,3/1,6)
glucan from mushroom Pleurotus ostreatus, on selected cellular immune responses and
incidence of URTI symptoms in athletes. Fifty athletes were randomized to pleuran or placebo,
taking pleuran or placebo supplements during 3 months. Incidence of URTI symptoms together
with characterization of changes in phagocytosis and natural killer (NK) cell count was
monitored.P leuran significantly reduced the incidence of URTI symptoms and increased the
number of circulating NK cells. In addition, the phagocytosis process remained stable in pleuran
group during the study in contrast to placebo group where significant reduction of phagocytosis
was observed. These findings indicate that pleuran may serve as an effective nutritional
supplement for athletes under heavy physical training. The mechanisms of pleuran function are
yet to be determined (Bergendiova et al., 2011). In a similar double-blind pilot study, 20 elite
athletes were randomized to beta-glucan (n=9) or placebo ( n=11); these groups consumed 100
mg of beta-glucan (Imunoglukan) or placebo supplements, respectively, once per day for 2
months. At the end of the supplementation period, the athletes underwent a 20 min intensive
54
exercise session. A 28% reduction in natural killer (NK) cell activity below baseline was
observed in the placebo group during the recovery period (1 h after exercise), whereas no
significant reduction in NK cell activity was found in the beta-glucan group, and no significant
decrease in NK cell count was measured in the beta-glucan group during the recovery period.
Immune cell counts did not differ significantly between the groups. These results indicate that
insoluble beta-glucan supplementation from P. ostreatus may play a role in modulating
exercise-induced changes in NK cell activity in intensively training athletes (Bobovcak et al.,
2010).
Discrepancies in results have been reported between ex-vivo and in vivo studies. After
stimulation of whole blood from healthy volunteers ex vivo with 0.5-5.0% of a mushroom extract,
mainly containing Agaricus blazei Murill (AbM), a dose-dependent increase in all the cytokines
studied was seen, ranging from two to 399-fold (TNF). However, in vivo, in eight volunteers
who completed the daily intake (60 ml) of the AbM extract for 12 days, a significant reduction
was observed in levels of IL-1- (97%), TNF- (84%), IL-17 (50%) and IL-2 (46%). Another nine
cytokines remained unaltered (Johnson et al., 2009). The discrepancy in cytokine release ex
vivo and in vivo may partly be explained by the antioxidant activity of AbM in vivo and limited
absorption of its large -glucans across the intestinal mucosa to the reticuloendothelial system
and blood.
A double-blind randomized trial undertaken in mildly hypercholesterolemic subjects (n=56) to
examine the effects of -glucans from Agaricus bisporus reported that consumption of A.
bisporus -glucans lowered lipopolysaccharide-induced TNF production by 69% compared to
the control group, whereas no effect on IL-1 and IL-6 was observed. The authors suggested
that in vivo, alpha-glucans had lost their efficacy to stimulate the immune response as observed
in an in vitro mouse model (Volman et al., 2010b).
In healthy adults over 50 years of age, active hexose correlated compound (AHCC) enhanced
CD4(+) and CD8(+) T cell immune responses, taking at least 30 days to obtain such an effect,
with the effect continuing up to 30 days after discontinuing treatment with AHCC (Yin et al.,
2010). AHCC also promotes T helper (Th) 17 and 1 cell responses via inducing IL-1beta
production from monocytes in humans (Lee et al., 2012).
The synergistic effects of Cordyceps sinensis with the drug cyclosporine A in preventing
allograft rejection was recently reported in rats (Ding et al., 2009a) but a retrospectively study
by the same group has also evaluated the immunoregulatory effect of a dry powder preparation
of Cordyceps sinensis mycelia on humans after renal transplantation (Ding et al., 2009b). While
55
there was no significant difference in graft survival rate or occurrence of reject reaction,
treatment did effectively protect liver and kidney, stimulate hemopoietic function, improve
hypoproteinemia, as well as reduce the incidence of infection and the dosage of the drugs
cyclosporine A and tacrolimus used, and therefore, it may be useful for immunoregulation after
organ transplantation.
An extract (AndoSan) from Agaricus blazei Murill (AbM) has been shown to reduce blood
cytokine levels in healthy volunteers after 12 days of ingestion, pointing to an anti-inflammatory
effect. This extract also modulated cytokines in patients with ulcerative colitis (UC, n=10) and
Crohn's disease (CD, n=11) in which baseline concentrations for the (17) cytokines ebaluated in
the UC and CD patient groups were largely similar. Faecal calprotectin (a marker for
inflammatory bowel disease (IBD) was reduced in the UC group. Ingestion of an AbM-based
medicinal mushroom by patients with IBD resulted in decreased levels of pathogenic cytokines
in blood and calprotectin in faeces, suggesting anti-inflammatory effects (Forland et al., 2011).
The mechanisms for such effects are unclear, although an in vitro study by the same authors
with monocyte-derived dendritic cells showed that AbM did not induce increased synthesis of
Th2 or anti-inflammatory cytokines or the Th1 cytokine IL-12. but the AbM-based extract
resulted in increased production of proinflammatory, chemotactic and some Th1-type cytokines
(Forland et al., 2010).
The effect and safety of a soluble beta-glucan from Lentinus edodes mycelium, Lentinex (R), in
42 healthy, elderly subjects has recently been evaluated in a double blind, crossover, placebocontrolled trial (Gaullier et al., 2011) where two groups were given either 2.5 mg/day Lentinex
(R) orally or placebo for 6 weeks; then after a washout period of 4 weeks, the alternate
supplementation was given for 6 weeks. The changes in the number of B-cells were significantly
different between the groups. The number of NK cells increased significantly in both groups, but
there was no significant difference between the groups. The immunoglobulins, complement
proteins and cytokines measured were not altered. The safety blood variables (differential cell
count, liver function, kidney function, and other blood chemistry) were not influenced by
Lentinex (R), and the number, nature, and severity of adverse events were similar to placebo.
Lentinex given orally to elderly subjects was deemed to be safe and induced an increase in the
number of circulating B-cells (Gaullier et al., 2011).
Secretory immunoglobulin A (sIgA) acts as the first line of adaptive humoral immune defence at
mucosal surfaces. A randomised trial of 24 healthy volunteers has shown that consumption of
100 g of blanched Agaricus bisporus daily with a normal diet for 1 wk significantly accelerated
56
sIgA secretion, thereby indicating its effect on the improvement of mucosal immunity (Jeong et
al., 2011).
Reviews have been carried out on the immunobiology of mushrooms (Borchers et al., 2008), on
the immunomodulatory activities of mushroom polysaccharides (Cheung et al., 2011), and on
the health effects of beta-glucans in mushrooms (Rop et al., 2009, Rondanelli et al., 2009). A
recent systematic review of immunomodulatory dietary polysaccharides concluded that glucan
extracts from Trametes Versicolor improved survival and immune function in human
randomised controlled trials of cancer patients (Ramberg et al., 2010). The immunomodulatory
effects of Agaricus blazei Murill and resultant impacts on an array of health outcomes have
recently been reviewed (Hetland et al., 2011, Lima et al., 2011). A mini-review on how the
immunomodulatory actions of mushroom polysaccharides impact tumor cells has also been
published (Wong et al., 2011).
Many of the potential therapeutic effects of mushrooms and mushroom components on a variety
of diseases appear to be directly or indirectly mediated by enhancing natural immunity of the
host via effects on natural killer (NK) cells, macrophages, via balance of T cells and their
cytokine production, and via the activation of Mitogen Activated Protein Kinase (MAPK)
pathways (Kim et al., 2007a, Lin et al., 2009b). A recent study has also suggested that
branching of the -glucan chain is a requirement for immunostimulatory activity (Volman et al,
2010b).
5.1.13 Reproductive Health

An open trial with 80 patients with polycystic ovary syndrome at three clinics in Japan has been
undertaken. Seventy-two patients were randomly assigned to receive Maitake extract (SXfraction: MSX) or clomiphene citrate (CC) monotherapy for up to 12 weeks. Eighteen patients
who did not respond to MSX or CC were subjected to combination therapy of MSX and CC for
up to 16 weeks. Eight patients with documented history of failure to CC received combination
therapy from the beginning. Twenty-six patients in the MSX group and 31 in the CC group were
evaluated for ovulation. The ovulation rates for MSX and CC were: 76.9% (20/26) and 93.5%
(29/31), respectively by the patients (NS), and 41.7% (30/72) and 69.9% (58/83), respectively,
by the cycles. In the combination therapy, 7 of 7 patients who failed in MSX monotherapy and 6
of 8 patients who failed in CC monotherapy showed ovulation. The data suggest that the
Maitake extract described in this study may induce ovulation in patients with polycystic ovary
syndrome and may be useful as an adjunct therapy for patients who failed first-line treatment
with clomiphene citrate (Chen et al., 2010b).
57
5.1.14 Summary of Human Studies

In general, the growing amount of data from human clinical trials suggest that the mushrooms
and mushroom extracts tested are safe and generally well-tolerated. The most promising data
appear to be those indicating an inverse relationship between mushroom consumption and
breast cancer risk, although the majority of data are based on food frequency /diet recalls.
However, recent studies have suggested that an inhibition of aromatase activity, and a
subsequent reduction in estrogen, affecting estrogen receptor positive tumors may provide a
mechanism for these effects of mushrooms in breast cancer treatment. This mechanism has
been proposed in in vitro and animal trials, and more recently in a human trial of
postmenopausal women diagnosed with breast cancer. Recent evidence has also suggested
that the anti-aromatase compound is conjugated linoleic acid (CLA).
Although preliminary, data showing protective effects of mushrooms on beta-amyloid peptide
toxicity in the brain and mild cognitive impairment (both precursors to dementia and Alzheimers
Disease) are very exciting and warrant further research.
58
6. Anti-diabetogenic Properties
6.1 Animal model (mouse) studies
Aqueous extracts of various mushrooms have been shown to
possess hypoglycemic activity and anti-hyperglycemic activity
against diabetes-inducing compounds in obese and diabetic
animal models. An aqueous extract of Ganoderma lucidum
(0.03 and 0.3g/kg) lowered the serum glucose level in
obese/diabetic (+db/+db) mice after one week of treatment
through the suppression of hepatic PEPCK gene expression
(Seto et al., 2009). Aqueous extracts of Pleurotus pulmonarius also have been shown to
possess hypoglycemic activity (Badole et al., 2006), as well as having synergistic antihyperglycemic effects with acarbose (Badole and Bodhankar, 2007) in alloxan-induced
diabetic mice. A similar anti-hyperglycemic effect has been reported by Grifola frondosa
(Cui et al., 2009) and Coprinus comatus (Han and Liu, 2009) on an adrenaline-induced
increase in blood glucose in mice, although in this study, the same result was not
observed with Ganoderma lucidum and Grifola frondosa.
Extracellular polysaccharides (EPS) from Laetiporus sulphureus var. miniatus have been
shown to both stimulate insulin secretion (Hwang et al., 2008) and insulin sensitivity
possibly via regulation of lipid metabolism (Cho et al., 2007) in diabetic mouse models. A
polysaccharide isolated from Phellinus linteus reportedly inhibited the development of
autoimmune diabetes by regulating cytokine expression in non-obese diabetic mice (Kim
et al., 2010c). The hypoglycemic potential of EPS was also confirmed by histopathological
examination that showed that EPS administration is able to restore impaired kidneys to
almost normal architecture (Hye-Jin et al., 2007) as well as pancreatic islets of Langerhans
(Yamac et al., 2008) in streptozotocin-induced rats.
Intake of Pleurotus eryngii (5% supplementation with a normal diet) has been shown to
decrease plasma glycated haemoglobin and serum glucose levels in a diabetic (db/db)
mouse model. Intake of Pleurotus eryngii also significantly reduced the homeostasis
model measurement of insulin resistance, total cholesterol and triglyceride, and increased
high density lipoprotein (HDL)-cholesterol levels demonstrating hypoglycaemic and
hypolipidemic effects and an improvement in insulin sensitivity in this mouse model
(Jung-In et al., 2010, Kim et al., 2010d). A hypolipidemic effect of Pleurotus eryngii extract
59
has also been shown in fat-loaded mice and suggested to be due to low absorption of fat
caused by the inhibition of pancreatic lipase (Mizutani et al., 2010). A hypolipidemic effect
of Ganoderma lucidum (Leyss:Fr) Karst has also been demonstrated in a mouse model
(Rubel et al., 2011).
The structure and anti-tumour activity of polysaccharide fractions of the fruit body of
Agaricus brasiliensis have been studied in cold and hot water extracts (CWE and HWE)
on a mouse diabetic model (C57BL Ksj-db/db). Compared to the water administered
control group, the body weight, urinary glucose exclusion, urinary pH, blood glucose level,
and organs weight were comparable. The splenocytes of CWE administered mice
produced a higher concentration of interleukin-6. By megascopic and microscopic
examinations of renal sections, the number of the mice having abnormal kidney was 3/5
(control), 2/5 (HWE), and 0/5 (CWE) suggested the activity of the renal protection in the
cold water extract. The results suggested that the pharmacological action of the cold
water extract of A. brasiliensis is significantly stronger than that of the hot water extract
(Furukawa et al., 2006). Polysaccharides extracted from Inonotus obliquus (Pers.: Fr.)
Pilat (Aphyllophoromycetideae) have also been shown to have antihyperglycemic,
antilipidperoxidative, and antioxidant effects in alloxan-induced diabetic mice (Xu et al.,
2010).
The anti-diabetic effect of an alpha-glucan (MT-alpha-glucan) from the fruit body of
Maitake mushrooms (Grifola frondosa) on KK-Ay mice (a type 2 diabetes animal model)
has been evaluated. Treatment with MT-alpha-glucan significantly decreased the body
weight, level of fasting plasma glucose, glycosylated serum protein, serum insulin,
triglycerides, cholesterol, free fatty acid and malondialdehyde content in liver. Treatment
with MT-alpha-glucan significantly increased the content of hepatic glycogen, reduced
glutathione and the activity of liver superoxide dismutase and glutathione peroxidase.
Moreover, the insulin binding capacity to liver crude plasma membranes increased and
histopathological changes in the pancreas were ameliorated in the treatment group. The
data suggested that MT-alpha-glucan has an anti-diabetic effect on KK-Ay mice, which
may be related to its effect on insulin receptors by increasing insulin sensitivity and
ameliorating insulin resistance of peripheral target tissues (Lei et al., 2007).
60
6.2 Animal model (rat) studies

Beta-glucans and their enzymatically hydrolyzed oligosaccharides from Agaricus blazei
have anti-hyperglycemic, anti-hypertriglyceridemic, anti-hypercholesterolemic, and antiarteriosclerotic activity indicating overall anti-diabetic activity in diabetic rats. However, the
enzymatically hydrolyzed oligosaccharides have been shown to have around twice the
activity of -glucans with respect to anti-diabetogenic activity (Kim et al., 2005). Semipurified fractions of a submerged-culture broth of Agaricus blazei Murill were also reported
to reduce blood glucose levels in streptozotocin-induced diabetic rats (Oh et al., 2010).
The characterisation and efficacy of beta-glucans from different sources, including
mushrooms on hypoglycaemia in streptozotocin-induced diabetic rats has been evaluated
(Sandeep et al., 2011).
An aqueous extract of Agaricus blazei Muril administered daily starting 40 days after the
onset of streptozotocin-induced diabetes in Wistar rats assisted in the recovery of
pulmonary tissue of the rats. Pulmonary lipoperoxidation increased in the diabetic animals
compared to the control group, followed by a reduction in the A. Blazei-treated group.
iNOS was increased in the lung in diabetic rats and reduced in the A. Blazei-treated
group. The pulmonary tissue in diabetic rats showed oxidative alterations related to the
streptozotocin treatment. The A. Blazei treatment effectively reduced the oxidative stress
and contributed to tissue recovery (Di Naso et al., 2010).
Comatin, an inhibitor of the non-enzymatic glycosylation (NEG) reaction, purified from
Coprinus comatus fermentation broth and identified as 4,5-dihydroxy-2-methoxy-benzaldehyde. The blood glucose concentration of normal rats treated by comatin at 80 mg/kg
body weight was reduced from 5.14 mM to 4.28 mM in 3 h, while the concentrations of
fructosamine, triglycerides and total cholesterol in alloxan-induced diabetic rats were
significantly decreased, indicating that comatin could maintain a low level of blood glucose
and improve glucose tolerance (Ding et al., 2010).
Treatment with mushroom Pleurotus ostreatus extract has been suggested to reduce high
blood glucose level, genetic alterations (DNA fragmentation, chromosome aberrations)
and sperm abnormalities in streptozotocin-induced diabetic rats (Ghaly et al., 2011). A
hypoglycemic effect on streptozotocin-induced diabetic rats has also been demonstrated
by Agaricus bisporus (Sang Chul et al., 2010) and by polysaccharides from Laetiporus
sulphureus (Hwang and Yun, 2010). Furthermore, a hot water extract of Agaricus
bisporus, administered at 400 mg/kg body weight per day for 7 days resulted in a 29.68%
61
reduction of serum glucose levels, with serum insulin levels significantly increasing in
streptozotocin-induced diabetic rats. However, a most interesting effect of the treatment
was the increase in cellularity of the Langerhans islets of the pancreas and their apparent
repopulation with beta cells (Yamac et al., 2010).
Vanadium-enriched Cordyceps sinensis (VECS), has been hypothesized as a possible
treatment approach to both diabetes and depression, based on vanadium compounds
having an ability to imitate the action of insulin and C. sinensis having an antidepressantlike activity, and being able to attenuate a diabetes-induced increase in blood glucose
concentrations (Guo et al., 2010, Guo et al., 2011). However, the hypothesis remains to
be proven.
Agaricus bisporus has been shown to lower blood glucose and cholesterol levels in
streptozotocin (STZ)-induced diabetic and rats fed a hypercholesterolemic diet (Jeong et
al., 2010). The STZ-induced diabetic male Sprague-Dawley rats fed Agaricus bisporus
powder (200 mg/kg of body weight) for 3 weeks had significantly reduced plasma glucose
and triglyceride concentrations (24.7% and 39.1%, respectively), liver enzyme activities,
alanine aminotransferase and aspartate aminotransferase (11.7% and 15.7%,
respectively), and liver weight gain. In hypercholesterolemic rats, oral feeding of the
Agaricus bisporus powder for 4 weeks resulted in a significant decrease in plasma total
cholesterol and low-density lipoprotein (22.8% and 33.1%, respectively). A similar
significant decrease in hepatic cholesterol and triglyceride concentrations was observed
(36.2% and 20.8%, respectively). The decreases in total cholesterol, low-density
lipoprotein, and triglyceride concentrations were accompanied by a significant increase in
plasma high-density lipoprotein concentrations demonstrating significant hypoglycemic
and hypolipidemic activity in rats.
Lectins from Agaricus bisporus and Agaricus campestris have been shown to stimulate
insulin and glucagon release from isolated rat islets in the presence of 2 mM glucose.
Maximal stimulation of insulin release was reported at lectin concentrations above 58
g/mL (approximately 1 M). The lectin did not alter islet glucose oxidation to CO2 or
incorporation of [3H] leucine into trichloracetic acid-precipitable material, nor did it modify
rates of insulin secretion induced by 20 mM glucose. None of nine other lectins tested
stimulated insulin release, whereas stimulation of fat cell glucose oxidation was a general
property of the lectins. The data also suggested that lectin binding is essential for the
expression of insulin-releasing activity. The authors proposed that the specific interaction
between mushroom lectin and its receptors may lead to conformational changes in the
62
structure of the membranes of the islet A2- and B-cells that facilitate exocytosis (Ewart et
al., 1975).
The hypoglycaemic effect of exo-polymers (EPs) produced from submerged mycelial
cultures of several varieties of mushrooms on streptozotocin (STZ)-induced diabetic rats
have been investigated. The five experimental groups were fed with EPs (50mg/kg body
weight) for 7 days. Significant reductions in plasma glucose, total cholesterol, and
triglyceride levels were observed in rats fed with Lentinus edodes and Cordyceps militaris
EPs. Plasma glucose and total cholesterol were also reduced by administration of
Phellinus linteus EPs, but the triglyceride level was not changed significantly. The EPs of
the three mushroom species also demonstrated a marked reduction in the level of plasma
glutamate-pyruvate transaminase (GPT). The result demonstrates the hypoglycaemic
activity of EPs of three mushroom varieties in STZ-induced diabetic rats and suggests
some potential in the control of diabetes mellitus (Kim et al., 2001). Similarly, a
hypoglycaemic effect of exo- and endo-biopolymers produced by a submerged mycelial
culture of Ganoderma lucidum in streptozotocin-induced diabetic rats has also been
reported (Yang et al., 2004).
The hypolipidemic effect of exo-polymers produced in submerged mycelial cultures of
Hericium erinaceus (HE), Auricularia auricula judae (AA), Flammulina velutipes (FV),
Phellinus pini (PP), and Grifola frondosa (GF) has been investigated in dietary-induced
hyperlipidemic rats. The animals were administered with exo-polymers at the level of
100mg/kg body weight daily for four weeks. A hypolipidemic effect was achieved in all the
experimental groups, however, HE exo-polymer proved to be the most potent, significantly
reducing plasma triglyceride (28.9%), total cholesterol (29.7%), low-density lipoprotein
(LDL) cholesterol (39.6%), phospholipid (16.0%), and liver total cholesterol (28.9%) levels,
compared to the saline administered (control) group. The results demonstrate the
potential of HE exo-polymer in treating hyperlipidemia in dietary-induced hyperlipidemic
rats (Yang et al., 2002a).
A subsequent study by the same group, using higher concentrations (200mg/kg body
weight in streptozotocin-induced diabetic rats) of exo-polymers from a submerged
mycelial culture of Lentinus edodes has shown that the administration of the exo-polymer
reduced the plasma glucose level by as much as 21.5%, and increased plasma insulin by
22.1% compared to the control group. It was also shown to lower the plasma total
cholesterol and triglyceride levels by 25.1 and 44.5%, respectively (Yang et al., 2002c).
63
Oral administration of Maitake mushroom fractions has been shown to lower blood
pressure and fasting blood glucose of Zucker fatty rats, a model of insulin resistance and
type 2 diabetes mellitus. The authors concluded that specific fractions of Maitake
mushroom, alone or combined with other natural products such as bitter melon and
niacin-bound chromium, may be useful in the treatment of insulin resistance (Talpur et al.,
2002).
Enhanced insulin-hypoglycaemic activity (improvement in insulin sensitivity) has also been
reported in spontaneously hypertensive rats consuming a glycoprotein extracted from
Maitake mushrooms (Preuss et al., 2007).
The effects of fermented Chaga mushroom (Inonotus obliquus) powder on the lipid
concentrations and the activities of liver marker enzymes of serum in genetically diabetic
Otsuka Long-Evans Tokushima fatty (OLETF) rats have ben studied. Rats were fed a
semi-synthetic diet supplemented with 50g/kg Chaga mushroom powder (CM) or 50g/kg
fermented Chaga mushroom powder (FCM) for 8 weeks (26 to 34 weeks of age).
Nondiabetic Long-Evans Tokushima Otsuka (LETO) rats were used as age-matched nondiabetic control animals. Water consumption was significantly higher in the OLETF control
than the LETO rats. Water consumption in the FCM-fed OLETF rats tended to be less
than in both the OLETF control and CM-fed OLETF rats. Serum concentrations of
triglycerides and total cholesterol were significantly higher in the OLETF control rats than
in the LETO rats while within the OLETF rat groups, the consumption of FCM resulted in a
significantly lower serum triglyceride concentration and slightly lowered serum total
cholesterol concentration when compared to the OLETF control and CM-fed rats. The
livers of the OLETF CM-fed rats showed less fatty changes compared to the OLETF
control rats and fat deposition in the hepatocytes was nearly absent. The data suggested
that orally ingested fermented Chaga mushroom has a possible beneficial effect on the
complications known to occur in obesity-related non-insulin dependent diabetes mellitus
(NIDDM) OLETF rat (Cha et al., 2006).
An improvement of insulin resistance and insulin secretion by water extracts of Cordyceps
militaris, Phellinus linteus, and Paecilomyces tenuipes in 90% pancreatectomized rats has
also been reported (Choi et al., 2004b), while the presence of anti-hyperglycaemic,
insulin-releasing and insulin-like activity in Agaricus campestris in streptozotocin (STZ)induced diabetic mice has also been demonstrated (Gray and Flatt, 1998).
64
A hypoglycaemic effect of extracellular fungal polysaccharides (EPS) in STZ-induced

diabetic rats has been reported. The differential expression patterns of rat kidney proteins
from normal, STZ-induced diabetic, and EPS-treated diabetic rats, were analysed. A
histopathological examination showed that EPS administration restored the impaired
kidney in STZ-induced rats to almost normal architecture (Hye-Jin et al. 2007). Following
oral administration of exopolysaccharide produced from submerged mycelial culture of
Lentinus strigosus (Schwein.) Fr. (Family Polyporaceae) in STZ-induced diabetic rats,
their serum glucose levels were reduced by up to 21.1% at the dose of 150 mg/kg of body
weight. Plasma insulin levels of STZ-induced diabetic rats decreased compared to control
rats. The hypoglycaemic potential of the EPS was further supported by histological
observations of pancreatic islets of Langerhans (Yamac et al., 2008).
Submerged-culture mycelia and broth of Grifola frondosa have been shown to contain
bioactive components for improving glycaemic responses, such as decreases in serum
triglyceride, fructosamine, and blood glucose concentrations in male Wistar rats injected
with nicotinamide plus STZ (diabetic rats) (Lo et al., 2008). A similar study with
Ganoderma lucidum has reported both hypoglycaemic and anti-hyperglycaemic effects in
Wistar rats (Mohammed et al., 2007). Ganoderma lucidum polysaccharides have also
been shown to significantly and dose-dependently increase nonenzymic and enzymic
antioxidants, serum insulin level and reduce lipid peroxidation and blood glucose levels in
STZ-diabetic rats (Jia et al., 2009).
6.3 In vitro studies

Hispidin from Phellinus linteus exhibited quenching effects against DPPH radicals,
superoxide radicals, and hydrogen peroxide in a dose-dependent manner. Intracellular
reactive oxygen species scavenging activity of hispidin was approximately 55% at a
concentration of 30 M. In addition, hispidin was shown to inhibit hydrogen peroxideinduced apoptosis and increased insulin secretion in hydrogen peroxide-treated
pancreatic beta-cells indicating that hispidin may have anti-diabetogenic properties via
protection of pancreatic beta-cells from reactive oxygen species in diabetes (Jang et al.,
2010a).
65
6.4 Summary of Anti-Diabetogenic Properties

A large number of animal studies, in both normal and diabetic animal models, have
confirmed the hypoglycaemic effects of mushrooms and mushroom components. The
hypoglycaemic effects appear to be mediated via mushroom polysaccharides (possibly
both alpha- and beta-glucans) via a direct interaction with insulin receptors on target
tissues, although this mechanism remains to be confirmed. The efficacy of medicinal
mushrooms (as a whole rather than for individual varieties) for glucose control in diabetes,
including the inhibition of glucose absorption, protection of beta-cell damage, increase of
insulin release, enhancement of antioxidant defence, attenuation of inflammation,
modulation of carbohydrate metabolism pathway, and regulation of insulin-dependent and
insulin independent signalling pathways have recently been reviewed (Lo and Wasser,
2011).
7. Anti-microbial Properties
7.1 Animal model studies
Anti-bacterial effects of Agaricus blazei Murill (AbM)
have been demonstrated with the AbM extract being
protective against systemic Streptococcus
pneumoniae 6B infection in mice. The extract was
most effective when given 24h before inoculation but
it also had protective effects when given together
with challenge compared with control. The lack of an
antibiotic effect on pneumococci in vitro and increased levels of cytokines MIP-2 and TNF
in the serum of mice receiving AbM extract, indicated that the protective effect of AbM was
due to the involvement of the native immune system. The anti-infection properties of AbM
have been shown in vivo and the results suggest that AbM extract may be useful as an
additional prophylactic and possibly therapeutic treatment against bacterial infections in
humans (Bernardshaw et al., 2005a, Bernardshaw et al., 2005b).
A subsequent study by the same group has shown that an extract of Agaricus blazei Murill
can protect against lethal septicemia in a mouse model of faecal peritonitis. Bacterial
66
septicemia can occur during gastroenterological surgery. The putatively anti-infective

immunomodulatory action of Agaricus blazei Murill (AbM) has been studied in an
experimental peritonitis model in BALB/c mice. The mice were orally given an extract of
AbM or phosphate-buffered saline 1 day before the induction of peritonitis with various
concentrations of faeces from the mice. The state of septicemia, as measured by the
number of colony-forming units of bacteria in blood, and the survival rate of the animals
were compared between the groups. Mice that were orally treated with Agaricus blazei
Murill extract before bacterial challenge showed significantly lower levels of septicemia
and improved survival rates (Bernardshaw et al., 2006).

Numerous in vitro studies have clearly demonstrated activities against gram-positive and
gram-negative bacteria, yeasts and mycelial fungi, including dermatophytes and
phytopathogens (Jagadish et al., 2009, Soboleva et al., 2006, Hearst et al., 2009a),
including several foodborne pathogenic bacterial strains (Venturini et al., 2008). It has
been suggested that such antimicrobial effects of mushroom extracts may be indirect, with
a polysaccharide-rich fraction of Agaricus brasiliensis being shown to increase host
resistance against some infectious agents through stimulation of the microbicidal activity of
macrophages (Martins et al., 2008).
Antibacterial activity of an array of Australian basidiomycetous macrofungi collected
across Queensland, Australia have been evaluated using water, ethanol, and hexane
extracts of freeze dried fruiting bodies. Encouraging results were found for a number of
macrofungi in the genera Agaricus (Agaricaceae), Amanita (Amanitaceae), Boletus
(Boletaceae), Cantharellus (Cantharellaceae), Fomitopsis (Fomitopsidaceae),
Hohenbuehelia (Pleurotaceae), Lentinus (Polyporaceae), Ramaria (Gomphaceae), and
Strobilomyces (Boletaceae) showing good growth inhibition of Gram positive,
Staphylococcus aureus, Gram negative and Escherichia coli bacteria (Bala et al., 2011).
Similar screening for antimicrobial activity has been undertaken in 117 collections of
Australian macrofungi belonging to the mushroom genus Cortinarius with 13 species,
namely Cortinarius ardesiacus, C. archeri, C. austrosaginus, C. austrovenetus, C.
austroviolaceus, C. coelopus, C. [ Dermocybe canaria] 2, C. clelandii, C. [ D. kula], C.
memoria-annae, C. persplendidus, C. sinapicolor, C. vinosipes and forty seven collections
of un-described Cortinarius species exhibiting IC 50 values of 0.09 mg/mL against S.
aureus. In contrast, most or all collections of only four species, namely C. abnormis, C.
67
austroalbidus, C. [ D. kula], C. persplendidus, and eleven un-described Cortinarius

collections exhibited similar effects against P. aeruginosa (IC 500.09 mg/mL) (Beattie et
al., 2010).
Activity against the Gram-positive bacteria Staphylococcus aureus, has been
demonstrated in Volvariella volvacea strain R83, while Volvariella volvacea strain
ATCC62890 showed significantly less antimicrobial activity, but was reported to be a
source of antioxidants (da Silva et al., 2010b).
Studies with an aqueous extract of Agaricus brasiliensis S. Wasser et al. (=Agaricus
blazei Murrill sensu Heinem.) failed to show any anti-microbial effects against Salmonella
enterica serovar Typhimurium (Fantuzzi et al., 2011) nor on immunomodulatory properties
(Fantuzzi et al., 2010).
The effects of beta-glucans from Coriolus versicolor on phagocytic activity, nitric oxide
(NO), TNF-alpha production, and signaling of dectin-1, a well-known beta-glucan receptor,
in macrophages has been evaluated. Dectin-1 signaling, triggered by beta-glucans,
elicited TNF-alpha and NO-iNOS/eNOS production, and these molecules seem to act as
secondary molecules that cause eventual phagocytosis by macrophages. The findings
suggest that C. versicolor could be used as a nutritional supplement that may be useful in
the treatment of infectious disease (Jang et al., 2011b).
The mycelial culture of Ganoderma lucidum has been shown to be highly active against
human pathogenic bacteria Escherichia coli, Staphylococcus aureus, Klebsiella
pneumoniae and Pseudomonas aeruginosa, with E.coli having the highest susceptibility to
the mushroom mycelia (Ofodile et al., 2011). A recent report has suggested that the
presence of tannins and flavonoids may be responsible for the positive antibacterial
activity and antifungal activity of mushrooms against human pathogens (Parameswari and
Chinnaswamy, 2011).
Agaricus bisporus and Pleurotus sajor caju have been assayed in vitro for their antimicrobial activities using aqueous and organic solvent extracts. It has been shown that
Escherichia coli 390, Escherichia coli 739, Enterobacter aerogenes, Pseudomonas
aeruginosa and Klebsiella pneumoniae were most sensitive to aqueous, ethanol,
methanol and xylene extracts of these mushrooms (Tambekar et al., 2006). Ethanol
extracts of Agaricus bisporus have also been shown to have antibacterial activity against
68
both gram positive and gram negative bacteria, as well as anticandidal activity against
Candida albicans (Jagadish et al., 2009).
Extracts from fermentation broth and mycelium of 15 strains of Lentinus edodes have
been shown to be active against gram-positive and gram-negative bacteria, yeasts and
mycelial fungi, including dermatophytes and phytopathogens. The strains differed by the
set of the organisms susceptible to the action of the extracts. Strains of L. edodes
combining marked anti-bacterial properties and high yields of water soluble
polysaccharides were screened. The active compounds were detected by preparative thin
layer chromatography. Two were identified with UV and mass spectrometry as
lentinamycin B and erytadenine (lentinacin). Lentinamycin B was found to be the main
component responsible for the anti-bacterial activity of the L. edodes strains (Soboleva et
al., 2006).
The anti-microbial activity of the culture fluid of Lentinus edodes mycelium grown in
submerged liquid culture has been demonstrated against Streptococcus pyogenes,
Staphylococcus aureus and Bacillus megaterium. The substance responsible for the
activity was heat-stable and was suggested to be lenthionine, an anti-bacterial and antifungal sulphur-containing compound (Hatvani, 2001).
Three anti-bacterial compounds extracted by chloroform, ethylacetate or water from dried
Shiitake mushrooms (Lentinus edodes) have been reported to possess efficient antibacterial activities against Streptococcus spp., Actinomyces spp., Lactobacillus spp.,
Prevotella spp., and Porphyromonas spp. of oral origin. In contrast, other general bacteria,
such as Enterococcus spp., Staphylococcus spp., Escherichia spp., Bacillus spp., and
Candida spp. were relatively resistant to these compounds. The anti-bacterial activity of
chloroform extracts and ethylacetate extracts were relatively heat-stable, while the water
extract was heat-labile (Hirasawa et al., 1999).
The action of the juice of Shiitake mushrooms (L. edodes) at a concentration of 5% from
the volume of the nutrient medium was found to produce a pronounced anti-microbial
effect with respect to Escherichia coli O-114, Staphylococcus aureus, Enterococcus
faecalis, Candida albicans and to stimulate the growth of E. coli M-17. Bifidobacteria and
lactobacteria exhibited resistance to the action of L. edodes juice (Kuznetsov et al., 2005).
Two cuparene-type sesquiterpenes, enokipodins C (1) and D (2), have been isolated from
culture medium of Flammulina velutipes (Enoki), along with enokipodins A (3) and B (4).
69
All the metabolites showed anti-microbial activity against the fungus Cladosporium
herbarum, and gram-positive bacteria, Bacillus subtilis and Staphylococcus aureus
(Ishikawa et al., 2001).
Podaxis pistillaris (Podaxales, Podaxaceae, Basidiomycetes) was found to exhibit antibacterial activity against Staphylococcus aureus, Micrococcus flavus, Bacillus subtilis,
Proteus mirabilis, Serratia marcescens and Escherichia coli. In a culture medium of P.
pistillaris, three epidithiodiketopiperazines were identified by activity-guided isolation.
Based on spectral data their identity was established as epicorazine A(1), epicorazine
B(2) and epicorazine C (3, antibiotic F 3822), which have not previously been reported as
constituents of P. pistillaris (Al-Fatimi et al., 2006).
Aqueous extracts of Shiitake and Oyster mushrooms have been tested qualitatively
against a panel of 29 bacterial and 10 fungal pathogens. Shiitake mushroom extract had
extensive anti-microbial activity against 85% of the organisms tested, including 50% of the
yeast and mould species in the trial. This compared favourably with the results from both
the positive control (Ciprofloxacin) and Oyster mushroom, in terms of the number of
species inhibited by the activity of the metabolite(s) inherent to the Shiitake mushroom
(Hearst et al., 2009b).
A polysaccharide-rich fraction of Agaricus brasiliensis has been evaluated for candidacidal
activity, H2O2 and nitric oxide (NO) production, and expression of mannose receptors by
murine peritoneal macrophages. The treatment increased fungicidal activity and it was
associated with higher levels of H2O2, whereas NO production was not affected. The
treatment enhanced mannose receptor expression by peritoneal macrophages. The
results suggested that this extract can increase host resistance against some infectious
agents through stimulating the microbicidal activity of macrophages (Martins et al., 2008).
The anti-microbial activity of aqueous, methanol, hexane, and ethyl acetate extracts from
edible wild and cultivated mushrooms against nine foodborne pathogenic bacterial strains
(Escherichia coli O157:H7, Salmonella Enteritidis, Shigella sonnei, Vibrio
parahaemolyticus, Yersinia enterocolitica, Bacillus cereus, Clostridium perfringens,
Listeria monocytogenes, and Staphylococcus aureus) have been screened. Twenty-nine
of the 48 species tested had anti-microbial activity. Methanol, ethyl acetate, and aqueous
extracts accounted for 92.8% of the positive assays, whereas the hexane extracts
accounted for only 7.2%. Gram-positive bacteria were more sensitive than Gram-negative
bacteria to fungal extracts, and C. perfringens was the most sensitive microorganism.
70
Aqueous extracts from Clitocybe geotropa and Lentinula edodes had the highest antimicrobial activity against the bacterial strains tested (Venturini et al., 2008).
7.3 Summary of Anti-Microbial Properties

Anti-microbial effects of a large number of mushroom varieties and mushroom
components on both gram-positive and gram-negative bacteria have been confirmed via
in vitro studies. A small number of studies in animals have been undertaken and the data
suggest that the anti-microbial effects in vivo may be mediated by effects of the immune
system. A very small number of human studies have been completed, but the antimicrobial effects of mushroom consumption remains to be confirmed in humans.
8. Antioxidant Properties
A comparison has been undertaken of the antioxidant

properties and phenolic profile of the most commonly
consumed fresh cultivated mushrooms and their mycelia
produced in vitro: Agaricus bisporus (white and brown),
Pleurotus ostreatus (oyster), Pleurotus eryngii (king oyster)
and Lentinula edodes (shiitake). Of the mushrooms evaluated,
the mushroom species with the highest antioxidant potential
was Agaricus bispous (brown), with in vitro, L. edodes possessed the highest reducing
power. Generally, in vivo samples revealed higher antioxidant properties than their
mycelia obtained by in vitro techniques. There was no correlation between the studied
commercial mushrooms and the corresponding mycelia obtained in vitro (Reis et al.,
2012). Strong antioxidant properties have recently been described for a water-extractable
polysaccharide fraction from Lentinus edodes (Shiitake) (Chen et al., 2012a), while
aqueous extracts of Ganoderma lucidum (30.1%), Schizophyllum commune (27.6%), and
Hericium erinaceus (17.7%) also showed a relatively high Antioxidant Index (% relative to
quercetin) (Abdullah et al., 2012).
Antioxidant activity, determined by beta-carotene-linoleic acid, reducing power, DPPH,
ferrous-ion chelating abilities, and xanthine oxidase inhibitory activity have been
71
demonstrated in aqueous-, acetone- and methanol-extracts from the fruiting bodies of

Pleurotus eryngii (Alam et al., 2011a). Pleurotus eryngii and Auricularia auricula-judae
both exhibit a protective effect against H2O2 induced oxidative cell damage with a P.
eryngii methanolic extract also possessing the higher ferrous iron chelating ability (IC50 =
0.42 mg/ml) (Oke and Aslim, 2011).
An extract of Pleurotus ostreatus (200 mg/kg body weight), has been shown to increase
gene expression of the antioxidant enzyme catalase and reduce the incidence of free
radical-induced protein oxidation during aging in rats, thereby potentially protecting
against the occurrence of age-associated disorders that involve free radicals (Jayakumar
et al., 2010a). A further study by the same group also showed that administration of an
extract of P.ostreatus to aged rats resulted in a significant increase in the levels of
reduced glutathione (GSH) and elevated activities of glutathione S-transferase (GST),
glutathione reductase (GR), and glucose 6-phosphate dehydrogenase (G6PDH) in liver,
kidney, heart, and brain tissues of rats. The results suggest that this extract of P.
ostreatus can prevent the oxidation of GSH and protect its related enzymes during aging
(Jayakumar et al., 2010b). The in vitro and in vivo antioxidant effects of the oyster
mushroom Pleurotus ostreatus have recently been reviewed (Jayakumar et al., 2011).
Extracts prepared from the fruiting body of Flammulina velutipes with a high ergothioneine
content exhibited a stronger delay of the autoxidation activity of oxymyoglobin, whereas
extracts prepared from the spent culture medium of F. velutipes with higher phenolics
content showed more efficient antioxidant capacity against lipid oxidation. The amount of
ergothioneine was distributed highest in the inedible (base and mycelium) parts of the
mushroom. These results suggest that the inedible parts and spent culture medium of F.
velutipes could potentially be considered as a readily available source of natural
antioxidants (Bao et al., 2010). Ergothionine has been shown to have anti-oxidative/antiinflammatory properties in several edible mushrooms (Ito et al., 2011).
Antioxidant properties and antioxidant compounds of various extracts from dried Grifola
frondosa (Maitake) have been determined. Antioxidant activity was measured using
reducing power, DPPH and superoxide radical scavenging and ferrous ion chelation
activity assays. Phenols, flavonoids, ascorbic acid and alpha-tocopherol were found to be
the major antioxidant components in the various mushroom extracts examined. The EC50
values (<20 mg/ml) indicate that the G. frondosa extracts studied have potent
antioxidative activity (Jan-Ying et al., 2011).
72
Agaricus bisporus (Savoie et al., 2008), Ganoderma lucidum (Reishi), Phellinus rimosus,
Pleurotus florida and Pleurotus pulmonaris (Ajith and Janardhanan, 2007)(Ajith and
Janardhanan, 2007), Volvariella volvacea (Mathew et al., 2008), Thelephora ganbajun,
Thelephora aurantiotincta, Boletopsis grisea (Liu et al., 2004a) and others have been
reported to have significant antioxidant activities. Of particular interest is that the
antioxidant activity (free radical scavenging activity) along with total phenolic and flavonoid
concentration of Agaricus bisporus appears to be similar before and after boiling
(Jagadish et al., 2009). It has also been suggested that the antioxidant capacities of
mushrooms may have a potentially protective effect against a variety of disease states,
including some cancers (Matsuzawa, 2006) and irritable bowel disease (Najafzadeh et al.,
2007).
Antioxidant activity via inhibition of lipid peroxidation has been described in several
studies. The antioxidant effects of Hypsizygus marmoreus have been studied for peroxyl
and alkoxyl radicals by ordinary, non-tumour-bearing and tumour-bearing mice. Oral
administration of the fruit body of H. marmoreus exhibited potent anti-tumour or cancerpreventive effects and caused a significant decrease in lipid peroxide levels, which were
determined as thiobarbituric acid reactive substances. These results showed that the
intake of H. marmoreus fruit body could induce an antioxidant effect, and the increase of
antioxidant activity in the plasma of tumour-bearing mice was an important mechanism in
cancer prevention. It was also suggested that the mushroom might play a role in the
decrease of lipid peroxides through antioxidant activity induction (Matsuzawa, 2006).
Ethanol extracts of the mushroom Phellinus linteus have been shown to have antioxidant
activities comparable to vitamin C in scavenging the stable free radical 1,1-diphenyl-2picrylhyrazyl (DPPH). The extracts also inhibited lipid peroxidation (LPO) in a
concentration-dependent manner. The study also reported anti-angiogenic activities of
Phellinus linteus (Song et al., 2003).
A hot water extract from Ganoderma lucidum has been shown to have an antioxidative
effect against heart toxicity in mice. Ganoderma lucidum exhibited a dose-dependent
antioxidative effect on lipid peroxidation and superoxide scavenging activity in mouse
heart homogenate. Furthermore, this result indicated that heart damage induced by
ethanol showed a higher malonic dialdehyde level compared with heart homogenate
treated with Ganoderma lucidum. The authors concluded that this effect of Ganoderma
lucidum may protect the heart from superoxide induced damage (Wong et al., 2004).
73
A more recent study has examined the effects of an extract of Ganoderma lucidum for its
free-radical scavenging property and for effects on liver mitochondrial antioxidant activity
in aged BALB/c mice (50 and 250 mg/kg body weight for 15 days) (Cherian et al., 2009).
G. lucidum increased antioxidant status in liver mitochondria of aged mice compared with
the aged controls. The extract possessed significant 2,2-diphenyl-1-picrylhydrazil (DPPH),
2, 2'-azinobis (3-ethylbenzothiazolin-6-sulphonic acid) (ABTS) radical scavenging
activities and ferric reducing antioxidant power (FRAP) as well as superoxide and hydroxyl
radical scavenging activities.
In vitro evaluation of antioxidant activities of Auricularia auricular has also shown
significant inhibition of lipid peroxidation, as well as potent hydroxyl radical scavenging
activity when compared to catechin, while crude, boiled and ethanolic extracts were
shown to significantly increase nitric oxide (NO) production over the control (Acharya et
al., 2004). The natural mushroom pigment Norbadione A and three other pulvinic acids
have been shown to display very efficient antioxidant properties in comparison to
catechols, flavonoids, stilbenes, or coumarins (Habrant et al., 2009).
Antioxidant activity of submerged cultured mycelium extracts of higher basidiomycetes
mushrooms has recently been reported. Antioxidant properties were studied from 28
submerged cultivated mycelium Basidiomycetes strains of 25 species. Three solvents ethanol, water (culture liquid), and ethyl acetate were used for extraction. Water extracts
from Coprinus comatus, Agaricus nevoi, and Flammulina velutipes showed high
antioxidant activities (AA) at 2mg/ml. When the ethanol extracts were tested, the highest
AA were found in Agaricus nevoi, Omphalotus olearius, and Auricularia auricula-judae
extracts at a concentration of 2mg/ml. The AA of ethanol extracts from Agrocybe aegerita
and C. comatus increased from 46.6% to 82.7% and from 2.4% to 62.1%, respectively,
when the concentration of the extract increased from 2mg/ml to 4-8mg/ml with the authors
suggesting that the extracts could be suitable as antioxidative agents and bioproducts
(Asatiani et al., 2007a, Asatiani et al., 2007b).
Antioxidant activities of ten natural p-terphenyl derivatives from the fruiting bodies of three
edible mushrooms (Thelephora ganbajun, Thelephora aurantiotincta, Boletopsis grisea)
from China have also been reported (Liu et al., 2004b).
In vitro evaluation of antioxidant activities of Auricularia auricular has shown significant
inhibition of lipid peroxidation, and potent hydroxyl radical scavenging activity when
compared with the drug catechin. The IC50 value of crude, boiled and ethanolic extracts of
74
A. auricula represented 403, 510, and 373 g/ml respectively of hydroxyl radical
scavenging activity and 310, 572 and 398 g/ml respectively of lipid peroxidation, while
crude, boiled and ethanolic extracts were shown to significantly increase nitric oxide
production (664, 191 and 850 pmole/mg dry wt/h respectively) over the control (Acharya
et al., 2004).
Ganoderma lucidum (Reishi), Phellinus rimosus, Pleurotus florida and Pleurotus
pulmonaris have also been reported to have significant antioxidant activities (Ajith and
Janardhanan, 2007).
The antioxidative potency of commercially available mushrooms in Taiwan has been
studied. The order of inhibitory activity of mushroom extracts on oxidation in an emulsion
system was Agaricus bisporus > Hypsizigus marmoreus > Volvariella volvacea >
Flammulina velutipes > Pleurotus eryngii > Pleurotus ostreatus > Hericium erinaceus >
Lentinula edodes. In a thermal oxidative stability test, using lard, the order of antioxidative
activity of the mushroom extracts showed similar tendencies, except for the extract of
Lentinula edodes (Fui et al., 2002). Antioxidative activities of Flammulina velutipes extract
have also been reported to be able to stabilize the fresh colour of tuna meat during ice
storage (Bao et al., 2009).
8.1 Phenolic Content

Determination of the phenolic and organic acid contents of Agaricus brasiliensis as well as
the antioxidant activities of its fruiting bodies and its mycelia obtained from submerged
cultivation has shown the presence of 3 phenolic compounds (gallic acid, syringic acid
and pyrogallol) and 8 organic acids( benzoic, oxalic, malic, acetic, alpha-ketoglutaric,
citric, fumaric and trans-aconitic acids). All extracts possessed antioxidant properties. The
fruiting body extracts were more effective in the DPPH radical scavenging activity and lipid
peroxidation inhibition than the mycelia extracts. The mycelia extracts however were more
effective in the ABTS radical scavenging activity and ferrous ion chelating ability (Carvajal
et al., 2012).
The phenolic compounds, syringic acid and vanillic acid from Lentinula edodes mycelia
that have radical scavenging activity, have also been shown to have a hepatoprotective
effect on CCl4--induced liver injury in mice. The intravenous administration of syringic acid
and vanillic acid significantly decreased the levels of the transaminases, suppressed
75
collagen accumulation and significantly decreased hepatic hydroxyproline content, which

is the quantitative marker of fibrosis. Both of these compounds inhibited the activation of
cultured hepatic stellate cells, which play a central role in liver fibrogenesis, and
maintained hepatocyte viability. Syringic and vanillic acid may therefore play a role in the
suppression of hepatic fibrosis in chronic liver injury (Itoh et al., 2010).
Heat treatment of Shiitake (Lentinus edodes) significantly increases its antioxidant activity
and polyphenolic compounds. The polyphenolic content and antioxidant activities in
extracts has been shown to increase as heating temperature and time increased (100 and
121C for 15 or 30min). The free polyphenolic content in the extract heated at 121C for
30min was increased by 1.9-fold compared to that in the extract from the raw sample. The
2,2-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical and 1,1-diphenyl-2picrythydrazyl (DPPH) radical scavenging activities were increased by 2.0-fold and 2.2fold compared to the raw sample, respectively (Choi et al., 2006a). Thermostable
antioxidant activity has also been reported from Agaricus blazei Murill (Izawa and Inoue,
2004).
The antioxidant activities of two edible mushrooms (Lentinus edodes and Volvariella
volvacea) against lipid peroxidation have been shown to correlate with the phenolic
content in different sub-fractions of the mushroom extracts (Cheung and Cheung, 2005).
Similarly, significant correlation was found between the total phenolic content from the
fruiting bodies of Agrocybe aegerite and antioxidant activity in an ethyl acetate fraction
and its sub-fractions (Lo and Cheung, 2005). Extracts of Agaricus blazei, Agrocybe
cylindracea, and Boletus edulis have been shown to have significant antioxidant
properties with the naturally occurring antioxidant components including total tocopherols
(3.18-6.18mg/g) and total phenols (5.67-5.81mg/g) (Tsai et al., 2007).
Antioxidant polyphenols from the mycelial culture of the medicinal fungi Inonotus
Xeranticus and Phellinus Linteus have been isolated and identified as hispidin and its
dimers, 3,14'-bihispidinyl, hypholomine B, and 1,1-distyrylpyrylethan. These compounds
exhibit potent free radical scavenging activity (Jung et al., 2008).
The antioxidant capacity and total phenolic content of Agaricus brasiliensis in two stages
of maturity, young (YB) and mature (MB), have been evaluated with minor differences in
the composition of phenolic compounds being detected, but with similar antioxidant
activities, except for the chelating ability for ferrous ions, which was higher in MB than in
YB (Soares et al., 2009).
76
Total phenols have been shown to be the major antioxidant components in ethanolic
extracts in a variety of culinary and medicinal mushrooms (Tsai et al., 2008, Tsai et al.,
2009). The antioxidant properties in mushrooms decrease significantly with storage time,
with recommendations being made that mushrooms be stored at 4C for up to 6 days
(Tsai et al., 2008). DPPH (1,1-diphenyl-2-picrylhydrazyl) activities have also been shown
to significantly correlate with total content of phenolic compounds in a variety of edible and
medicinal mushrooms (Kim et al., 2008).
8.2 Ergothioneine
Ergothioneine is a native membrane-impermeable thiol compound that is specifically
accumulated in cells via the organic cation transporter OCTN1. In humans, OCTN1 and
ergothioneine have been implicated in the etiopathogenesis of autoimmune disorders.
Few foods contain ergothioneine, with highest concentrations detected in specialty
mushrooms, kidney, liver, black and red beans, and oat bran. Ergothioneine has been
reported to exhibit cell protection only against copper(II)-induced toxicity but is far less
potent than glutathione, indicting that ergothioneine is not involved in the intracellular
antioxidant thiol defence system (Ey et al., 2007).
L-ergothioneine is a biologically active antioxidant produced by certain fungal species and
mycobacterium. The precursors to the synthesis of L-ergothioneine are the amino acids
histidine, cysteine, and methionine. Supplementation with L-ergothioneine has been
shown to have a protective effect on the organs of rats against lipid peroxidation and to
conserve the consumption of endogenous glutathione and alpha-tocopherol (Deiana et al.,
2004).
The ergothioneine content of mushrooms has been reported to be in the range of 0.42.0mg/g (dry weight). White Agaricus bisporus contained the least ergothioneine and
portabellas (brown) contained the highest within the varieties of A. bisporus studied. The
specialty mushrooms tested (Lentinus edodes, Pleurotus ostreatus, P. eryngii, Grifola
frondosa) all contained a statistically significant greater amount of ergothioneine
compared to A. bisporus; however, no significant difference was found between the
specialty mushrooms studied (Dubost et al., 2006).
An ergothioneine derivative, -hydroxyergothioneine has been isolated from the
mushroom Lyophyllum connatum. Ergothioneine,N-hydroxy-N',N'-dimethylurea, and
77
connatin (N-hydroxy-N',N'-dimethylcitrulline) were also isolated. All the compounds

displayed the ability to scavenge free radicals, based on a 1,1-diphenyl-2-picrylhydrazyl
(DPPH) radical scavenging assay. The radical scavenging activity of hydroxyergothioneine was very similar to that of ergothioneine. -Hydroxyergothioneine
showed the greatest protective activity against carbon tetrachloride-induced injury in
primary culture hepatocytes (Kimura et al., 2005).
Protein supplement treatments during mushroom growth do not have a significant effect
on the amount of L-ergothioneine produced by mushrooms, but the addition of histidine to
compost has been reported to significantly increase the amount of L-ergothioneine.
Furthermore, L-ergothioneine was increased by up to 1.3mg/g dry weight in later flushes
by several stress factors placed on the mycelia, such as dry compost, indicating that Lergothioneine may be a stress factor. A postharvest shelf-life study has also demonstrated
that L-ergothioneine significantly decreased during postharvest storage for up to 6 days at
12C (Dubost et al., 2007).
8.3 Summary of Anti-Oxidant Properties

A recent (2012) comparison of the antioxidant properties and phenolic profile of the most
commonly consumed fresh cultivated mushrooms and their mycelia produced in vitro:
Agaricus bisporus (white and brown), Pleurotus ostreatus (oyster), Pleurotus eryngii (king
oyster) and Lentinula edodes (shiitake) have reported that Agaricus bispous (brown)had
the highest antioxidant potential in vitro, while L. edodes possessed the highest reducing
power. Significant antioxidant activities in vitro have been reported in several varieties of
mushrooms, with one study reporting antioxidant capacity compable to vitamin C. The
antioxidant activities appear to be related to the polyphenolic content. L-ergothioneine is a
biologically active antioxidant and its production in mushrooms can be enhanced by
addition of histidine to the growth medium/compost. Ergothioneine has been shown to
have anti-oxidative/anti-inflammatory properties in several edible mushrooms.
78
9. Anti-viral Properties
Extracts of Grifola frondosa (Maitake) have shown
activity against hepatitis B virus (Gu et al., 2006),
herpes simplex virus type 1 (HSV-1) replication in
vitro (Gu et al., 2007) and against the growth of
influenza A/Aichi/2/68 virus (Obi et al., 2008). The
effects of a mushroom-derived active hexose
correlated compound (AHCC) on the immune
response to influenza A virus (H1N1, PR8) infection
were shown to be dose dependent with low-dose AHCC supplementation improving the
response to influenza infection despite no effect on total NK cell cytotoxicity (Nogusa et al.,
2009). Extracts from Phellinus linteus also provided protection against variant H5N1
influenza viruses (Ichinohe et al., 2010).
Anti-viral activity of several mushroom extracts has been demonstated in vitro and in vivo
in animal models. A polysaccharopeptide from the Turkey Tail mushroom Trametes
(=Coriolus) versicolor was reported to inhibite HIV-1 reverse transcriptase and protease,
the two enzymes of paramount importance to the life cycle of the HIV (Tzi et al., 2006).
Anti-HIV-1 protease activity was also reported for lanostane triterpenes from Ganoderma
colossum (El Dine et al., 2008) and from Ganoderma sinense (Sato et al., 2009), while
nebrodeolysin from Pleurotus nebrodensis has been shown to possess anti-HIV-1 activity
in vitro (Lv et al., 2009). Lectins from Agaricus bisporus, Phaseolus vulgaris, Momordica
charantia, Ricinus communis and its constituent chains have been shown to inhibit HIV-1
reverse transcriptase (Wang and Ng, 2001). A ubiquitin-like protein from Pleurotus
ostreatus has also demonstrated inhibitory activity toward HIV-1 reverse transcriptase,
which could be enhanced by succinylation (Wang and Ng, 2000). The evidence for an
anti-viral effect of several mushroom extracts via inhibition of HIV-1 reverse transcriptase
and protease appears strong. A farnesyl hydroquinone, ganomycin I, isolated along with
ganomycin B, from Ganoderma colossum has been reported to inhibit HIV-1 protease with
IC50 values of 7.5 and 1.0 g/mL, respectively (El Dine et al., 2009). Ganomycin B
competitively inhibited the active site of the enzyme, with both compounds docking with
the HIV-1 protease crystal structure.
Incubation of peripheral blood cells PBCs and hepatoma HepG2 cells with a laccase
purified from oyster mushroom (Pleurotus ostreatus) which were then infected with
79
hepatitis C virus HCV did not protect the cells from HCV attack and entry, while direct
interaction between HCV and the laccase at the concentrations of 2.0 and 2.5 mg/ml led
to a complete inhibition of virus entry after seven days of incubation, however, the laccase
at 1.0 and 1.5 mg/ml did not display any blocking activity. The laccase was capable of
inhibiting HCV replication in infected HepG2 cells at 1.25 and 1.5 mg/ml after the first
dose of treatment for 4 days and at 0.75, 1.0, 1.25 and 1.5 mg/ml after the second dose of
treatment for another 4days (El-Fakharany et al., 2010). A laccase with HIV-1 reverse
transcriptase inhibitory activity has recently been isolated from fresh fruiting bodies of
Lentinus edodes (Sun et al., 2011), Lentinus tigrinus (Xu et al., 2012a) and Pleurotus
cornucopiae (Wong et al., 2010). A polysaccharide with antiproliferative, hypoglycemic,
antioxidant and HIV-1 reverse transcriptase inhibitory activities from the fruiting bodies of
the abalone mushroom Pleurotus abalonus has also been reported (Wang et al., 2011).
Schizolysin, a hemolysin from the split gill mushroom Schizophyllum commune has been
shown to inhibit HIV-1 reverse transcriptase with an IC50 of 1.8 M (Han et al., 2010).
Antiproliferative and HIV-1 reverse transcriptase inhibitory activities have also been
demonstrated from dried fruiting bodies of Hericium erinaceum (Li et al., 2010b), while
adenosine, iso-sinensetin and dimethylguanosine from fruiting bodies of Cordyceps
militaris have been shown to have antioxidant and HIV-1 protease inhibiting activities
(Jiang et al., 2011b).
A methanol extract of Phellinus linteus has been reported to inhibit the trafficking process
of Newcastle disease virus hemagglutinin-neuramidase, a viral glycoprotein, in virusinfected baby hamster kidney cells. The results suggested that P. linteus extract inhibits
viral glycoprotein expression on cell surfaces through inhibition of trafficking processes
rather than glycoprotein synthesis (Doseung et al., 2011).
Extracts of mycelia derived from edible mushrooms have been reported to be effective as
mucosal adjuvants for intranasal influenza vaccine against variant H5N1 influenza viruses
(Ichinohe et al., 2010).
Crude dichloromethane, ethanol, water, and polysaccharide extracts of Ganoderma
lucidum all suppressed HPV 16 E6, with the dichloromethane extract being the most
active. The extract of G. lucidum contained flavonoids, terpenoids, phenolics, and
alkaloids, although it is unknown which compounds in the extract were responsible for the
anti-viral effects (Lai et al., 2010).
80
Anti-tubercular activity and an inhibitory effect on Epstein-Barr virus activation of sterols

and polyisoprenepolyols from an edible mushroom, Hypsizigus marmoreus (Buna-shimeji)
have been reported. Seven sterols and eight polyisoprenepolyols, isolated from the nonsaponifiable lipid fraction of the dichloromethane extract of Hypsizigus marmoreus, have
been tested for their anti-tubercular activity against Mycobacterium tuberculosis strain
H37Rv using the Microplate Alamar Blue Assay (MABA). Six of the sterols and two of the
polyisoprenepolyols showed a minimum inhibitory concentration (MIC) in the range of 151mg/ml, while the others were inactive. The seven sterols and three polyisoprenepolyols
were further evaluated for their inhibitory effects on Epstein-Barr virus early antigen (EBVEA) activation induced by the tumour promoter 12-O-tetradecanoylphorbol-13-acetate
(TPA) in Raji cells. Two of the sterols showed a potent inhibitory effects while preserving
the high viability of the Raji cells (Akihisa et al., 2005).
Isolated polysaccharides (PLS) from the fruiting body of Agaricus brasiliensis (previously
named Agaricus blazei ss Heinem), also known as the sun mushroom, have been shown
to have anti-viral activity and were more effective when added during poliovirus infection.
The extracts had little effect on reducing viral adsorption and did not show any virucidal
effect, suggesting that they may act at the initial stage of the replication of poliovirus
(Faccin et al., 2007).
Anti-viral activities of Agaricus blazei Murill have been demonstrated against cytopathic
effects induced by western equine encephalitis (WEE) virus by the mycelial fractions but
not those of fruiting bodies (Sorimachi et al., 2001).
9.1 Summary of Anti-Viral Properties

Two Phase I/II trials in HIV-positive patients have been undertaken with lentinan, a betaglucan from Lentinus edodes. Some side effects were observed at the highest dosages
used, which were not present when infusion was undertaken over a shorter period.
Proteins, peptides and polysaccharopeptides from mushrooms have been reported to be
capable of inhibiting human immunodeficiency virus type 1 (HIV-1) reverse transcriptase
and protease, the two enzymes of paramount importance to the life cycle of the HIV.
Inhibitory effects on hepatitis B and herpes simplex virus type I have also been reported.
The anti-viral effects of mushrooms do not seem to be related to viral adsorption or
81
virucidal effects (i.e. they do not kill the virus), however a number of studies have reported
inhibitory effects at the initial stage of virus replication.
10. Effects on Carcinogenesis

10.1 Bladder Cancer
10.1.1 In vitro studies (human cell lines)
Maitake mushroom D-fraction in combination of interferon (IFN)-alpha has been shown to

potentiate the anticancer activity of IFN-alpha in bladder cancer T24 cells in vitro. The
combination of IFN-alpha 2b (10 000 IU/mL) and Maitake mushroom D-fraction (200
g/mL) reduced growth in T24 cells by ~75% by an induction of G1 arrest with DNAdependent protein kinase activation (Louie et al., 2010). Anti-tumour potential of the
medicinal mushrooms Pleurotus florida and Calocybe indica against T24 bladder cancer
cell lines have also been demonstrated (Selvi et al., 2011).
Cordycepin (3'-deoxyadenosine), from Cordyceps militaris, has been shown to have anti-tumor
effects in two different bladder cancer cell lines, 5637 and T-24 cells. Cordycepin treatment, at
a dose of 200 mM (IC50) during cell-cycle progression resulted in a significant and dosedependent growth inhibition, which was largely due to G2/M-phase arrest (Lee et al., 2009d).
10.2 Breast Cancer

10.2.1 Animal model studies
Extracts from Agaricus bisporous mushrooms have been
suggested as potential breast cancer chemopreventive
agents, as they suppress aromatase activity and estrogen
biosynthesis. A study has evaluated the activity of
mushroom extracts in the estrogen receptorpositive/aromatase-positive MCF-7aro cell line in vitro and
in vivo and found the major active compounds to be
unsaturated fatty acids such as linoleic acid, linolenic acid, and conjugated linoleic acid.
The interaction of linoleic acid and conjugated linoleic acid with aromatase mutants
82
expressed in Chinese hamster ovary cells showed that these fatty acids inhibited
aromatase with similar potency and that mutations at the active site regions affect its
interaction with these two fatty acids. Whereas these results suggest that these two
compounds bind to the active site of aromatase, the inhibition kinetic analysis indicated
that they are non-competitive inhibitors with respect to androstenedione. As only
conjugated linoleic acid was found to inhibit the testosterone-dependent proliferation of
MCF-7aro cells, the physiologically relevant aromatase inhibitors in mushrooms are most
likely conjugated linoleic acid and its derivatives. The in vivo action of mushroom
chemicals was shown using nude mice injected with MCF-7aro cells. The studies showed
that the mushroom extract decreased both tumor cell proliferation and tumour weight with
no effect on the rate of apoptosis (Chen et al., 2006).
A study of the effects of Ganoderma lucidum (Basidiomycetes) polysaccharide (GL-PS)
extract on tumor volume and T(CD4+/CD8+) ratio of tumour infiltrating lymphocytes (TILs)
in breast cancer bearing mice has indicated that GL-PS (100mg/kg/day) could effectively
increase the delayed type hypersensitivity response against sRBC in BALB/c mice.
Furthermore, intraperitoneal injection of this extract in breast cancer bearing mice could
increase T-cell infiltration into the tumour, suggesting a potent immunomodulatory effect
(Mojadadi et al., 2006).

Estrogen is a major factor in the development of breast cancer and in situ estrogen
production by aromatase/estrogen synthetase in breast cancer plays a significant role in
tumour proliferation. An aqueous extract of Agaricus bisporus has been shown to
suppress aromatase activity in a dose-dependent manner. In situ aromatase activity and
cell proliferation were measured using MCF-7aro, an aromatase-transfected breast cancer
cell line. Phytochemicals in the mushroom aqueous extract inhibited aromatase activity
and proliferation of MCF-7aro cells. These results suggest that diets high in mushrooms
may modulate the aromatase activity and function in chemoprevention in postmenopausal women by reducing the in situ production of estrogen (Grube et al., 2001).
Aqueous extracts Maitake (Grifola frondosa), Crimini (Agaricus bisporus), Portabella
(Agaricus bisporus), Oyster (Pleurotus ostreatus) and White Button (Agaricus bisporus)
mushrooms significantly reduced cellular proliferation in MCF-7 human breast cancer cells
by up to 33%, with Maitake and Oyster mushrooms being the most effective. Maitake also
83
significantly induced apoptosis and cytotoxicity in these human breast cancer cells (Martin
and Brophy, 2010) with the activation of apoptosis possibly being mediated via BAK-1
gene activation (Soares et al., 2011). Another study in MCF-7 breast cancer cells has
shown that Coprinus comatus (OFMull.: Fr.) Pers. (Agaricomycetideae), also called the
Shaggy Inc Cap Medicinal Mushroom, contains potent compounds capable of inhibiting
NF-kappa B function that may also act as an antitumor agent (Asatiani et al., 2011).
Screening of 38 species of edible mushrooms on human estrogen-receptor positive (ER+)
(MCF-7) and estrogen-receptor negative (ER-) (MDA-MB-231, BT-20) breast cancer cells
showed that water-based extracts of three mushroom species, Coprinellus sp., Coprinus
comatus, Flammulina velutipes (CME, CCE and FVE, respectively), have anti-tumour
activities including marked growth inhibition of both ER+ and ER- breast cancer cells,
induction of rapid apoptosis (cell death) on both ER+ and ER- cells, and significant
inhibition of MCF-7 tumour colony formation in vitro. The anti-proliferative and cytotoxic
activities of the three mushroom extracts were dose-dependent, regardless of the
hormone receptor status of the cancer cells. The degree of produced cytotoxicity on ERbreast cancer cells was very high. Mushroom extracts CME and FVE induced a rapid
(within 5 hours) apoptosis on MCF-7 and MDA-MB-231 cells. MCF-7 tumour colony
formation rate was reduced by 60% in CCE- and CME-treated cells and nearly completely
inhibited (99%) by FVE treatment. These results suggest that the mushroom species
Coprinus comatus, Coprinellus sp. and Flammulina velutipes contain potent anti-tumour
compounds for breast cancer (Gu and Leonard, 2006). The cultivated mycelium of
Cordyceps sinensis (Cs), has also been shown to have a significant and dose-dependent
inhibitory effect on the proliferation of MCF-7 breast cancer cells (Wu et al., 2007b).
Ganoderma lucidum (Reishi) selectively inhibits cancer cell viability in inflammatory breast
cancer although it does not affect the viability of noncancerous mammary epithelial cells.
Reishi has been shown to inhibit cell invasion and disrupt the cell spheroids that are
characteristic of inflammatory breast cancer. Reishi decreased the expression of genes
involved in cancer cell survival, proliferation, invasion and metastasis, whereas it
increases the expression of IL8 (Martinez-Montemayor et al., 2011).
An array of low molecular weight compounds (including phenolic acids, flavonoids,
tocopherols, carotenoids, sugars and fatty acids) from wild mushrooms have been used in
molecular docking experiments against three known protein targets involved in breast
cancer (aromatase, estrone sulfatase and 17beta-HSD-1) using docking software. The
estimated inhibition constants for the low molecular weight compounds, and the potential
84
structure-activity relationships for the compounds were determined. The compounds 4-Ocaffeoylquinic, naringin and lycopene were the top-ranked potential inhibitors for
aromatase, estrone sulfatase and 17beta-HSD1 which are protein targets in breast cancer
(Froufe et al., 2011, Froufe et al., 2012).
Ganodermanontriol (GDNT), a Ganoderma alcohol is able to suppress proliferation
(anchorage-dependent growth) and colony formation (anchorage-independent growth) of
human breast cancer cells MDA-MB-231. GDNT suppressed expression of the cell cycle
regulatory protein CDC20, which is over-expressed in pre-cancerous and breast cancer
cells compared to normal mammary epithelial cells, and also over-expressed in tumors
when compared to the tissue surrounding the tumor in specimens from breast cancer
patients. GDNT also inhibited invasive behavior (cell adhesion, cell migration, and cell
invasion) through the suppression of secretion of urokinase-plasminogen activator (uPA)
and inhibited expression of uPA receptor (Jiang et al., 2011a).
Ganoderic acid DM (GADM), a triterpenoid isolated from Ganoderma lucidum, inhibits cell
proliferation and colony formation in MCF-7 human breast cancer cells. The mechanisms
involved G1 cell cycle arrest, and apoptosis induced by GADM may be partially due to
GADM-induced DNA damage of the breat cancer cells (Wu et al., 2012).
Antrodia camphorata has been shown to promote cell cycle arrest and apoptosis of
human estrogen-nonresponsive MDA-MB-231 cells and to markedly inhibited the
invasion/migration of highly metastatic MDA-MB-231 human breast cancer cells. A.
camphorata suppressed the phosphorylation of ERK1/2, p38, and JNK1/2, and inhibited
NF-kappaB binding and activation in a dose-dependent manner. These data suggest that
the anti-metastatic activities of Antrodia camphorata against human breast cancer cells
are mediated through suppression of the MAPK signaling pathway (Yang et al., 2011).
Ganoderma lucidum suppresses the invasive behaviour of breast cancer cells by inhibiting
the transcription factor NF-kappaB. It has been shown that Ganoderma lucidum inhibits
proliferation of breast cancer MDA-MB-231 cells by downregulating Akt/NF-kappaB
signaling. Ganoderma lucidum has been shown to suppress phosphorylation of Akt on
Ser473 and downregulate the expression of Akt, which results in the inhibition of NFkappaB activity in MDA-MB-231 cells. The biological effect of Ganoderma lucidum was
demonstrated by cell cycle arrest at G0/G1, which was the result of the downregulation of
expression of NF-kappaB-regulated cyclin D1, followed by the inhibition of cdk4. These
results suggest that Ganoderma lucidum inhibits the growth of MDA-MB-231 breast
85
cancer cells by modulating Akt/NF-kappaB signaling and could have potential therapeutic
use for the treatment of breast cancer (Jiang et al., 2004a).
A subsequent study by the same group on the proliferation of human estrogen-dependent
(MCF-7) and estrogen-independent (MDA-MB-231) breast cancer cells has reported that
G. lucidum inhibits proliferation of human breast cancer cells and contains biologically
active compounds with specificity against the estrogen receptor and NF-kappaB
(transcription factor) signalling (Jiang et al., 2006). More recently, the same group
reported the effects of the structurally related lanostane-type triterpenes, ganoderic acid
A, F and H from Ganoderma lucidum on highly invasive human breast cancer cells. The
activity of ganoderic acids is linked to the hydroxylation in the triterpene lanostane
structure. Hydroxylated triterpenes from G. lucidum could be promising natural agents for
further study of invasive breast cancers (Jiang et al., 2008).
An aqueous extract of Cordyceps militaris (AECM) has been shown to induce apoptosis
via the inhibition of Akt activation in a time-dependent manner. The data suggested that
the apoptopic effect may relate to the activation of caspase-3 and mitochondria
dysfunctions that correlate with the inactivation of Akt (Jin et al., 2008).
The effect of G. lucidum on oxidative stress-induced metastatic behaviour of poorlyinvasive MCF-7 breast cancer cells has also been studied and it has been shown that G.
lucidum inhibited oxidative stress-induced migration of MCF-7 cells by the downregulation of mitogen activated protein kinase (MAPK) signalling, which is involved in
hormonal signalling cascades. G. lucidum suppressed oxidative stress stimulated
phosphorylation of extracellular signal-regulated protein kinases (Erk1/2), which resulted
in the down-regulation of expression of c-fos, and in the inhibition of transcription factors
AP-1 and NF-kappaB. The biological effect of G. lucidum on cell migration was mediated
by the suppression of secretion of interleukin-8 from MCF-7 cells exposed to oxidative
stress. These results suggest that G. lucidum inhibited the oxidative stress-induced
invasive behaviour of breast cancer cells by modulating Erk1/2 signaling and could
possibly be considered as an antioxidant in adjuvant cancer therapy (Thyagarajan et al.,
2006).
A further study by the same group has also shown that an extract from green tea (GTE)
increased the anti-cancer effect of G. lucidum extract (GLE) on cell proliferation
(anchorage-dependent growth) as well as colony formation (anchorage-independent
86
growth) of breast cancer cells. The effect was mediated by the down-regulation of
expression of the oncogene c-myc in MDA-MB-231 cells. (Thyagarajan et al., 2007).
While Ganoderma lucidum has shown significant inhibitory effects on NF- kappa B activity
in breast cancer cells, other mushrooms which have also been reported to produce
biologically active substances and have demonstrated in vitro and in vivo breast cancer
inhibitory activity are Agaricus bisporus, A. brasiliemis, Trametes versicolor, Grifola
frondosa, Inonotus obliquus, Lentinus edodes, Leucoagaricus americanus, Pleurotus
ostreatus and Sparassis crispa (Petrova et al., 2005). Phellinus linteus has also been
shown to suppress growth, angiogenesis and invasive behaviour of breast cancer cells
(Sliva et al., 2008). An apoptopic effect in the human breast cancer cell line ZR-75-30 of a
polysaccharopeptide from Coriolus versicolor has also been reported (Wan et al., 2008).
An alcohol extract from the spore of Ganoderma lucidum has been shown to inhibit the in
vitro proliferation of human umbilical vein endothelial cells and MDA-MB-231 human
breast cancer cells. Further fractionation of the alcohol extract revealed that the ethyl
acetate fraction inhibited both cell lines in a dose-dependent manner from 2 to 40mg/ml
(Lu et al., 2004).
An ethyl acetate fraction from Shiitake (Lentinus edodes) mushrooms has been
investigated using two human breast carcinoma cell lines (MDA-MB-453 and MCF-7), one
human non-malignant breast epithelial cell line (MCF-10F), and two myeloma cell lines
(RPMI-8226 and IM-9). Concentration-dependent anti-proliferative effects of the fraction
were observed in all cell lines. Approximately 50mg/L of the fraction induced apoptosis in
50% of the population of four human tumour cell lines and the fraction-induced apoptosis
may have been mediated through the pro-apoptotic bax protein which was up-regulated.
Cell cycle analysis revealed that the fraction induced cell cycle arrest by significant
decrease of the S phase, which was associated with the induction of cdk inhibitors (p21)
and the suppression of cdk4 and cyclin D1 activity. Compared to malignant tumour cells,
non-malignant cells were less sensitive to the fraction for the suppression of cell growth
and regulation of bax, p21, cyclin D1, and cdk4 expression. A 51% anti-proliferative effect
occurred at the highest concentration of the fraction (800mg/L). The data suggest that
inhibition of growth in tumour cells by the Shiitake mushroom extract may result from an
induction of apoptosis (Fang et al., 2006).
Extracts from Lentinula edodes (Shiitake) have been widely reported to have anti-tumour
activity. However, this activity has been shown to be host-mediated and not by direct
87
cytotoxic activity to cancer cells. A study (Israilides et al., 2008) has demonstrated
cytotoxic and cell growth inhibitory (cytostatic) effects of aqueous extracts of the
mushroom on the MCF-7 human breast adenocarcinoma cell line. The effect was
demonstrated with fruit body and mycelial extracts, the difference being that there was no
significant suppression on normal cells with the latter. Furthermore, mycelial extracts did
not induce any cytostatic effect in both cancer and normal cell lines based on a DNA
synthesis assay. The significant suppression of the proliferation of cancer cells was
reflected by the comparatively low IC50 values and the simultaneous higher respective
values on normal fibroblast cells. In addition to the direct inhibition of the proliferation of
human breast cancer cells in vitro, the Lentinula edodes extract had immuno-stimulatory
properties in terms of mitogenic and co-mitogenic activity in vitro.
Pleurotus ostreatus (Oyster mushroom) has been shown to suppress proliferation of
breast cancer (MCF-7, MDA-MB-231) and colon cancer (HT-29, HCT-116) cells, without
affecting proliferation of epithelial mammary MCF-10A and normal colon FHC cells. Flow
cytometry revealed that the inhibition of cell proliferation by P.ostreatus was associated
with the cell cycle arrest at G0/G1 phase in MCF-7 and HT-29 cells. P.ostreatus also
induced expression of the tumour suppressor p53 and cyclin-dependent kinase inhibitor
p21(CIP1/WAF1). It appears that P. ostreatus suppresses the proliferation of breast and
colon cancer cells via a p53-dependent as well as a p53-independent pathway (Jedinak
and Sliva, 2008).
Hispolon extracted from Phellinus linteus has also been shown to have antiproliferative
effects in breast and bladder cancer cells (Lu et al., 2009).
10.3 Cervical, Ovarian, Endometrial Cancer

Protein extracts of Lentinus edodes C91-3 fermentation broth
administered to mice with cervical cancer prolonged the lifespan
of tumour-bearing mice significantly and killed cervical cancer
U14 cells in vitro (Liu et al., 2009).
88

Polysaccharides from the Lingzhi (Ganoderma Lucidum) have been shown to decrease
CyclinB1 mRNA expression in cervical cancer CaSki cells and inhibit CaSki and HeLa
cell proliferation (Chen et al., 2010d). Ganoderma lucidum has also been shown to inhibit
cell growth and disruption of cell cycle progression via down regulation of cyclin D1 in the
ovarian cancer cell line OVCAR-3. Chemopreventive activities were demonstrated by
suppression of oxidative stress via the induction of antioxidant SOD and catalase as well
as the phase II detoxification enzyme NAD(P)H:quinone oxidoreductase 1 (NQO1) and
glutathione S-transferase PI (GSTP1) via the Nrf2 mediated signaling pathway known to
provide chemoprotection against carcinogenicity (Hsieh and Wu, 2011).
Ethanol and hot water extracts of Pleurotus ferulae have been shown to have antitumourigenic properties in human cervical cancer cell lines and in human lung cancer cell
lines. When A549, SiHa and HeLa cells were incubated with different concentrations of
ethanol and hot water extracts, the ethanol extracts showed strong cytotoxicity against
A549 cells at concentrations over 10mg/mL and against SiHa and HeLa cells at over
40mg/mL (Choi et al., 2004a). Ganoderma lucidum (Lingzhi) polysaccharides have also
been shown to have an inhibitory effect on cervical cancer cells (CA Ski and HeLa cells)
(Chen et al., 2010d).
An anti-proliferative effect of clitocine from the mushroom Leucopaxillus giganteus on
human cervical cancer HeLa cells has also ben reported. The anti-proliferative effect was
via an induction of apoptosis (Ren et al., 2008a). An anti-proliferative effect of ethanol and
water extracts of Pleurotus tuberregium against HeLa cervical cancer cells has also
recently been reported (Maness et al., 2011).
89
10.4 Colon / Colorectal Cancer

10.4.1 Animal model (mouse) studies
Treatment of mice with Pleurotus ostreatus at 100 and 500
mg/kg has suggested that P. ostreatus may prevent
inflammation-associated colon carcinogenesis induced by 2amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and
promoted by dextran sodium sulfate (DSS), via combined
modulatory mechanisms of inflammation and tumor growth via
suppression of COX-2, F4/80, Ki-67 and cyclin D1 expression
in mice. However, incidence of colon tumors and high grade
dysplasia was reduced by 50 and 63% only in the 500 mg/kg
dose (Jedinak et al., 2010). A further study by the same group also showed that the antiinflammatory activity of Pleurotus ostreatus is mediated through the inhibition of NFkappaB and AP-1 signaling (Jedinak et al., 2011a). Induction of natural killer (NK) activity,
activation of macrophages, and inhibition of angiogenesis have all been reported to be
involved in the mechanisms affecting colon cancer cells and reduction of tumor size in
mice (Kim et al., 2011b).
Dietary administration of the fruiting body extract or mycelia extract of the edible
mushroom Pleurotus pulmonarius to mice reduced the formation of aberrant crypt foci,
which precedes colorectal cancer, and of microadenomas. The treatments significantly
lowered the expression of proliferating cell nuclear antigen and increased the number of
cells undergoing apoptosis in the colon as well as inhibiting the expression of the
proinflammatory cytokine TNF-alpha in colonic tissue. The extracts inhibited colitisassociated colon carcinogenesis induced in mice through the modulation of cell
proliferation, induction of apoptosis, and inhibition of inflammation (Lavi et al., 2011).
There is epidemiological evidence that populations with high faecal beta-glucuronidase
activity have greater risk of colon cancer than populations with low faecal betaglucuronidase. This relationship has been investigated using the mousedimethylhydrazine colon carcinogenesis model and a fraction of Ganoderma lucidum
which is a beta-glucuronidase inhibitor. Mice with low faecal beta-glucuronidase activity
induced by consumption of an ether fraction of G. lucidum had significantly fewer aberrant
crypts after injections of 1,2-dimethylhydrazine (DMH) than mice treated with DMH alone,
90
supporting the hypothesis that the ether fraction of G.lucidum can provide some
protection (in this animal model) against the induction of colon cancer (Kim et al., 1995).
4,7-Dimethoxy-5-methyl-l,3-benzodioxole (SY-1) has been shown to decrease the
proliferation of human colon cancer cells (COLO 205) through G0/G1 cell-cycle arrest and
induction of apoptosis. In contrast, SY-1 treatment did not induce significant changes in
G0/G1 phase cell-cycle regulatory proteins in normal human colonic epithelial cells (FHC).
The findings demonstrated that SY-1 inhibited human colon cancer cell proliferation
through inhibition of cell growth and anchorage-independent colony formation (Lien et al.,
2009).
A 23 kDa polysaccharide isolated from Grifola frondosa, while not affecting the
proliferation of colon-26 cells in vitro, did significantly inhibit tumour growth in BALB/cA
mice inoculated with colon-26 cancer cells, via activation of cell-mediated immunity
(Masuda et al., 2009).
10.4.2 Animal model (rat) studies

Intake of dry powdered Lentinula edodes (Shiitake)
has been reported to have no effect on the relative
incidence of tumours in the colon or small intestine
(duodenum) in azoxymethane-treated SpragueDawley rats. Consumption of 1% Shiitake
stimulated growth of invasive adenocarcinomas in
the mid colon and favoured a non-significant
increase in median frequency of aberrant crypt foci in this same region. In contrast,
Shiitake at 4% intake elicited a reduction in colon tumour multiplicity. The authors
suggested a stimulatory action of 1% Shiitake on rat colon tumourigenesis which is
puzzling as the data were not statistically significant. However, the inhibitory actions of 4%
Shiitake mushroom on the indices of rat colon tumourigenesis were statistically validated
(Frank et al., 2006).
The effect of pleuran (beta-1,3-D-glucan isolated from the Oyster mushroom Pleurotus
ostreatus) on the antioxidant status of the organism and on the development of
precancerous aberrant crypt foci (ACF) lesions in the colon have been studied in the male
Wistar rat. A diet containing either 10% pleuran or 10% cellulose was compared with a
91
cellulose-free diet and both were found to significantly reduce conjugated diene content in
erythrocytes and in liver. Particularly significant was the reduction of conjugated dienes in
the colon following pleuran administration. ACF lesions developed in the colon of all
animals fed a cellulose-free diet; however, the incidence was reduced to 64% and 60%
following the cellulose and pleuran diets, respectively. The highest average count of the
most frequent small ACF lesions, and highest total count, was seen in animals fed a
cellulose-free diet. Although ACF lesions were reduced by the cellulose diet, the more
significant reduction statistically (>50%) was achieved with the pleuran diet (Bobek and
Galbavy, 2001).
Chemopreventive and immunomodulatory potential of methanolic (MET) and
dichloromethanic (DCl) extracts of Agaricus blazei were investigated in the postinitiation
stage of colon carcinogenesis in male Wistar rats. Administration of DCl extracts did not
suppress 1,2-dimethylhydrazine-induced colonic aberrant crypt foci nor did it affect the
crypt multiplicity, but the highest dose of MET significantly reduced the development of
preneoplastic lesions in the colon and liver. Lymphoproliferative response was slightly
decreased in the initiated control group, which was restored by treatment with MET. No
toxicity from DCl and MET extracts was observed (Ribeiro-Santos et al., 2008).
The potential blocking effect of Agaricus blazei (Ab) intake on the initiation stage of colon
carcinogenesis has been investigated in a short-term (4-week) bioassay using aberrant
crypt foci (ACF) as a biomarker in male Wistar rats. All 1,2-dimethylhydrazine (DMH)treated rats developed ACF mainly in the middle and distal colon. Agaricus blazei intake
at 5% did not alter the number of ACF induced by DMH or the proliferating cell nuclear
antigen indices in the colonic mucosa. The results did not confirm a chemopreventive
activity of Ab on the initiation stage of rat colon carcinogenesis (Ziliotto et al. 2008)
(Ziliotto et al. 2009).(Ziliotto et al., 2008, Ziliotto et al., 2009).

Ganodermanontriol, a lanostanoid triterpene from Ganoderma lucidum has been shown to
be able to modulate of the beta-catenin pathway, which is involved in the progression of
colorectal cancer. Ganoderma lucidum inhibited proliferation of HCT-116 and HT-29 colon
cancer cells without a significant effect on cell viability, while ganodermanontriol inhibited
transcriptional activity of beta-catenin and protein expression of its target gene cyclin D1
in a dose-dependent manner. A marked inhibitory effect was also seen on Cdk-4 and
92
PCNA expression, whereas expression of Cdk-2, p21 and cyclin E were not affected.
Ganodermanontriol also caused a dose-dependent increase in protein expression of Ecadherin and beta-catenin in HT-29 cells, and suppressed tumor growth in a xenograft
model of human colon adenocarcinoma cells HT-29 implanted in nude mice without any
side-effects and inhibited expression of cyclin D1 in tumors (Jedinak et al., 2011b). In HT29 human colon cancer cells, triterpenes from Ganoderma lucidum have also been shown
to induce programmed cell death (Type II-autophagy) via a mechanism involving inhibition
of p38 mitogen-activated kinase (p38 F) (Thyagarajan et al., 2010). A polysaccharide
extract of Ganoderma lucidum has also been shown to inhibit DNA synthesis in SW 480
human colorectal cancer cells and reduce the formation of DPPH radicals indicating that
G. lucidum extracts inhibit proliferation of human colorectal cancer cells and possesses
antioxidant activity (Xie et al., 2006).
Ganoderic acid T (GA-T) of Ganoderma lucidum inhibited proliferation of HCT-116 cells, a
human colon carcinoma cell line. Cell aggregation and adhesion assays showed that GAT promoted homotypic aggregation and simultaneously inhibited the adhesion of HCT-116
cells to the extracellular matrix (ECM) in a dose-dependent manner (Chen et al., 2010c).
Wound healing assays indicated that GA-T also inhibited the migration of HCT-116 cells in
a dose-dependent manner, and suppressed the migration of 95-D cells, a highly
metastatic human lung tumor cell line, in a dose- and time-dependent manner. In addition,
GA-T inhibited the nuclear translocation of nuclear factor-kappa B (NF-kappa B) and the
degradation of inhibitor of kappa B-alpha (I kappa B alpha), which leads to downregulated expression of matrix metalloproteinase-9 (MMP-9), inducible nitric oxide
synthase (iNOS), and urokinase-type plasminogen activator (uPA). Animal and Lewis
Lung Carcinoma (LLC) model experiments demonstrated that GA-T suppressed tumor
growth and LLC metastasis and down-regulates MMP-2 and MMP-9 mRNA expression in
vivo. These results indicate that GA-T effectively inhibits cancer cell invasion in vitro and
metastasis in vivo (Chen et al., 2010c). An anti-proliferative effect of ethanol and water
extracts of Pleurotus tuberregium against HCT-116 colon cancer cells has also recently
been reported (Maness et al., 2011).
An extract from Ganoderma lucidum has been reported to have apoptotic and antiinflammatory functions in HT-29 human colonic carcinoma cells. Ling Zhi extract (LZE) is
a herbal mushroom preparation that has been shown to induce apoptosis, antiinflammatory action and differential cytokine expression during induced inflammation in
the human colonic carcinoma cell line, HT-29. The extract caused no cytotoxicity in HT-29
cells at doses less than 10,000g/ml. Increasing concentrations reduced prostaglandin E2
93
production, but increased nitric oxide production. LZE treatment induced apoptosis by
increasing the activity of caspase-3. LZE at a concentration of 5,000g/ml decreased the
expression of cyclooxygenase-2 mRNA. Among 42 cytokines tested by protein array in
this study, supplementation of LZE at doses of 500 and 5,000 g/ml to HT-29 cells
reduced the expression of interleukin-8, macrophage inflammatory protein 1-delta,
vascular epithelial growth factor, and platelet-derived growth factor. These results suggest
that LZE has pro-apoptotic and anti-inflammatory functions, as well as inhibitory effects on
cytokine expression during early inflammation in colonic carcinoma cells (Hong et al.,
2004). Similar anti-proliferative and pro-apoptotic activities of fractions of Pleurotus
ostreatus have been reported in HT-29 colon cancer cells in vitro (Lavi et al., 2006).
The effects of an extract of Agaricus blazei Murrill (ABM) has been evaluated on HT-29
human colon cancer cells in severe combined immunodeficiency (SCID) mice. Oral
administration of ABM (up to 45 mg ABM daily for 6 weeks) did not prevent tumor growth,
but compared with the control group (0 mg ABM), the tumor mass appeared to grow more
slowly following ABM doses of 4.5 and 45 mg) (Wu et al., 2011b).
Phellinus linteus has been reported to inhibit tumor growth, invasion, and angiogenesis via
the inhibition of Wnt/beta-catenin signaling in SW480 human colon cancer cells (Song et
al., 2011).
An Agaricus bisporus lectin (ABL) has been shown to inhibit incorporation of [3H]thymidine into DNA of HT29 colon cancer cells by 87%, Caco-2 colon cancer cells by
16%, MCF-7 breast cancer cells by 50%, and Rama-27 rat mammary fibroblasts by 55%
when the cells were grown for 24h in serum-free medium. Similar inhibition of proliferation
of HT29 cells by ABL was found. ABL caused no cytotoxicity to HT29, MCF-7, and Rama27 cells, and inhibition of proliferation in HT29 cells was reversible after removal of the
lectin (Yu et al., 1993).
The reversibility of the anti-proliferative effect of Agaricus bisporus lectin was associated
with its release from cancer cells after internalization. The internalization and subsequent
slow release, with little degradation of the lectin, reflects the tendency of lectins to resist
biodegradation and implies that other endogenous or exogenous lectins may be
processed in this way by intestinal epithelial cells (Yu et al., 2000).
Similar effects in the same cell line (HT-29 human colon cancer cells) have been reported
for an aqueous extract of Inonotus obliquus. The extract inhibited cell growth in a dose-
94
dependent manner, and this inhibition was accompanied by apoptotic cell death. In
addition, the apoptotic cell percentage was closely associated with down-regulation of Bcl2 and up-regulation of Bax and caspase-3. The results suggest that the extract would be
useful as an antitumor agent via the induction of apoptosis and inhibition of the growth of
cancer cells through up-regulation of the expression of proapoptotic proteins and downregulation of antiapoptotic proteins (Lee et al., 2009c).
Ergosterol peroxide from mushrooms has been shown to suppress inflammatory
responses in RAW264.7 macrophages and the growth of HT29 human colon
adenocarcinoma cells. Ergosterol peroxide appeared to suppress cell growth and STAT1
mediated inflammatory responses by altering the redox state in HT29 cells (Kobori et al.,
2007).
A study on the action of lentinan (extracted from Shiitake mushrooms (Lentinus edodes)
has been conducted using murine lymphoma (K36) cells in a AKR mouse model. Further
investigation on the effectiveness of the extracted lentinan was then performed using
human colon-carcinoma cell lines in mice. Six established human colon-carcinoma cell
lines segregated into three groups of different degrees of differentiation were used in this
study. One group was not fed (control) and the second group was prefed with lentinan for
7 days prior to inoculations with the cancer cells. The size of the tumours that developed
was rated after 1 month. Significant regression in tumour formation was observed in
prefed mice compared to control (unfed) mice when K36 or human colon-carcinoma cells
were used. Significant reductions in the size of the tumours were observed in mice prefed
with lentinan. Follow-up investigation proceeded with the use of nude mice (athymic).
Lymphocytes extracted from AKR mice prefed with lentinan for 7 days were inoculated
into the nude mice. This was followed by inoculation of the human colon-carcinoma cell
lines into these mice. Much smaller tumours were formed in nude mice inoculated with
lymphocytes, in contrast to the larger tumours formed in nude mice without lymphocyte
inoculation. The study concluded that the anti-tumour property of lentinan was maintained
with oral administration. In addition, "primed" lymphocytes, when given passively to
immuno-deficient mice, were able to retard the development of tumours in these mice (Ng
and Yap, 2002).
Splenic-sympathetic nerve activity (SNA) was suppressed by an intraduodenal Lentinus
edodes injection in urethane-anesthetized rats, which significantly inhibited increases in
the tumour volume of human colon and breast cancer cells implanted in athymic nude
mice. The findings suggested that Lentinus edodes has an inhibitory effect on tumour
95
proliferation, possibly via a reduction in NK cytotoxicity through the suppression of splenicSNA (Shen et al., 2009).
10.5 Gastric Cancer

The effects of natural polysaccharides isolated from
Phellinus gilvus (PG) in vitro and in vivo against
gastric cancer have been evaluated. PG decreased
cell proliferation and increased cell apoptosis in a
dose-dependent manner in vitro and also led to a
marked inhibition of tumour growth and significant
decrease in the incidence of peritoneal
carcinomatosis. Histological analysis of the tumour confirmed a significant increase in
tumour cell apoptosis by PG, indicating reduced tumour cell proliferation. The data
showed that polysaccharides isolated from PG significantly inhibited tumour growth and
metastasis in an orthotopic model of human gastric adenocarcinoma, without detectable
adverse effects (Bae et al., 2006).
Toth and co-workers have recently reported the inhibition of intestinal cancer by a hot
water extract of the Coriolus versicolor (Turkey Tail) mushroom in C57bl/6j-Apc(Min) mice
(Toth et al., 2007).

The induction of apoptosis by extracts of Ganoderma lucidum has previously been
reported, however, more recent data have proposed that the mechanisms involved (at
least in human gastric carcinoma cells) involve caspase pathways which are associated
with inactivation of the Akt signalling pathway (Jang et al., 2010b).
Recombinant Lz-8 (rLz-8), a protein from Ganoderma lucidum induced endoplasmic
reticulum stress-mediated autophagic cell death in the human gastric cancer cell line
SGC-7901, but caspase inhibitors did not prevent rLz-8-induced cell death, and therefore
96
the autophagic response induced by rLz-8 is independent of caspase activation (Liang et

al., 2012).
Induction of apoptosis in human gastric epithelial AGS cancer cells by an aqueous extract
of Agaricus blazei has been demonstrated. It was found that an Agaricus blazei extract
could inhibit cell growth in a dose-dependent manner, which was associated with the
arrest of G2/M phase and the induction of apoptotic cell death via caspase-3 activation
(Jin et al., 2006).
An exopolysaccharide produced from the medicinal mushroom Fomes fomentarius, has
been reported to have a direct anti-proliferative effect in vitro on SGC-7901 human gastric
cancer cells in a dose- and time-dependent manner (Chen et al., 2008).
A water-soluble extract of Grifola frondosa has been shown to inhibit the proliferation of
four human gastric cancer cell lines (TMK-1, MKN28, MKN45 and MKN74) in a timedependent manner. The inhibition was most pronounced in TMK-1 cells, which exhibited
up to 90% inhibition after treatment with 10% extract for 3 days. Induction of apoptosis
was confirmed by fluorescence-activated cell sorting analyses, while Western blot
analyses of TMK-1 cells after treatment with the extract revealed increases in
intracytoplasmic cytochrome c and cleavage of caspase-3 and poly(ADP-ribose)
polymerase, but no expression of p21 or Bax. The caspase-3 protease activities in lysates
of TMK-1 cells treated with 1% or 10% of the extract were approximately 3-fold higher
than in control cells. The data suggest that this extract from Grifola frondosa produces
potential antitumour effects on gastric cancer via an induction of apoptosis of TMK-1 cells
by caspase-3-dependent and -independent pathways (Shomori et al., 2009).
10.6 Leukemia
The effects of a beta-glucan supplement (Lentinan)

from Lentula edodes (Shiitake) on BN rats have been
studied and in a preclinical model of acute myeloid
leukemia. BN rats supplemented daily with lentinan
exhibited weight gains, increased white blood cells,
monocytes and circulating cytotoxic T-cells, and had a
97
reduction in anti-inflammatory cytokines IL-4, IL-10, and IL-6. A combination of lentinan

with standards of care in acute myeloid leukemia, idarubicin, and cytarabine increased
average survival compared with monotherapy and reduced cachexia suggesting that
nutritional supplementation of cancer patients with lentinan would warrant investigation
(McCormack et al., 2010).

A recent study demonstrated that agaritine purified from Agaricus blazei Murrill exerts
anti-tumor activity against leukemic cells in vitro (Endo et al., 2010b). Agaritine inhibited
the proliferation of leukemic cell lines U937, MOLT4, HL60 and K562, but showed no
significant effect on normal lymphatic cells. The data also showed that this activity was
distinct from that of beta-glucan, which indirectly suppresses proliferation of tumor cells.
This conclusion of direct anti-tumor activity by agaritine against leukemic tumor cells in
vitro contrasts to the carcinogenic activity previously ascribed to it in animal studies
carried out around 20-30 years ago. A more recent study by the same group has now
shown that the mechanism by which agaritine may act in U937 leukemic cells is via the
moderate induction of apoptosis via caspase activation through cytochrome C release
from mitochondria (Akiyama et al., 2011). Induction of apoptosis and alterations in signal
transduction kinases (Akt and Erk) are also produced by active fractions from Ganoderma
lucidum on human leukemia cells (Calvino et al., 2010). Hericium erinaceus
(Yamabushitake) mushroom-induced apoptosis of U937 human monocytic leukemia cell
has been reported to be via an effect on cell proliferation that involves activation of
mitochondria-mediated caspase-3 and caspase-9 but not caspase-8 (Sung Phil et al.,
2011). Extracts from Agaricus bisporus and Phellinus linteus have also been shown to
induce proapoptotic effects in the human leukemia cell line K562 (Shnyreva et al., 2010).
Extracts from Agaricus bisporus (Jagadish et al., 2009), Agaricus blazei (Gao et al., 2007),
Hypsizigus marmoreus (Mizumoto et al., 2008) and other mushrooms have been shown to
inhibit cell proliferation of HL-60 leukemia cells and other leukemia human cell lines via the
induction of apoptosis. Mechanisms by which apoptosis is induced include down-regulation of
telomerase activity and up-regulation of mRNA expression of the caspase-3 gene (Gao et al.,
2007), regulation of Bcl-2 and caspase-3 (Jin et al., 2007), cleavage of poly (ADP-ribose)
polymerase and pro-caspase 3 (Bae et al., 2009), mitochondrial membrane potential loss and
caspase activation (Mizumoto et al., 2008), release of mitochondrial cytochrome c and
subsequent activation of caspase-9 and caspase-3 (Hsu et al., 2008b) and via the signal
98
transduction kinases Akt and Erk (Calvino et al., 2010). These extracts appear to exert tumorselective cytotoxicity, with studies reporting no significant cytotoxic effects on normal cell lines
(Lau et al., 2004).
A nonlectin glycoprotein (PCP-3A) isolated from the fruiting body of the edible golden
oyster mushroom Pleurotus citrinopileatus has been shown to stimulate human
mononuclear cells to secrete cytokines TNF-alpha, IL-2, and IFN-gamma, which
subsequently inhibited the growth of U937 human myeloid leukemic cells (Chen et al.,
2010a).
Kinase inhibitors have been used for the treatment of chronic myeloid leukemia (CML) in
humans. Despite high rates of clinical response, CML patients can develop resistance to
these kinase inhibitors mainly due to point mutations within the Abl kinase domain of the
fusion protein. A crude extract of the mushroom Daedalea gibbosa has been reported to
inhibit kinase activity of Bcr-Abl kinase, and the active component has been identified as
oleic acid (Khamaisie et al., 2011).
It is interesting to note that aqueous and aqueous/ethanolic extracts of Hericium erinaceus
(Yamabushitake) mushroom were able to induce apoptosis in U937 human monocytic
leukemia cells, however, acidic and alkaline extracts with similar proximate compositions
were both inactive (Kim et al., 2011a).
10.7 Liver Cancer

In vivo rodent studies have reported hepato-protective
effects on both chemically-induced liver toxicity and
hepato-carcinogenesis by extracts from Agaricus blazei
(Barbisan et al., 2002, Pinheiro et al., 2003) and Pleurotus
pulmonarius (Wasonga et al., 2008).
99

Lucidenic acids (triterpenoids) isolated from Ganoderma lucidum (Weng et al., 2007),
hyperbranched -glucan, extracted from Pleurotus tuberregium (Tao et al., 2006) and extracts
from Cordyceps sinensis (Wu et al., 2007b) and Chaga (Inonotus obliquus) mushrooms (Youn
et al., 2008) have been shown to inhibit the proliferation of HepG2 human hepatocellular
carcinomas. As reported above for human leukemia cell lines, such extracts appear to be have
tumor-selective cytotoxicity, without significant effects on normal human liver cell lines (Lin et
al., 2003).
Hispolon, an active phenolic compound of Phellinus igniarius, induces apoptosis and cell
cycle arrest of human hepatocellular carcinoma Hep3B cells by modulating ERK
phosphorylation. Hispolon inhibited cellular growth of Hep3B cells in a time-dependent
and dose-dependent manner, through the induction of cell cycle arrest at S phase
measured using flow cytometric analysis and apoptotic cell death. Hispolon-induced Sphase arrest was associated with a marked decrease in the protein expression of cyclins
A and E and cyclin-dependent kinase (CDK) 2, with concomitant induction of
p21waf1/Cip1 and p27Kip1. Exposure of Hep3B cells to hispolon resulted in apoptosis as
shown by caspase activation, PARP cleavage, and DNA fragmentation. Hispolon
treatment also activated JNK, p38 MAPK, and ERK expression. Inhibitors of ERK
(PB98095), but not those of JNK (SP600125) and p38 MAPK (SB203580), suppressed
hispolon-induced S-phase arrest and apoptosis in Hep3B cells. These findings establish a
mechanistic link between the MAPK pathway and hispolon-induced cell cycle arrest and
apoptosis in Hep3B cells (Guan-Jhong et al., 2011, Huang et al., 2011). Hispolon has also
been shown to suppress SK-Hep1 human hepatoma cell metastasis by inhibiting matrix
metalloproteinase-2/9 and urokinase-plasminogen activator through the PI3K/Akt and
ERK signaling pathways (Huang et al., 2010b).
A lectin isolated from Agrocybe aegerita has been shown to bind to the surface of
hepatoma cells, leading to induced cell apoptosis in vitro, and to exert an anti-hepatoma
effect in vivo via inhibition of tumor growth and extending the survival time of tumor
bearing mice (Jiang et al., 2012). Mechanistic studies of apoptosis in human
hepatocellular carcinoma cells have shown that Agaricus blazei Murill is able to act as an
enhancer to sensitize doxorubicin (Dox)-mediated apoptotic signaling, and this
sensitization can be achieved by enhancing intracellular Dox accumulation via the
100
inhibition of NFkappaB activity. These findings suggest that Agaricus blazei Murill, when
combined with low doses of Dox, may have the potential to provide more efficient
therapeutic effects against drug-resistant human hepatocellular carcinoma (Lee and
Hong, 2011).
It has recently been demonstrated that polysaccharides from Phellinus linteus (PL) inhibit
proliferation and colony formation of HepG2 and that the growth inhibition of HepG2 cells
was mediated by S-phase cell cycle arrest. Phellinus linteus also markedly inhibited
cancer cell adhesion and invasion of the extracellular matrix and PL-induced apoptosis
was associated with a reduction in B-cell lymphoma 2 levels and an increase in the
release of cytochrome c. The results suggest that PL exerts a direct antitumor effect by
initiating apoptosis and cell cycle blockade in HepG2 cells (Wang et al., 2012a).
10.8 Lung Cancer

An in vivo study in mice with Lewis lung carcinoma treated with
an aqueous extract of Hypsizigus marmoreus showed a
significant increase in life span when given it by intraperitoneal
administration, but not as much by oral administration. The
extract inhibited spontaneous tumor metastasis in mice bearing
the carcinoma and significantly decreased the number of
metastasized nodules (Saitoh et al., 1997).

In vitro studies have shown that three triterpene aldehydes, lucialdehydes A - C, from the
fruiting bodies of Ganoderma lucidum, possess cytotoxicity against murine and human tumor
cells (Lewis lung carcinoma (LLC), T-47D, Sarcoma 180, and Meth-A tumor cell lines) (Gao et
al., 2002), while Phellinus linteus has been shown to mediate cell-cycle arrest at a low
concentration and apoptosis in response to a high dose in mouse and human lung cancer cells
(Guo et al., 2007). Blazein, a steroid isolated from Agaricus blazei Murrill (Himematsutake), has
also been reported to induce cell death and morphological change indicative of apoptotic
chromatin condensation in human lung cancer LU99 and stomach cancer KATO III cells (Itoh et
101
al., 2008), and an extract from Pleurotus ferulae has been reported to have cytotoxic effects on
human lung cancer and cervical cancer cell lines (A549, SiHa and HeLa cells) (Choi et al.,
2004a).
Recombinant Ling Zhi-8 (rLZ-8), an immunomodulatory protein cloned from Ganoderma
lucidum (Reishi or Ling Zhi) inhibits the proliferation of A549 human lung cancer cells. The
antitumor effect was via a modulation of p53 via ribosomal stress. rLZ-8 inhibited lung
cancer cell growth in vitro and also in vivo, in mice transplanted with Lewis lung carcinoma
cells (Wu et al., 2011a).
A recombinant fungal immunomodulatory protein (termed GMI), has been cloned from
Ganoderma microsporum and purified. GMI exhibited an inhibitory effect on epidermal
growth factor-induced migration and invasion in A549 lung cancer cells. GMI inhibited
EGF-induced phosphorylation and activation of EGFR and AKT pathway kinases in a
dose-dependent manner, and EGF-induced activation of Cdc42 GTPase was inhibited by
GMI, while GMI had little effect on the EGF-induced activation of Rac1 GTPase. GMI also
inhibited the EGF-induced microfilament depolymerisation (Lin et al., 2010a).
10.9 Oral Cancer

Ethanol extracts (0.9 mg/ml) and hot water extracts (0.7 mg/ml) of Agaricus brasiliensis
Mural (ABM) caused morphological changes and significantly reduced viability of human
oral cancer CAL 27 Cells after 48 h of treatment. Both extracts were able to induce
apoptotic cell death in CAL 27 cells via the release of cytochrome c from mitochondria into
the cytoplasm and activation of caspase-3 in vitro (Fan et al., 2011).
The responses of human oral squamous cell carcinoma (OSCC) cells to Lentinan, beta-(1
-> 3)-D-glucan, an extract from Lentinus edodes (0.1 mg/kg/day, 2 times/week), alone and
in combination with S-1, an oral antineoplastic agent that can induce apoptosis in various
types of cancer cells (6.9 mg/kg/day, 7 times/week)has been studied using a nude mouse
xenograft model. Combined therapy of Lentinan and S-1 markedly exerted antitumor
effects on human OSCC xenografts and significantly induced apoptotic cells in tumors
treated with Lentinan plus S-1, with no loss of body weight being observed in mice treated
with the combined therapy (Harada et al., 2010).
102
10.10 Ovarian Cancer

Ganoderma lucidum has been shown to significantly decrease ovarian cancer cell
numbers in vitro in a dose-dependent manner. Ganoderma lucidum also inhibited colony
formation, cell migration and spheroid formation. Ganoderma lucidum also induced cell
cycle arrest at the G2/M phase, induced apoptosis by activating caspase 3, increased p53
but inhibited Akt expression (Zhao et al., 2011).
10.11 Prostate Cancer

10.11.1Animal model (mouse) studies
Polysaccharide-K (PSK), an extract of the mushroom
Trametes versicolor, has been shown to enhance docetaxelinduced prostate cancer tumor suppression, apoptosis and
antitumor responses in transgenic adenocarcinomas of
mouse prostate (TRAMP)-C2-bearing mice. Combining PSK
with docetaxel significantly induced higher tumor
suppression than either treatment alone, including a
reduction in tumor proliferation and enhanced apoptosis. Combined PSK and docetaxel
treatment led to a lower decrease in number of white blood cells than docetaxel alone, an
effect accompanied by increased numbers of tumor-infiltrating CD4+ and CD8+ T cells.
PSK with or without docetaxel significantly enhanced mRNA expression of IFN-gamma
compared to control, but did not significantly alter T-regulatory FoxP3 mRNA expression
in tumors (Wenner et al., 2012).
A Phellinus linteus extract has recently been reported to sensitize advanced prostate
cancer cells to apoptosis in athymic nude mice (Tsuji et al., 2010). In this study, a
xenograft assay, together with in vitro assays, were undertaken to evaluate the effect of
Phellinus linteus on the genesis and progression of the tumours formed from the
inoculation of prostate cancer PC3 or DU145 cells. Although Phellinus linteus treatment
did not prevent the formation of the inoculated tumours, the growth rate of the tumors after
Phellinus linteus treatment was significantly attenuated. Apoptosis occurred with the
activation of caspase 3 in the tumours formed by inoculating prostate cancer DU145 or
103
PC3 cells. The data were in agreement with data from cultured cells. The in vivo study
suggested that Phellinus linteus attenuated tumour growth and caused tumour regression
by inducing apoptosis.
10.11.2 Animal model (rat) studies

The inhibitory effects of methanol extracts of 19 edible and medicinal mushrooms on 5alpha-reductase activity have been reported, with an extract of Ganoderma lucidum Fr.
Krast (Ganodermataceae) showing the strongest 5-alpha-reductase inhibitory activity. The
treatment of the fruit body of Ganoderma lucidum, or the extract prepared from it,
significantly inhibited the testosterone-induced growth of the ventral prostate in castrated
rats. The results showed that Ganoderma lucidum might be a useful ingredient for the
treatment of benign prostatic hyperplasia (Fujita et al., 2005).
Prostate weight increased significantly (37%) following treatment with a Phellinus linteus
extract, and in particular, the stromal component of the prostate increased significantly by
80%. A suppression of transforming growth factor-beta1 expression by 56% was observed
with the mushroom extract treatment. It was found that this mushroom extract enlarged
the prostate and therefore administration of Phellinus linteus extract should be considered
carefully by those with an enlarged prostate (Shibata et al., 2005).
Agaricus bisporus mushroom extract and one of its major components, conjugated linoleic
acid (CLA) have been shown to decrease DU145 and PC3 prostate tumour size and
tumour cell proliferation in nude mice treated with the mushroom extract, whereas tumour
cell apoptosis was increased compared to pair-fed controls. Gene network analysis
identified alterations in networks involved in cell death, growth and proliferation, lipid
metabolism, the TCA cycle and immune response (Adams et al., 2008).

Altered androgen receptor (AR) activity caused by point mutations or signalling
mechanisms that regulate AR function has been proposed as a key mechanism in the
transition to the androgen-independent stage of prostate cancer. It has been
demonstrated that a hexane extract prepared from Coprinus comatus ( C. comatus) strain
734 was able to reduce AR levels and prostate-specific antigen gene expression in the
LNCaP-treated cell line (Dotan et al., 2011a). A further study from the same group
104
isolated 2 fractions from the same mushroom strain that inhibited AR-mediated reporter
activity and reduced the levels of AR and prostate-specific antigen (PSA) transcripts in
LNCaP cells. One of these fractions (F-32) also inhibited the proliferation and clonigenicity
of LNCaP cells and inhibited the binding of AR to the PSA enhancer region and inhibited
Akt-mediated AR phosphorylation at Ser 213 (Dotan et al., 2011b). The pharmaceutical
value of the Basidiomycota fungi Coprinus comatus has also been reviewed by the same
group (Dotan et al., 2010).
PSP, an active component extracted from Coriolus versicolor has been reported to be
effective in targeting prostate cancer stem/progenitor cells (CSCs). Treatment of the
prostate cancer cell line PC-3 with PSP led to the down-regulation of CSC markers
(CD133 and CD44) in a time and dose-dependent manner. PSP treatment also inhibited
PC-3 cell tumorigenicity in vivo, indicating that PSP can suppress prostate CSC
properties. Transgenic mice (TgMAP) that spontaneously develop prostate tumors, that
were orally fed with PSP for 20 weeks did not develop tomours, while 100% of the mice
that were fed with water only developed prostate tumors at the end of the 20 weeks,
suggesting that PSP treatment can inhibit prostate tumor formation in these mice (Luk et
al., 2011).
The effects of Agaricus blazei Murill on the growth of human prostate cancer have been
examined in vitro and in vivo. A. blazei, particularly in a broth fraction, inhibited cell
proliferation in both androgen-dependent and androgen-independent prostate cancer cell
lines. The broth of A. blazei induced lactate dehydrogenase leakage in three cancer cell
lines, whereas the activities of caspase 3 and the DNA fragmentation were enhanced the
most in androgen-independent PC3 cells. Oral supplementation with the broth of A. blazei
(with the higher ratio of beta-glucan) significantly suppressed tumour growth without
inducing adverse effects in severe combined immunodeficient mice with PC3 tumor
xenograft. The data suggested that the broth of A. blazei may directly inhibit the growth of
prostate cancer cell via an apoptotic pathway and suppress prostate tumor growth via
antiproliferative and antiangiogenic mechanisms (Yu et al., 2009a).
Beta-glucan, a polysaccharide, of the Grifola frondosa (Maitake) mushroom, has a
cytotoxic effect, presumably through oxidative stress, on human androgen-independent
prostatic cancer PC-3 cells in vitro, leading to apoptosis (Fullerton et al., 2000). Another
study in the same cell line showed similar cytotoxic effects from a water-soluble extract
from Pleurotus ostreatus (Oyster), although the active components were not identified (Gu
and Leonard, 2006).
105
Ganoderma lucidum has also been shown to inhibit proliferation in a dose- and timedependent manner and induce apoptosis in human prostate cancer cells PC-3 (Jiang et
al., 2004b). However, the molecular mechanisms responsible for the inhibitory effects of
G. lucidum on these prostate cancer cells are still unclear. It has been found that G.
lucidum inhibits the early event in angiogenesis, capillary morphogenesis of the human
aortic endothelial cells. These effects are caused by the inhibition of constitutively active
AP-1 in prostate cancer cells, resulting in the down-regulation of secretion of Vascular
Endothelial Growth Factor and Transforming Growth Factor beta (TGF-beta1) from PC-3
cells. The data suggest that G. lucidum inhibits prostate cancer-dependent angiogenesis
by modulating MAPK (mitogen activated protein kinase) and Akt signaling and could have
potential therapeutic use for the treatment of prostate cancer (Stanley et al., 2005).
Interferon (IFN)-alpha2b has also been shown to have synergistic effects with mushroom
extracts in inducing significant reductions reduction in PC-3 cell growth. This appears to
be due to a synergistic potentiation leading to a G1 cell cycle arrest (Pyo et al., 2008).
Polysaccharides and ethanol extracts of the fruiting bodies of Tremella aurantia
mushrooms have also been shown to possess growth-inhibitory activity in LNCaP and
PC-3 human prostate cancer cells (Kiho et al., 2010).
Phellinus linteus has been reported to sensitise apoptosis induced by doxorubicin (an anticancer drug) in prostate cancer LNCaP cells suggesting that Phellinus linteus may have
therapeutic potential to augment the magnitude of apoptosis induced by anti-prostate
cancer drugs (Collins et al., 2006). Putrescine-1,4-dicinnamide from the gilled mushroom
Pholiota spumosa (Basidiomycetes) has also been reported to inhibit cell growth of an
androgen-independent human prostate cancer (PCA) cell line by inducing apoptosis,
mediated, at least in part, by the activation of caspase cascades (Russo et al., 2007).
Ergosterol peroxide derived from edible mushrooms has been shown to exert anti-tumor
activity in several cancer cells. For example, ergosterol peroxide has been shown to
attenuate the growth of prostate cells, at least in part, triggering an apoptotic process in
androgen-insensitive (DU-145) human prostate cancer cells (Russo et al., 2010). In a
recent study in human multiple myeloma U266 cells, ergosterol peroxide exerted
antitumor activity in multiple myeloma U266 cells partly with anti-angiogenic activity
targeting the JAK2/STAT3 signalling pathway (Rhee et al., 2012).
106
10.12 Skin Cancer

Proflamin, isolated from the culture mycelium of Flammulina
velutipes (Curt. ex Fr.) Sing. is a weakly acidic glycoprotein
containing more than 90% protein and less than 10%
carbohydrate, and has a molecular weight of ~13,000 Da.
Proflamin has been shown to be markedly effective against the
syngeneic tumours, B-16 melanoma (B-16) and adenocarcinoma
755 (Ca-755) in the mouse. The increases in median survival time
of treated mice with B-16 and Ca-755 were 86% and 84%,
respectively. Proflamin exhibited no cytocidal effect against the cultured cell lines in vitro.
Oral administration of proflamin produced no lethal or any other apparent adverse effect in
mice (Ikekawa et al., 1985).
An acidic polysaccharide from Phellinus linteus has been shown to markedly inhibit
melanoma cell metastasis in mice, and directly inhibit cancer cell adhesion to, and
invasion through, the extracellular matrix, but it had no direct effect on cancer cell growth.
In addition, the authors reported that PL increased macrophage NO production. These
results suggest that Phellinus linteus has two anti-metastatic functions - it acts as an
immuno-potentiator and as a direct inhibitor of cancer cell adhesion (Han et al., 2006).
An extract of Ganoderma lucidum has also been reported to reduce chemically-induced
mammary adenocarcinomas in Sprague Dawley rats and skin tumours Balb/c mice
(Lakshmi et al., 2009).
Mushroom oligosaccharides that down-regulate production of immuno-suppressive
cytokines by ultraviolet radiation injured keratinocytes appear to be promising agents for
the prevention of environmental (sun induced) skin cancer (Pelley and Strickland, 2000).
10.12.2 In vitro studies (animal cell lines)

Lentinula edodes has been shown to reduce cell proliferation and induce apoptosis in CH72
mouse skin carcinoma cells via an induction of a transient G1 arrest with no effect in non-
107
tumorigenic (C50) cells (Gu and Belury, 2005). Similarly, reduction of cell proliferation of B-16
melanoma cells by arrest in the G0/G1 phase of the cell cycle, followed by both apoptotic and
secondary necrotic cell death has been demonstrated for a methanol extract of Coriolus
versicolor (Harhaji et al., 2008). In contrast, proflamin, isolated from Flammulina velutipes,
exhibited no cytotoxic effects against B-16 melanoma (B-16) and adenocarcinoma 755 (Ca755) cultured cell lines in vitro, but increased the median survival time of mice treated with B-16
and Ca-755 by 86% and 84%, respectively, with no apparent adverse effects (Ikekawa et al.,
1985).
An acidic polysaccharide from Phellinus linteus has been shown to markedly inhibit melanoma
cell metastasis in mice, and directly inhibit cancer cell adhesion to, and invasion through, the
extracellular matrix, with an increase in macrophage NO production but to have no direct effect
on cancer cell growth. These results suggest that Phellinus linteus has two anti-metastatic
functionsit acts as an immunopotentiator and as a direct inhibitor of cancer cell adhesion
(Han et al., 2006).
10.13 DNA Damage

It has been suggested that synthetic agaritine (i.e. not
extracted from mushrooms) is quickly metabolized in
mice and disappears in the plasma, whereas DNA
damage after a single administration of synthetic
agaritine lasts for a longer time (Kondo et al., 2008). The
inference for DNA damage in this study was from a result
of a separate in vitro test. While data with a particular
marker of oxidative stress showed this effect, a similar
experiment with a different marker of oxidative stress did
not, thus the authors made these comments based on their results with one particular
marker only. In contrast, recent research (Endo et al., 2010b) has ascribed anti-tumor
activity of agaritine (from mushrooms) against leukemic cells, and a recent review (Roupas
et al., 2010a) also concluded that agaritine from consumption of cultivated Agaricus
bisporus mushrooms poses no known toxicological risk to healthy humans. Another in vivo
study demonstrated that crude extracts of Agaricus blazei Murrill significantly reduced DNA
108
damage in liver induced by diethylnitrosamine in adult male Wistar rats (Barbisan et al.,
2003), while DNA strand breaking by the carbon-centered radical generated from 4(hydroxymethyl) benzenediazonium salt from Agaricus bisporus has been reported in the
mouse (Hiramoto et al., 1995).
A polysaccharide protein complex (PPC-Pr) isolated from the mushroom Phellinus
rimosus has been shown to have a protective effect (at doses of 5 and 10 mg/kg body
weight intraperitoneally for 5 days consecutively) against oxidative stress induced by
gamma radiation (4 Gy) in Swiss albino mice. PPC-Pr treatment enhanced the declined
levels of antioxidants and demonstrated a DNA protective effect (as determined by a
Comet assay) as well as significantly increasing the survival rate of animals (Joseph et al.,
2012). An earlier study from the same group at the same doses of PPC-Pr had reported
its effect on alleviating gamma radiation-induced toxicity in the Swiss albino mouse model
(Joseph et al., 2011).
10.13.2 In vitro studies

In vitro studies have shown that a heat-labile protein from Agaricus bisporus protects Raji
cells (a human lymphoma cell line) against H2O2-induced oxidative damage to cellular DNA
(Shi et al., 2002). Similar protective effects against H2O2-induced oxidative damage to
cellular DNA have been demonstrated with cold (20C) and hot (100C) water extracts of
Agaricus bisporus and Ganoderma lucidum fruit bodies, respectively. No protective effects
were observed with mushroom derived preparations from Flammulina velutipes, Auricularia
auricula, Hypsizygus marmoreus, Lentinula edodes, Pleurotus sajor-caju, or Volvariella
volvacea (Rocha et al., 2002). Similar reductions in DNA fragmentation (Comet assay),
compared with H2O2 as a positive control, have been reported from Chaga mushroom
(Inonotus obliquus)(Park et al., 2004), while an aqueous extract from Agrocybe cylindracea
strain B has also been shown to protect against DNA damage in HepG2 cells (Wang et al.,
2004). Some edible mushrooms therefore represent a valuable source of biologically active
compounds with potential for protecting cellular DNA from oxidative damage, while other
mushroom varieties do not.
Beta-glucan from Agaricus brasiliensis has been reported to be devoid of mutagenic activity
and to provide a significant dose-dependent protective effect against DNA damage in the
dose range 20-80 mg/ml (Angeli et al., 2006). Furthermore, a possible chemoprotective
effect of -glucan extracted from Agaricus blazei against DNA damage induced by
109
benzo[a]pyrene, using the comet assay (genotoxicity) and micronucleus assay with
cytokinesis block (mutagenicity) in a human hepatoma cell line (HepG2) has suggested that
b-glucan did not exert a genotoxic or mutagenic effect, but that it did protect against DNA
damage via binding to benzo[a]pyrene or by the capture of free radicals produced during its
activation (Angeli et al., 2009).
Strong DNA protective effects from oxidative damage have been reported for protein
extracts from selenium-enriched Ganoderma lucidum (Se-GLPr), and this effect increased
with increasing Se content (Zhao et al., 2004). Polysaccharide extracts from Se-enriched G.
lucidum have also been shown to protect DNA from hydroxyl radical oxidative damage in a
dose dependent manner (Zhao et al., 2008). A water-soluble polysaccharide from
Ganoderma lucidum was protective against hydroxyl radical-induced DNA strand breaks
(Kim and Kim, 1999), and radioprotective properties of an aqueous extract of Ganoderma
lucidum against radiation-induced plasmid pBR322 DNA strand breaks have been
demonstrated that may be due to inhibition of lipid peroxidation (Pillai et al., 2006).
Oral administration of Ganoderma lucidum extract (GLE) to tumor-bearing Swiss albino mice
along with exposure to gamma radiation has been shown to result in tumour regression.
Single-cell gel electrophoresis (comet assay) on cells of normal and tumour tissues from
tumour-bearing animals treated with GLE and radiation, revealed that there was significant
reduction in radiation-induced damage to cellular DNA in normal tissues compared to the
tumour, indicating preferential protection to normal tissues and possible use as an adjuvant
in radiotherapy, for tumour regression and prevention of radiation-induced cellular damage
in normal tissues (Gopakumar et al., 2010).
Supplementation with Agaricus blazei, carried out under pre-treatment, simultaneous
treatment, post-treatment and pre-treatment+continuous conditions, has shown that A.
blazei did not have genotoxic activity but showed antigenotoxic activity (Comet assay).
Supplementation caused an increase in the number of monocytes and in phagocytic activity,
suggesting that supplementation increases a proliferation of monocytes, consequently
increasing phagocytic capacity especially in the groups pre-treatment, simultaneous and
pre-treatment+continuous. The data suggest that A. blazei could promote
immunomodulation which can account for the destruction of cells with DNA alterations that
correlate with the development of cancer, since this mushroom was demonstrated to have a
preventive effect against pre-neoplastic colorectal lesions evaluated by the aberrant crypt
foci assay (Ishii et al., 2011).
110
Polysaccharides isolated from Ganoderma lucidum have been reported to enhance the
repair of radiation induced DNA strand breaks in human cells after 120min of exposure
(Pillai et al., 2010).
10.14 Summary of Anti-Cancer Properties

Anti-tumor effects, primarily in human cell lines, have been reported for polysaccharides
extracted from various mushrooms. The polysaccharides generally belong to the betaglucan family of compounds and appear to exert their anti-tumorigenic effects via
enhancement of cellular immunity. Apoptosis and/or anti-proliferative effects on
carcinomas and cell lines is also a mechanism shared by several mushrooms and their
extracts in studies of anti-cancer effects.
Anti-tumor effects of proteoglycan fractions from a variety of mushrooms, including
Agaricus bisporus, involve the elevation of natural killer (NK) cell numbers and the
stimulation of inducible nitric oxide (NO) synthase gene expression, which is then followed
by NO production in macrophages via activation of the transcription factor, NF-kappaB.
Activation of NK cells is likely via interferon-gamma and interleukin mediated pathways. In
addition to the apoptotic and anti-proliferative effects, the anti-inflammatory and antimicrobial / viral effects described in this report may also contribute to the anti-carcinogenic
effects of mushrooms and their extracts, although such direct links have not been
established to date. While studies in human cell lines provide supporting evidence, welldesigned human clinical trials are required before the anti-cancer mechanisms and health
outcomes in humans can be validated. In recent years, a number of human trials have
been undertaken and these have been described earlier in this report.
111
11. Effects on Cardiovascular Health

A water-soluble polysaccharide extract of Pleurotus
eryngii has been shown to significantly increase the
activitiy of antioxidant enzymes and effectively
remove free radicals in a liver-injury mouse model.
Furthermore, in a high-fat-load mouse model, the
extract decreased total cholesterol, total triglyceride,
and low-density lipoprotein cholesterol, and
increased high-density lipoprotein cholesterol.
Histopathological observations indicated that the
extract could effectively prevent excessive lipid
formation in liver tissue (Chen et al., 2012b).
Supplementation of rats on a high fat diet with Shiitake Mushroom (Lentinus edodes)
powder resulted in negative correlations between the amount of Shiitake mushroom
supplementation and body weight gain, plasma triglyceride, and total fat mass (Handayani
et al., 2011). A similar study in mice has also reported that consumption of either a hot
water extract or ethanol extract of Hericium erinaceus improved lipid metabolism in mice
fed a high-fat diet. Administration of either the water-extract or ethanol-extract with a high
fat diet for 28 days resulted in a marked decrease in body weight gain, fat weight as well
as blood and hepatic triacylglycerol levels (Hiwatashi et al., 2010).
A study has been conducted to investigate the hypocholesterolemic effect of a hot-water
fraction (HW) from cultured mycelia of Cordyceps sinensis. In mice fed a cholesterol-free
diet and those fed a cholesterol-enriched diet, body and liver weights were not
significantly different from those of the controls. The serum total cholesterol (TC) of all
mice groups administered HW (150 and 300mg/kg/d, respectively) with the cholesterolenriched diet decreased more than in the control group. Among the mice fed the
cholesterol-enriched diet, HW also increased the high-density lipoprotein (HDL)
cholesterol level, but decreased the very low-density lipoprotein plus low-density
lipoprotein (VLDL+LDL) cholesterol level. The changes in HDL-and VLDL+LDLcholesterol levels consequently decreased the atherogenic value. The results indicated
that HW in rats administered a cholesterol-enriched diet decreased the plasma cholesterol
112
level. The 300mg/kg dose had a significant effect on the serum total cholesterol level (Koh
et al., 2003).
Anti-atherosclerotic effects of Pleurotus eryngii (Eringi), Grifola frondosa (Maitake), and
Hypsizygus marmoreus (Bunashimeji), have been demonstrated in atherosclerosissusceptible C57BL/6J, apolipoprotein E-deficient (apoE(-/-)) mice. Atherosclerotic lesions
were significantly decreased in the 3 mushroom groups compared to the control group.
The anti-atherosclerotic effect was partially via lowering of serum total cholesterol
concentrations (Mori et al., 2008). Agaricus sylvaticus has also been reported to prevent
the onset of atheroma plaques in hypercholesterolemic rabbits (Percario et al., 2008).
Auricularia auricula polysaccharides have also recently been reported to have a positive
effect on heart function of aged mice, possibly via their significant antioxidant activity (Wu
et al., 2010).
11.2 Animal model (rat and larger animal) studies

Maitake mushroom extracts have been suggested to ameliorate progressive hypertension
in female Sprague-Dawley rats via an effect on systolic blood pressure that may, at least
in part, involve the renin-angiotensin system (Preuss et al., 2010). Blood pressure of
spontaneously hypertensive rats (SHR) has been shown to be significantly reduced by
Maitake feeding for 8 weeks, beginning at a time when the animals were 10 weeks of age
with well-established high blood pressure. There was no difference in the plasma total and
free cholesterol, triglyceride and phospholipid levels between the Maitake fed animals and
the control. Conversely, Shiitake mushroom intake did not reduce blood pressure, but
significantly lowered free plasma cholesterol, triglyceride and phospholipid in comparison
to the control (Kabir and Kimura, 1989). A single dose of gamma-aminobutyric acid
(GABA) enriched Flammulina velutipes (Enokitake) powder (0.9 mg GABA/kg) has also
113
been shown to result in a significant lowering of systolic blood pressure ( by 30 mmHg) in

spontaneously hypertensive rats (SHR), but no effects were observed in rats with normal
blood pressure (Harada et al., 2011).
The effects of Shiitake (Lentinus edodes, LE) and autolyzed- (fermented-) Shiitake
(autolyzed-LE) on blood pressure and serum fat levels of spontaneously hypertensive rats
(SHR) have been studied. The animals of the autolyzed-LE group showed significantly
lower blood pressure compared to the control or LE group. The serum levels of total
cholesterol (TC), triglyceride and phospholipid of the groups fed with LE and autolyzed-LE
were lower than those of the control group, and atherogenic index [(TC-HDL-C)/HDL-C]
improved significantly in 21 days. It was suggested that the serum TC decline is the action
of eritadenine that is contained in the Shiitake mushroom. An inhibitory activity of the
angiotensin I-converting enzyme (ACE) was compared between of LE and autolyzed-LE.
Autolyzed-LE showed higher inhibitory activity than LE against the ACE. The results
suggested that the hypotensive action of autolyzed-LE was due to concomitant ACE
inhibitory activities of peptides and gamma-aminobutyric acid contained in higher amounts
during the autolysis of LE (Watanabe et al., 2002).
Feeding hypercholesterolemic Sprague-Dawley albino rats a diet containing 5% fruiting
bodies of Pleurotus nebrodensis reduced plasma total cholesterol, triglyceride, low-density
lipoprotein, total lipid, phospholipids and LDL/HDL ratio by 31.01, 47.71, 62.50, 31.91,
24.65 and 53.06%, respectively, with significant reductions in body weight. No adverse
effects were reported on plasma albumin, total bilirubin, direct bilirubin, creatinin, blood
urea nitrogen, uric acid, glucose, total protein, calcium, sodium, potassium, chloride,
inorganic phosphate, magnesium, or enzyme profiles. The feeding of these mushrooms
increased total lipid and cholesterol excretion in feces. The data suggest that P.
nebrodensis was acting on the atherogenic lipid profile in these hypercholesterolemic rats
(Alam et al., 2011b). Essentially identical results were also reported for Pleurotus ferulae
in the same animal model (Alam et al., 2011c).
A hypocholesterolemic effect has been shown with Oyster mushrooms (Pleurotus
ostreatus) in rats with Streptozotocine-induced diabetes. Oyster mushroom (4% dry oyster
mushroom fruit body) lowered cholesterol content by more than 60% in the liver although
it did not significantly affect either the serum triacylglycerol level or the content in liver
(Bobek et al., 1991). Similar results have been observed in rats with a hereditary
hypersensitivity to dietary cholesterol (Bobek et al., 1990). The hypocholesterolemic
effects of Oyster mushrooms has been demonstrated to be dose-dependent (Bobek et al.,
114
1997). A similar hypocholesterolemic effect of the oyster mushroom (Pleurotus ostreatus)

was also observed in hamsters (Bobek et al., 1993b) and in rabbits (Bobek and Galbavy,
1999).
Hypocholesterolemic activity of the agent eritadenine present in Lentinus edodes has
been reported (Enman et al., 2007). Hypocholesterolemic activity by Hatakeshimeji
(Lyophyllum decastes Sing.) mushroom has been demonstrated in rats (Ukawa et al.,
2001b), and by Ganoderma lucidum in hamsters and mini-pigs (Berger et al., 2004). Other
mushroom varieties that have been shown to have hypocholesterolemic properties include
Volvariella volvacea (straw mushroom) (Cheung, 1998, Cheung, 1996a), Auricularia
auricula (Tree-ear) and Tremella fuciformis (White jelly-leaf) (Cheung, 1996b) and
Pleurotus ostreatus (Oyster mushroom) (Hossain et al., 2003). In contrast to the above
studies, farm-grown Agaricus campestris in the diet of rats did not affect plasma and liver
cholesterol concentrations (Beynen et al., 1996).
Plasma cholesterol concentration in rats has been shown to be reduced by feeding of
mushroom (Agaricus bisporus) fibre. The results demonstrated that mushroom fiber (and
sugar beet fiber) lowered the serum total cholesterol level by enhancement of the hepatic
low density lipoprotein (LDL) receptor mRNA (Fukushima et al., 2000). Similar cholesterollowering effects in rats of Maitake (Grifola frondosa) fiber, Shiitake (Lentinus edodes)
fiber, and Enokitake (Flammulina velutipes) fiber have also been reported (Fukushima et
al., 2001).
The effects of four edible mushrooms (Shiitake, Hiratake, Eringi, Hatakeshimeji) on serum
and hepatic lipid levels have been investigated in rats. The results showed that the body
weight and food intake of the four mushroom groups were significantly lower than those of
the control group. The liver level of triacylglycerols was significantly lower in the Hiratake,
Eringi and Hatakeshimeji groups than that in the control group. The serum cholesterol
levels of the mushroom groups were also significantly lower than that of the control group
showing that these four edible mushrooms suppress hepatic triacylglycerol accumulation,
and lower blood lipid levels (Ohtsuki et al., 2006). The Bunashimeji mushroom
(Hypsizigus marmoreus) has also been shown to suppress hepatic triacylglycerols
accumulation and lowers blood cholesterol levels in mice (Ohtsuki et al., 2007). Exobiopolymers (EXBP) produced from a submerged mycelial culture of Ganoderma lucidum
has also bben shown to lower liver total cholesterol, triglyceride, and phospholipid levels
by 22.4, 23.1, and 12.9%, respectively. Furthermore, the high-density lipoprotein (HDL)
cholesterol and ratio of HDL cholesterol to total cholesterol were significantly increased
115
(Yang et al., 2002b).

Maitake mushroom consumption has also been shown, in Sprague-Dawley rats, to have
the ability to alter lipid metabolism by inhibiting both the accumulation of liver lipids and
the elevation of serum lipids. Further studies are needed to determine the mechanism of
activity of Maitake mushrooms and to establish whether their action in humans is similar to
that observed in the rat model (Kubo and Nanba, 1996). A further study by the same
group, using the same rat model system, has also shown that consumption of dried
Maitake powder (mixed with a basic high-cholesterol rat chow) cholesterol, triglyceride
and phospholipids in the serum of rats in the Maitake-feed group were suppressed by 0.30.8 times those in animals fed the basic feed. Weights of liver and epididymal fat-pads
were significantly lower (0.6-0.7 times) than those in the basic feed group, indicating that
Maitake inhibited lipid accumulation in the body. Liver lipids were also measured and the
values were found to be decreased by Maitake administration. Measurement of the
amount of total cholesterol and bile acid in faeces showed the ratio of cholesterolexcretion had increased 1.8 fold and bile acid-excretion 3 fold by Maitake treatment
suggesting that Maitake consumption may help to improve the lipid metabolism as it
inhibits both liver lipid and serum lipids which were increased by the ingestion of high-fat
feed (Kubo and Nanba, 1997).
The straw mushroom Volvariella volvacea has been reported to produce a hypotensive
response in animals. An aqueous extract of the mushroom (SME) was prepared and given
through intravenous injections to normotensive rats. The blood pressure changes
produced by SME alone or in the presence of various drugs were studied. An i.v. injection
of SME produced a hypotensive effect in rats with an ED50 of 25mg dry weight/kg body
weight. SME did not increase urinary excretion or sodium diuresis. It produced positive
chronotropic and inotropic effects on isolated right atria and induced contraction of
isolated tail artery strips. This latter contractile response was inhibited by antagonists of
serotonin and alpha-adrenoceptor, ketanserin and phentolamine respectively. Partial
purification using dialysis and liquid chromatography revealed that the hypotensive active
substances had molecular weights between 8,000 -12,000 daltons and were heat stable
and resistant to trypsin digestion (Chiu et al., 1995).
116

Agaricus bisporus (white button and crimini), Lentinula edodes (shiitake), Pleurotus
ostreatus (oyster), and Grifola frondosa (maitake) mushrooms have been shown to inhibit
adhesion molecule expression and in vitro binding of monocytes to human aortic
endothelial cells under pro-inflammatory conditions, which are associated with
cardiovascular disease (Martin, 2010b). A further study by the same group reported that
ergothioneine, an antioxidant present in edible mushrooms, was able to interrupt proinflammatory induction of adhesion molecule expression associated with atherogenesis,
and to inhibit monocyte binding to endothelial cells characteristic of early cardiovascular
disease (Martin, 2010a). An extract from Hypsizygus marmoreus has also been shown to
inhibit platelet aggregation induced by collagen suggesting that it may have an effect
against platelet related cardiovascular disease (Park et al., 2011).
Angiotensin-converting enzyme (ACE) inhibitory activity (which has an effect on blood
pressure reduction) has been demonstrated in the culture broth from Flammulina velutipes
(strain 414). Nutritional requirements for the production of ACE inhibitory activity from F.
velutipes were shown to include sucrose, ammonium acetate, and glutamic acid (Kim et
al. 2002). Production and characterization of an anti-hypertensive angiotensin Iconverting enzyme inhibitor has also been reported from Pholiota adiposa (Koo et al.,
2006) and Hatakeshimeji (Lyophyllum decastes Sing.) (Ukawa et al., 2001a).
An aqueous extract of Ganoderma lucidum has been shown to possess ACE inhibitory
activity (IC50 = 50 mg/mL) in vitro (Abdullah et al., 2012). Two different ACE inhibitors
(oligopeptides) from Pleurotus cornucopiae have been identified with IC50 values of 0.46
and 1.14 mg/ml. The amino acid sequences of the two purified oligopeptides were
RLPSEFDLSAFLRA and RLSGQTIEVTSEYLFRH. The molecular mass of the purified
ACE inhibitors was estimated to be 1622.85 and 2037.26 Da, respectively. Water extracts
of the P. cornucopiae fruiting body also showed a clear antihypertensive effect on
spontaneously hypertensive rats at a dosage of 600 mg/kg (Jang et al., 2011a).
Reactive oxygen free radicals have been reported to be important in ischemia-reperfusion
injury cascades. Agaricus Blazei Murill (ABM) extract, previously reported to modulate
oxidative stress, increased the survival of rat cardiomyocytes (H9c2 cell line) without
cytotoxicity. Pretreatment with ABM extract reduced hydrogen peroxide-induced cell
117
damage and increased cell survival. ABM-pretreated rats that underwent myocardial
ischemia-reperfusion had greatly reduced infarct areas compared to those in the control
group. ABM may have a cardioprotective effect by increasing antioxidant activity, which
greatly ameliorates myocardial injuries caused by myocardial ischemia-reperfusion
injuries (Huang et al., 2010a).
11.4 Summary of Cardiovascular Health

Plasma cholesterol in animal models has been shown to be reduced by mushroom
consumption. The hypocholesterolemic effect appears to be due partly to an increased
rate of low density lipoprotein (LDL) and high-density lipoprotein (HDL) catabolism. While
some studies have postulated eritadenine or angiotensin I converting enzyme inhibitory
peptides as the hypocholesterolemic agents, similar effects on cholesterol, and other
biomarkers of cardiovascular risk, have been demonstrated by consumption of mushroom
(e.g. Agaricus bisporus) fibre. Such a cholesterol-lowering effect has also recently been
reported in humans.
.
12. Effects on Neurodegenerative Diseases / Cognition

The effects of Hericium erinaceus on amyloid beta
(25-35) peptide-induced learning and memory
deficits in mice have been evaluated. Mice were
administered 10 g of amyloid beta (25-35) peptide
intracerebroventricularly on days 7 and 14, and fed
a diet containing H. erinaceus over a 23-d
experimental period. Memory and learning function
was examined, with H. erinaceus preventing
impairments of spatial short-term and visual recognition memory induced by the amyloid
beta(25-35) peptide (Mori et al., 2011).
Cognitive enhancing and antioxidant activities of Inonotus obliquus (Chaga) have been
evaluated against scopolamine-induced experimental amnesia in mice. A methanol
118
extract of Chaga (MEC) at 50 and 100 mg/kg doses was administered orally for 7 days to
amnesic mice. To elucidate the mechanism of the cognitive enhancing activity of MEC,
the activities of acetylcholinesterase (AChE), anti-oxidant enzymes, the levels of
acetylcholine (ACh) and nitrite of mice brain homogenates were evaluated. MEC
treatment for 7 days significantly improved the learning and memory. The significant
cognitive enhancement observed in mice after MEC administration was closely related to
higher brain anti-oxidant properties and inhibition of AChE activity (Giridharan et al.,
2011).
Treatment of mice with Hericium erinaceum (H. erinaceum) (300 mg/kg for 14 days) prior
to middle cerebral artery (MCA) occlusion, protected against focal cerebral ischemia, by
increasing nerve growth factor levels suggesting that H. erinaceum and its components
could be useful for preventing cerebral infarction (Hazekawa et al., 2010). In a rat model
of permanent focal cerebral ischemia (using Sprague-Dawley rats), a filtrate of Phellinus
linteus broth significant reduced cortical infarct volume 30 and 60 minutes before onset of
cerebral ischemia compared with the control group, while post-treatment (30minutes after
ischemic onset) also significantly reduced cortical infarct volume. A significant benefit of
this neuroprotective effect was a wide therapeutic time window since significant infarct
volume reduction was obtained by administration, even after the ischemic event (Suzuki et
al., 2011).
Cordymin, a peptide purified from the medicinal mushroom Cordyceps sinensis has been
reported to have a neuroprotective effect in the ischemic brain, which is due to the
inhibition of inflammation and increase of antioxidants activity related to lesion
pathogenesis (Wang et al., 2012b).
Reactive oxygen species have been reported to be involved in the pathogenesis of a
number of age-associated human health conditions. The mitochondrial respiratory chain is
a direct intracellular source of reactive oxygen species. Ganoderma lucidum (50 and 250
mg/kg) has been shown to enhance the activities of mitochondrial dehydrogenases and
complex I and II of the electron transport chain in the brain of aged male Wistar rats (Ajith
et al., 2009). The level of lipid peroxidation was significantly lowered in the Ganoderma
lucidum treated group compared to the aged controls. The activity exhibited by the extract
of Ganoderma lucidum was partially correlated to its antioxidant activity. If Ganoderma
lucidum is able to improve the function of mitochondria in the aged rat brain, then further
studies would be warranted to evaluate possible future applications against ageing
associated neurodegenerative diseases.
119

A recent study has compared the effect of the fruiting body and mycelium of Antrodia
camphorata on alleviating the A-beta40-induced neurocytotoxicity in an in vitro A-betadamaged neuron cell model (PC-12 cell treated with A-beta40) and memory impairment in
ab in vivo Alzheimer's disease (AD) animal model induced with a continuous brain infusion
of A-beta40. The fruiting body possessed stronger anti-oxidative and anti-inflammatory
abilities for inhibiting neurocytotoxicity in A-beta40-treated PC-12 cells and A-beta40
accumulation in A-beta40-infused brain than mycelium. Hyper-phosphorylated tau (p-tau)
protein expression, known as an important AD risk factor, was suppressed by the
treatment of the fruiting body rather than that of mycelium demonstrating that the fruiting
body resulted in a more significant improvement on working memory ability than mycelium
in the AD rat model (Wang et al., 2012c).
12.3 Summary of Neurodegenerative Diseases / Cognition

Although very preliminary, new data showing protective effects of mushrooms on betaamyloid peptide toxicity in the brain and mild cognitive impairment (both precursors to
dementia) are very exciting and warrant further research on the ability of mushroom
consumption to delay the onset of dementia / Alzheimers disease.
13. Effects on Dental Health

A recent study has evaluated an array of plant foods with a potential activity on the
development of microbial oral diseases. Fractionation on the basis of molecular mass
(MM), of water-soluble components revealed that mushroom extract had a high potential
against oral pathogens, with the lower MM fractions showing higher activity that the high
MM fractions (Daglia et al., 2011). Another very similar study has also shown that low
molecular mass (LMM) fractions from extracts of Shiitake mushrooms (as well as from
raspberry and red chicory) have been shown to be a useful source of specific
antibacterial, anti-adhesion/coaggregation, and anti-biofilm agent(s) that may be used for
protection towards caries and gingivitis. Each of the LMM fractions tested prevented or
reduced the induction of gene expression of the periodontal pathogens Prevotella
120
intermedia and Actinomyces naeslundii, suggesting that these LMM fractions could
modulate the effects of bacteria associated with periodontal disease in gingival cells
(Canesi et al., 2011). Furthermore, a study has compared the effectiveness of Shiitake
mushroom extract against the active component in a leading gingivitis mouthwash,
containing chlorhexidine, in an artificial mouth model (constant depth film fermenter). The
total bacterial numbers as well as numbers of eight key taxa in the oral environment were
investigated over time. The results indicated that Shiitake mushroom extract lowered the
numbers of some pathogenic taxa without affecting the taxa associated with health, unlike
chlorhexidine which had a limited effect on all taxa (Ciric et al., 2011). Quinic acid from
mushrooms has also been suggested to have anticaries activity (Gazzani et al., 2011).
14. Effects of Eye Health

The efficacy of a Pleurotus ostreatus extract in preventing selenite-induced cataractogenesis
has been evaluated. In vitro, simultaneous incubation of extract with selenite-challenged lenses
caused a decrease in lens opacification by maintaining antioxidant components at near normal
levels. In vivo, P.ostreatus prevented cataracts in 75% of rats (Isai et al., 2009).
A study using isolated goat eye lens has reported that an extract of Pleurotus florida was
able to prevent glucose-induced cataract in this in vitro model system (Aditya et al., 2011).
15. Effects on Immune Function

It has been demonstrated that dietary supplementation
with white button mushrooms (Agaricus bisporus)
enhances natural killer (NK) cell activity in C57BL/6
mice, suggesting that increased intake of white button
mushrooms may promote innate immunity against
tumours and viruses through the enhancement of NK
activity (Wu et al., 2007a). Agaricus bisporus has been
shown to enhance maturation of bone marrow-derived
dendritic cells of C57BL mice. A functional assay for dendritic cell maturation showed that
mushroom supplementation decreased cell endocytosis and increased intracellular
121
interleukin (IL)-12 levels suggesting an enhancement of both innate and T cell-mediated

immunity leading to a more efficient surveillance and defence mechanism against
microbial invasion and tumour development (Ren et al., 2008b).
2-Amino-3H-phenoxazin-3-one (APO) from an extract of Agaricus bisporus IMBACH has
been shown to inhibit NO production by mouse peritoneal macrophages in response to
the pro-inflammatory stimuli lipopolysaccharide (LPS) and interferon (IFN)-gamma
(LPS/IFN-gamma) at low concentrations (IC50=1.5 M) through reduced inducible NO
synthase protein expression. APO inhibited both cyclooxygenase (COX)-1 and COX-2
enzyme activities with almost equal selectivity (Kohno et al., 2008).
Oral administration of 10mg/kg of an immunomodulatory protein (termed FVE) purified
from Enoki mushroom (Flammulina velutipes) and known as an activator for human T
lymphocytes, significantly increased the life span and inhibited the tumor size of BNL
1MEA.7R.1 (BNL) hepatoma-bearing mice. Oral administration of FVE displayed antitumor activity through activating both innate and adaptive immunity of the host to prime a
cytotoxic immune response and IFN-gamma played a key role in the anti-tumor efficacy of
FVE (Chang et al., 2010b).
Polysaccharides from Flammulina velutipes have also been shown to promote the
metabolic activity of murine splenocytes and peritoneal exudate cells (PEC) and increase
the amounts of TNF-alpha, INF-gamma and IL-2 in the supernatants of splenocyte
cultures, and the amount of TNF-alpha in PEC cultures, with the most marked increase on
TNF-alpha level. Flammulina velutipes polysaccharides (100, 50, 25 mg/kg) raised the
serum levels of TNF-alpha and INF-gamma in Sarcoma-180 tumour-bearing mice.
Flammulina velutipes polysaccharides may regulate murine immune function through
promoting the production of TNF-alpha, INF-gamma and IL-2 (Chang et al., 2009a). A
beta-glucan from Agrocybe chaxingu significantly inhibited lipopolysaccaride (LPS)induced nitric oxide (NO) and cyclooxygenase-2 (COX-2) expression levels in murine
macrophage Raw 264.7 cells. Furthermore, topical application of the polysaccharide
resulted in marked inhibition of 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced ear
edema in mice. These results suggest that this polysaccharide may be useful for the
treatment of NO- and COX-2-related disorders such as inflammation (Lee et al., 2009a).
Ganoderma lucidum (Leyss: Fr) Karst. has also been shown to trigger immunomodulatory
effects and reduce nitric oxide synthesis in Swiss male mice (Rubel et al., 2010)
122
Oral administration of a protein from Flammulina velutipes has also been shown to
possess anti-tumor activity in mice through activation of both innate and adaptive
immunity of the host to prime a cytotoxic immune response with interferon-gamma having
an effect on the anti-tumor efficacy of the protein (Chang et al., 2010a).
Using apolipoprotein E-deficient (ApoE(-/-)) mice, an experimental model of
atherosclerosis, the effects of supplementation of mice with Agaricus blazei for 6 or 12
weeks has been studied on the activation of immune cells in the spleen and blood and on
the development of atherosclerosis. Food intake, weight gain, blood lipid profile, and
glycemia were similar between the control and supplemented groups. To evaluate
leukocyte homing and activation, mice were injected with radiolabeled leukocytes, which
showed enhanced leukocyte migration to the spleen and heart of A. blazei-supplemented
animals. Analysis of the spleen showed higher levels of activation of neutrophils, NKT
cells, and monocytes as well as increased production of TNF-alpha and IFN-gamma.
Circulating NKT cells and monocytes were also more activated in the supplemented
group. Atherosclerotic lesion areas were larger in the aorta of supplemented mice and
exhibited increased numbers of macrophages and neutrophils and a thinner fibrous cap.
A. blazei-induced transcriptional upregulation of molecules linked to macrophage
activation (CD36, TLR4), neutrophil chemotaxy (CXCL1), leukocyte adhesion (VCAM-1),
and plaque vulnerability (MMP9) were seen after 12 weeks of supplementation. The data
show that the immunostimulatory effect of A. blazei has proatherogenic repercussions. A.
blazei enhanced local and systemic inflammation, upregulating pro-inflammatory
molecules, and enhancing leukocyte homing to atherosclerosis sites without affecting the
lipoprotein profile (Goncalves et al., 2011).
Alpha-glucan-beta-glucan-protein complex polysaccharide from Agaricus blazei
administered intraperitoneally or orally to Sarcoma 180 transplanted mice had no direct
cytotoxic action on tumour cells in vitro. However, the polysaccharide showed a strong in
vivo tumour growth-inhibitory effect suggesting that the effect of the polysaccharide is due
to host-mediated mechanisms (Gonzaga et al., 2009). There is growing evidence that
such effects of a variety of mushrooms are mediated via promotion of natural immunity
though macrophages, dendritic cells and NK cells. These cells attack cells infected with
pathogens such as bacteria and viruses and produce cytokines, such as interferongamma (IFN-), which can modulate natural and specific immune responses.
Gandoderma lucidum extracts have also been shown to promote immune responses in
normal BALB/c mice (Chang et al., 2009a) and WEHI-3 leukemic BALB/c mice (Chang et
al., 2009b)
123
A polysaccharide extracted from the Maitake mushroom (Grifola frondosa S.F. Gray) has
been shown to stimulate natural immunity in normal C3H/Hej mice. This effect was related
to the activation of NK cells indirectly through IL-12 produced by macrophages and
dendritic cells (Kodama et al., 2003). A subsequent study from this group has suggested
that the mechanism by which NK cells are activated is mediated through cytokines
produced by antigen-presenting cells (Kodama et al., 2010). In Sarcoma-180-bearing
mice, proteoglycans from Pleurotus ostreatus mycelia, have been shown to elevate
mouse natural killer (NK) cell cytotoxicity and stimulated macrophages to produce nitric
oxide (Sarangi et al., 2006).
A study has also suggested that oral administration of a submerged cultivated G. frondosa
mixture to normal mice may enhance host innate immunity against foreign pathogens
without eliciting an adverse inflammatory response (Wang et al., 2008).
An extract of Cordyceps militaris has been shown to suppress dextran sodium sulphate
(DSS)-induced acute colitis in mice and production of inflammatory mediators from
macrophages and mast cells. The extract significantly attenuated DSS-induced body
weight loss, diarrhea, gross bleedingand, prevented shortening of colon length and crypt
length, and suppressed epithelial damage, loss of goblet cells, loss of crypts, and
infiltration of inflammatory cells induced by DSS. In addition, the extract inhibited iNOS
and TNF-alpha mRNA expression in colon tissue of DSS-induced colitis and in RAW264.7
cells. Cordyceps militaris extract suppressed degranulation of mast cells in the colon of
mice with DSS-induced colitis and in antigen-stimulated mast cells. The data suggest that
the extract from Cordyceps militaris has anti-inflammatory activity in DSS-induced acute
colitis by down-regulating production and expression of inflammatory mediators (Han et
al., 2011).
The induction of granulocyte macrophage colony-stimulating factor (GM-CSF) production
by water-soluble, polysaccharide components of Ganoderma lucidum (Reishi) mycelia,
possibly providing an anti-inflammatory effect in a mouse model of colitis has also been
reported (Hanaoka et al., 2011).
Letinus edodes has been shown to have immunomodulating effects which are mediated
via the enhancement of type-1 helper T cell-mediated cellular immunity (Hyun Ji et al.,
2011). Intake of Lentinula edodes mycelia extract significantly inhibited tumor growth in
C57BL/6 mice inoculated with B16 melanoma, and this in vivo anti-tumor effect was not
124
observed in nude mice, suggesting a T cell-dependent mechanism. Oral ingestion of

Lentinula edodes extract restored immune responses of class I-restricted and melanomareactive CD8(+) T cells in these melanoma-bearing mice, possibly via a mitigation of T
cell-mediated immunosuppression (Tanaka et al., 2011).
Letinula edodes extracts have been dispersed with lecithin micelles to prepare superfine
particles (0.05 to 0.2 microns in diameter) of beta-1,3-glucan (micellary mushroom
extracts). When mice were fed with these micelles of beta-glucan (0.75mg/day/mouse,
smaller amounts of beta-glucan), the number of lymphocytes yielded by the small intestine
increased by up to 40% and tumour cytotoxicity against P815 cells and cytokine
production was also augmented, suggesting that smaller amounts of micellary beta-glucan
might be useful for the potentiation of intestinal immunity (Shen et al., 2007). The Letinula
edodes (Shiitake) mushroom-derived immuno-stimulant lentinan has also been reported
to protect against murine malaria blood-stage infection by evoking adaptive immuneresponses (Zhou et al., 2009).
Oral administration of an endo-polysaccharide of Phellinus igniarius inhibited the growth of
Sarcoma 180 and Hepatoma 22 cells that were implanted in mice, and increased the life
span. Serum IL-2 and IL-18 were significantly increased in the Sarcoma 180 implanted
mice fed with the endo-polysaccharide at 500 mg/kg and 250 mg/kg compared with those
in control. The concentrations of serum IL-2 only were significantly increased in Hepatoma
22 implanted mice using the same doses (Chen et al., 2011b), suggesting that the antitumor effect was mediated via enhancement of cell mediated immunity.
Phellinus linteus contains constituents that exhibit potent anti-tumour effects through
activation of immune cells. A recent study in mice has reported that boiling water soluble
fractions from mycelium of P.linteus contain anti-allergic and immuno-potentiating
properties (Inagaki et al., 2005). Cordyceps sinensis has also been shown to possess
immuno-potentiating effects in lupus-prone autoimmune (NZB/NZW) mice via action on
peripheral mononuclear T lymphocytes. These effects also reportedly attenuated the
severity of lupus in these mice (Chen et al., 2009). A polysaccharide isolated from
cultured Cordyceps sinensis (named cordysinocan), has been reported to activate
immune responses in cultured T-lymphocytes and macrophages, partly via the induction
of cytokines (Cheung et al., 2009). Orally administered glucans from Pleurotus
pulmonarius have also been recently reported to reduce acute inflammation in dextran
sulfate sodium-induced experimental colitis in mice (Lavi et al., 2010).
125
15.2 Animal model (rat) studies

Agaricoglycerides of the fermented mushroom Grifola frondosa at the dose level of 500
mg/kg has been shown to possess anti-inflammatory and antinociceptive effects in
preclinical animal models of inflammation and in some models of pain (Han and Cui,
2012).
The effects of pleuran, a beta-glucan isolated from Pleurotus ostreatus, have been studied
in a model of acute colitis in rats. Pleuran was given either as a 2% food component or as
0.44% pleuran hydrogel drink over 4 weeks. Colitis was induced by intraluminal instillation
of 4% acetic acid and after 48h the extent of colonic damage and several biochemical
parameters were examined. Pleuran supplementation both in food and in drinking fluid
significantly decreased the disposition to colitis. The enhanced activity of myeloperoxidase
in the inflamed colonic segment was reduced by pleuran diets, reflecting decreased
neutrophil infiltration. The mechanism of the described protective effect of pleuran is not
yet clear, but the authors suggest that the pleuran-enhanced antioxidant defence of the
colonic wall against the inflammatory attack maybe a factor (Bobek et al., 2001).
A protein-bound polysaccharide extracted from Coriolus versicolor has been shown to
have an immuno-potentiating effect, being effective in restoring cyclophosphamide (CPA)induced immuno-suppression such as depressed lymphocyte proliferation, natural killer
cell function, production of white blood cells and the growth of spleen and thymus in rats
as well as in increasing both IgG and IL-2 production on which CPA did not have
significant effects. The protein-bound polysaccharide partly restored CPA-induced
immuno-suppression. The authors suggested that the protein-bound polysaccharide could
be considered as a useful adjuvant, particularly combined with CPA or other
chemotherapy in clinical treatment of cancer patients. The mechanism by which the
protein-bound polysaccharide restored the immuno-suppression induced by CPA is
unclear (Qian et al., 1997).
15.3 In vitro studies (human cell lines)

immune function with implications for inhibitory effects on tumour growth. Some of the
more efficacious compounds have been reported to be 1,6-branched 1,3--glucans which
have been reported to inhibit tumour growth by stimulating of the immune system via
effects on NK cells, macrophages and via T cells and their cytokine production. More
126
recent work has implicated polysaccharides with varying sugars and some are - rather
than -glucans. Furthermore, mushroom proteins, terpenes and furans have also been
implicated in immune function. While considerable in vitro data have been generated, in
vivo studies are few and the small number of clinical studies that have been carried out
have have often been poorly controlled and with small numbers of patients. The
immunobiology of mushrooms has been reviewed (Borchers et al., 2008), as have the
health effects of beta-glucans in mushrooms (Rop et al., 2009, Rondanelli et al., 2009).
Innate immune cells are activated by the binding of beta-glucan to the dectin-1 receptor.
Ganoderma lucidum binds to dectin-1 and has been shown to induce RAW264.7 mouse
macrophage cell secretion of several cytokines, including granulocyte colony-stimulating
factor, interleukin (IL)-6, regulated upon activation normal T cell expressed and secreted
(RANTES), tissue inhibitor of metalloproteinase-1, and tumor necrosis factor-alpha.
Ganoderma lucidum also induced both nitric oxide and inducible nitric oxide synthase
(iNOS). Treatment with an inhibitor of nuclear factor-kappa B (NF-kappa B) reduced the
induction of IL-1, IL-6, and iNOS in a concentration-dependent manner and expression of
toll-like receptor (TLR)2, TLR4, and TLR6 was increased by Ganoderma lucidum
treatment. The result indicates that Ganoderma lucidum induces macrophage secretion of
inflammatory cytokines, which was also potentiated by the presence of
lipopolysaccharide, likely by binding to dectin-1 and toll-like TLR-2/6 receptors, which
activate NF-kappa B and prompt the secretion of cytokines (Batbayar et al., 2011).
An Agaricus brasiliensis-derived cold water extract has also been reported to have some
water-soluble toll-like receptor ligand complexes and induce cytokine production via a tolllike receptor 2-dependent mechanism (Yamanaka et al., 2011). A polysaccharide
(cordlan) isolated from Cordyceps militaris has also been shown to induce dendritic cell
maturation through toll-like receptor 4 (TLR-4) signalling cascades (Hyung Sook et al.,
2010).
Polysaccharide krestin (PSK) is an extract from Trametes versicolor, that has been shown
to be a selective toll-like receptor TLR2 agonist (Lu et al., 2011a), and the activation of
dendritic cells (DC) and T cells by PSK is dependent on TLR2. Oral administration of PSK
in neu transgenic mice significantly inhibited breast cancer growth, with the antitumor
effect of PSK being dependent on both CD8(+) T cell and NK cells, but not CD4(+) T cells.
PSK did not inhibit tumor growth in TLR2(-/-) mice suggesting that the antitumor effect is
mediated by TLR2. The data indicate that PSK is a specific TLR2 agonist and has potent
antitumor effects via stimulation of both innate and adaptive immune pathways (Lu et al.,
2011b). Components of PSK have also been reported to act as ligands for TLR4 receptors
127
leading to induction of TNF-alpha and IL-6 inflammatory cytokines (Price et al., 2010).
PSK has also been reported to reduce toxicity of current treatments used in patients with
metastatic colorectal cancer (Shibata et al., 2011). The effects of PSK in cancer therapy
and the possible mechanism of action have recently been reviewed (Sun et al., 2012).
Two polysaccharide fractions (designated as ABP-1 and ABP-2) isolated from Agaricus
bisporus have been shown to stimulate the production of nitric oxide, interleukin-6, and
tumor necrosis factor-alpha. Modulation of macrophage function by A. bisporus
polysaccharides was mediated in part through activation of nuclear factor-kappaB. Both
ABP-1 and ABP-2 had the ability to inhibit the growth of human breast cancer MCF-7 cells
but had little effect on the growth of human colon, prostate, gastric cancer, and murine
Sarcoma 180 cells. However, when murine Sarcoma 180 cells exposed to ABP-1 or ABP2 were implanted subcutaneously into mice, a reduction in tumor growth was observed
compared with that observed in control mice. These data provide evidence that
macrophages possibly contribute to the antitumorigenic effects of Agaricus bisporus
polysaccharides (Jeong et al., 2012, Sang Chul et al., 2012). Beta-glucan-rich
polysaccharide extracts from Agaricus bisporus (but not A. blazei Murill, Phellinus linteus,
Coprinus comatus, or spores of Ganoderma lucidum) stimulated nitric oxide production by
bone marrow-derived macrophages. It has been suggested that branching of the betaglucan chain is essential for immune-stimulating activity (Volman et al., 2010a).
Methanol extracts from Agaricus bisporus, Boletus edulis, Cantherellus cibarius,
Cratarelluscornucopioides, Lactarius deliciosus and Pleurotus ostreatus have shown antiinflammatory activity in LPS activated RAW 264.7macrophages. A. bisporus, C. cibarius
and L.deliciosus exhibited the higher anti-inflammatory activities inducing inhibition of NO
production and iNOS, IL-1beta and IL6 mRNAs expression in response to LPS stimulation
(Moro et al., 2012).
Lentinan, a cell wall beta-glucan from the fruiting bodies of Lentinus edodes has been
reported to exert its immunomodulating activity (in RAW 264.7 macrophages) by
activation of MAPK signaling pathways without secretion of TNF-alpha and NO (Xu et al.,
2011a).
Water-soluble extracts isolated from Hypsizigus marmoreus have been shown to
significantly stimulate Raw 264.7 cancer cells to release nitric oxide and prostaglandin E2,
suggesting their potential immunomodulating activities (Bao and You, 2011). A further
study from the same group has subsequently also shown that alkali-soluble proteoglycans
128
and acid-soluble proteoglycans from Hypsizygus marmoreus significantly stimulated

Raw264.7 cells to release nitric oxide, prostaglandin E2 as well as cytokines, such as IL-1
beta, TNF-alpha and IL-6 by inducing mRNA expression (Bao et al., 2012).
Another study in Raw 264.7 cells, has evaluated anti-inflammatory effects of a bioactive
nonlectin glycoprotein (PCP-3A) isolated from the fresh fruiting body of the golden oyster
mushroom, Pleurotus citrinopileatus. The results showed that PCP-3A failed to affect
RAW 264.7 viability at a concentration up to 6.25 g/mL, but inhibited lipopolysaccharide (1
g/mL)-induced expression, and the production of NO and PGE2 in lipopolysaccharideactivated macrophages via the down-regulation of certain pro-inflammatory mediators,
including iNOS and NF-kappaB (Chen et al., 2011a).
Polysaccharides isolated from the fruit bodies and mycelia of both medicinal and edible
mushrooms have been found to exert immunomodulatory function and antitumor activity in
numerous in vivo and in vitro studies, which have recently been summarised in a minireview (Cheung et al., 2011).
The anti-allergenic potential of Pleurotus eryngii extract (PEE) in antigen-stimulated RBL2H3 mast cells has been evaluated with PEE inhibiting allergy markers, including release
of hexosaminidase and histamine, in antigen-sensitized RBL-2H3 cells. PEE also
suppressed the expression and production of interleukin-4 and reduced antigen-induced
NFAT and NF-kappaB transcriptional activity in antigen-sensitized mast cells. PEE also
decreased the levels of proinflammatory cytokines and COX-2 and iNOS expression in
antigen-sensitized mast cells, and suppressed antigen-induced signal protein
phosphorylation of Lyn, PLCgamma2, PKC, Akt, and MAP kinases. The data indicate that
this extract from P. eryngii may provide some insights into the mechanisms for the
possible prevention and treatment of allergic and inflammatory responses (Eun Hee et al.,
2011).
Enhaced proliferation of bone marrow macrophages in adose-dependent manner by
Lingzhi or Reishi medicinal mushroom Ganoderma lucidum immunomodulating substance
(GLIS) has been demonstated. Exposure of bone marrow macrophages to GLIS resulted
in significant increases in NO production, induction of cellular respiratory burst activity,
and increased levels of IL-1 beta, IL-6, IL-12p35, IL-12p40, IL-18, and TNF-alpha gene
expression and levels of TNF-alpha, IL-1 beta, and IL-12 secretion, indicating that GLIS
activates the immune system by modulating cytokine production (Ji et al., 2011, Zhe et al.,
2011).
129
Cordlan polysaccharide from the mushroom Cordyceps militaris has been shown to
induce dendritic cell maturation through toll-like receptor 4 (TLR4) signaling pathways
(Kim et al., 2010a). High 6-branched 1,3-beta-D-glucan has been suggested to activate
dendritic cells via Mitogen Activated Protein Kinase (MAPK) and NF-kappaB signaling
pathways, which are signaling intermediates downstream of TLR4 (Kim et al., 2010b).
However, some immunomodulatory effects of mushrooms do not necessarily depend on
beta-glucan (Lee et al., 2011).
While granulocyte colony stimulating factor (G-CSF) treatment following chemotherapy is
effective in treating against bone marrow myelotoxicity, a beta-glucan extract from the
Maitake mushroom Grifola frondosa (MBG) has been shown to enhance colony forming
unit-granulocyte monocyte (CFU-GM) activity of mouse bone marrow and human
hematopoietic progenitor cells (HPC), and to stimulated G-CSF production. The study
showed that oral MBG promoted maturation of HPC to become functionally active myeloid
cells and enhanced peripheral blood leukocyte recovery after chemotoxic bone marrow
injury (Lin et al., 2010b).
A polysaccharide extracted from Grifola frondosa has been shown to induce cell-mediated
immunity by inducing bone marrow dendritic cell maturation and an antigen-specific Th1
response by enhancing dendritic cell-produced IL-12. Dedritic cells pulsed with colon-26
tumor lysate in the presence of the mushroom polysacchardide induced both therapeutic
and preventative effects on colon-26 tumor development in BALB/c mice (Masuda et al.,
2010). A further study from the same group has demonstrated that a soluble beta-(1,3)
(1,6)-glucan obtained from Grifola frondosa induced cell proliferation and cytokine
production without excessive inflammation in macrophages, supporting its
immunotherapeutic potential (Masuda et al., 2011).
Beta glucan from Grifola frondosa (Maitake) has recently been shown to enhance
umbilical cord blood stem cell transplantation (from full-term infants) in the nonobese
diabetic/severe combined immunodeficient (NOD/SCID) mouse. The Maitake beta glucan
(MBG) enhanced mouse bone marrow (BMC) and human umbilical cord blood (CB) cell
granulocyte-monocyte colony forming unit (GM-CFU) activity in vitro and protected GMCFU forming stem cells from doxorubicin (DOX) toxicity. MBG promoted a greater
expansion of CD34+CD33+CD38- human committed hematopoietic progenitor (HPC)
cells compared to the conventional stem cell culture medium. Oral administration of MBG
to recipient NOS/SCID mice led to enhanced homing at 3 days and engraftment at 6 days
130
in mouse bone marrow compared to control mice. More CD34+ human cord blood cells
were also retrieved from mouse spleen in beta glucan treated mice at 6 days after
transplantation. The studies suggest that Maitake beta glucan promoted hematopoiesis
through effects on CD34+ progenitor cell expansion ex vivo and when given to the
transplant recipient could enhance CD34+ precursor cell homing and support engraftment
(Lin et al., 2009a).
In whole blood, Ganoderma lucidum mycelia have been reported to stimulate tumour
necrosis factor-alpha (TNF-alpha) and IL (interleukin)-6 production after 8h of treatment.
Interferon-gamma release from human whole blood was also enhanced after 3 days of
culture with Ganoderma lucidum mycelia. However, Ganoderma lucidum mycelia did not
potentiate nitric oxide production in RAW264.7 cells (Kuo et al., 2006). The protein
extracts of V. volvacea and G. lucidum have been shown to contain immunomodulating
activity by acting directly on human peripheral blood mononuclear cells and thereby
modulating T cell activation (Jeurink et al., 2008). A protein from Ganoderma lucidum has
also been shown to effectively promote the activation and maturation of immature human
monocyte-derived dendritic cells, preferring a Th1 response, suggesting that the protein
may possess a potential effect in regulating immune responses (Lin et al., 2009b). These
immunomodulatory effects were shown to be mediated via NF-kappaB and Mitogen
Activated Protein Kinase (MAPK) pathways.
A beta-glucan extracted from the fruiting body of the Maitake mushroom (Grifola frondosa)
has been reported to activate cellular immunity and expresses anti-tumour effects, with
the anti-tumour effects relating to its control of the balance between T lymphocyte subsets
Th-1 and Th-2. The fraction decreased the activation of B cells and potentiated the
activation of helper T cells, resulting in enhanced cellular immunity. It also induced the
production of interferon (IFN)-gamma, interleukin (IL)-12 p70, and IL-18 by whole spleen
cells and lymph node cells, but suppressed that of IL-4. These results suggest that this
fraction establishes Th-1 dominance which induces cellular immunity in the population that
was Th-2 dominant due to carcinoma (Inoue et al., 2002). A polysaccharide purified from
Ganoderma lucidum has also been shown to induce gene expression changes in human
dendritic cells and promote T helper 1 immune response in BALB/c mice (Lin et al., 2006).
Agaricus blazei Murill has been reported to possess biological effects that include
immunomodulatory activities, such as stimulation of serum immunoglobulin G level,
delayed-type hypersensitivity, splenocyte proliferation rate, and tumour necrosis factoralpha secretion by splenocytes (Chan et al., 2007). Agaricus blazei has also been
131
reported to have inhibitory effects on mast cell-mediated anaphylaxis-like reactions (Choi

et al., 2006b) and up-regulate genes such as the interleukins IL1B and IL8 (Ellertsen et
al., 2006). An extract of Agaricus blazei Murill has also been reported to differentially
stimulate production of pro-inflammatory cytokines in human monocytes and human vein
endothelial cells in vitro (Bernardshaw et al., 2005a). The effects of Agaricus blazei Murill
on immunity, infection and cancer have been reviewed (Hetland et al., 2008).
Ethyl acetate extracts of Ganoderma applanata, Naematoloma sublateritium, Pleurotus
eryngii, and P. salmoneostramineus have been shown to have in vitro anti-inflammatory
activity via cyclooxygenase-2 inhibitory effects compared to COX-1 inhibition, while ethyl
acetate extracts of Agrocybe cylindracea exhibited high inhibition of the COX-2 enzyme
(Elgorashi et al., 2008). Ceramide from Agrocybe aegerita has also been reported to
inhibit the cyclooxygenase enzymes, COX-1 and -2 (Diyabalanage et al., 2008). In RAW
264.7 macrophage cells, Phellinus linteus butanol fractions (PLBF) inhibit the production
of NO and PGE2 through the down-regulation of inducible NO synthase (iNOS) and
cyclooxygenase-2 (COX-2) gene expression via reactive oxygen species (ROS)-based
NF-kappa B and mitogen-activated protein kinase (MAPK) activation suggesting a
potential effect on inflammation-associated disorders (Kim et al. 2007)(Kim et al.,
2007b).
The immunomodulatory effects of mushrooms appear to be unaffected by food processing
procedures. Boiling (100C, 30 min) and freezing (-80C, 24 h) treatments did not reduce
the effects of Agaricus bisporus lectin (ABL) and the immunomodulatory protein of
Auricularia polytricha on macrophage-activating functionalities, determined by the
induction of TNF- and NO production by RAW264.7 cells in vitro, while treatment with pH
2 and pH 13 buffers only resulted in an insignificant decrease of the induced TNF-a and
NO production. Furthermore, Agaricus bisporus lectin (ABL) and Auricularia polytricha
also withstood vacuum dehydration, with 96.5% and 84.6% of activities being retained,
respectively, in their stimulations of TNF- production. These data show thermal/freezingresistance, acid/alkali tolerance and dehydration stable properties of the extracts tested
with respect to their effects as immune stimulants (Chang et al., 2007).
Possible immuno-modulating effects of Ganoderma lucidum mycelium extract (GL-M) and
spore extracts on human immune cells have been studied. Dendritic cells (DCs) are
antigen-presenting cells and their role in DC-based tumour vaccines has been well
defined. The differential effect of GL-M and GL spore extract (GL-S) on proliferation and
Th1/Th2 cytokine mRNA expression of human peripheral blood mononuclear cells
132
(PBMCs) and monocytes has been evaluated. The effects on the phenotypic and
functional maturation of human monocyte-derived DCs were also investigated. GL-M
induced the proliferation of PBMCs and monocytes, whereas GL-S showed a mild
suppressive effect. Both extracts stimulated Th1 and Th2 cytokine mRNA expression, but
GL-M was a relatively stronger Th1 stimulator. In contrast to GL-S, GL-M enhanced
maturation of DCs in terms of upregulation of CD40, CD80, and CD86, and also reduced
fluorescein isothiocyanate-dextran endocytosis. Interestingly, GL-M-treated DCs only
modestly enhanced lymphocyte proliferation in allogenic mixed lymphocyte culture with
mild enhancement in Th development. The data provide evidence that GL-M has immunomodulating effects on human immune cells and may be of use as a natural adjuvant for
cancer immunotherapy with dendritic cells (Chan et al., 2005). Ganoderma lucidum has
also been shown to enhance the expression of CD40 and CD80 molecules on human
peripheral blood monocytic cells derived from both sexes in a dose-dependent manner
(Ahmadi and Riazipour, 2009).
An immunomodulatory protein (FIP-fve) has been isolated and purified from Flammulina
velutipes. The complete amino acid sequence of FIP-fve was determined by protein
sequencing techniques. FIP-fve consisted of 114 amino acid residues with an acetylated
amino end, and lacked methionine, half-cystine and histidine residues. FIP-fve was able to
hemagglutinate human red blood cells. The immunomodulatory activity of FIP-fve was
demonstrated by its stimulatory activity toward human peripheral blood lymphocytes, and
its suppression of systemic anaphylaxis reactions and local swelling of mouse footpads.
FIP-fve was found to enhance the transcriptional expression of interleukin-2 and
interferon-gamma (Ko et al., 1995).
Phenolic compounds present in mushroom extracts from A. bisporus, A. brasiliensis, and
G. lucidum strongly generated reactive oxygen species (suggesting immunomodulatory
effects) in human PBMCs and K 562 cells in vitro (Wei et al., 2008).
Vitamin D is an important factor for immune function. Mushrooms are a good source of
vitamin D and studies have reported that sunlight-activated biosynthesis of vitamin D from
ergosterols within mushrooms (fresh and dried) can increase vitamin D levels
considerably, which has significant implications in the context of health (Stamets, 2005).
Vitamin D2 levels can also be significantly increased by irradiation of mushrooms with
ultraviolet light (Jasinghe and Perera, 2006) with the effects being proportional to surface
area, e.g. a more efficient way of increasing the vitamin D2 content is to irradiate sliced
mushrooms (Ko et al., 2008). Ganoderma lucidum can biotransform 20%-30% of
133
inorganic Se from substrate with Se being biotransformed preferentially in forms of Secontaining proteins. The immune-regulatory activities of both Se and proteins from G.
lucidum appear to be synergistic (Du et al., 2008).
15.4 Summary of Immune Function

immune function with implications for inhibitory effects on tumour growth. Some of the
more efficacious compounds have been reported to be 1,6-branched 1,3--glucans which
have been reported to inhibit tumour growth by stimulating of the immune system via
effects on natural killer (NK) cells, macrophages and via T cells and their cytokine
production. More recent work has implicated polysaccharides with varying sugars and
some are - rather than -glucans. The mechanisms by which these polysaccharides
exert their immunomodulatory effects are not entirely clear, although structurefunction
relationships have been described between anti-tumor activities and structural
characteristics of -D-glucans. These mushroom polysaccharides generally do not exert
cytotoxic effects on tumor cells, but have been shown to enhance host-mediated
immunomodulatory responses. Furthermore, mushroom proteins, terpenes and furans
have also been implicated in immune function. While considerable in vitro data have been
generated, in vivo studies are few and the small number of clinical studies that have been
carried out have often been poorly controlled and with small numbers of patients.
Mushroom lectins have been reported to be immuno-modulatory proteins. They have
been demonstrated to have thermal/freezing resistance, acid/alkali tolerance and
dehydration stable properties suggesting that they would be stable during food processing
applications and therefore suitable for functional food/health utilization.
16. Effects on Liver Health
Dietary intake of white button mushroom, Agaricus Bisporus has been shown to
significantly lower liver weight and hepatic injury markers in ovariectomized mice (a model
of postmenopausal women). There was less fat accumulation in the livers of mice on the
mushroom diet, and the mice had improved glucose clearance ability. Genes related to
134
the fatty acid biosynthesis pathway, particularly the genes for fatty acid synthetase (Fas)
and fatty acid elongase 6 ( Elovl6), were down-regulated in the liver of mushroom-fed
mice. In vitro mechanistic studies using the HepG2 cell line showed that down-regulation
of the expression of FAS and ELOVL6 by this mushroom extract was through inhibition of
liver X receptor (LXR) signalling and its downstream transcriptional factor SREBP1c
(Kanaya et al., 2011b).
17. Effects on Osteoporosis / Bone Mineral Density

Ethanol extracts of Ganoderma lucidum have been evaluated

against ovariectomized (Ovx)-induced deterioration of bone density
in 11-week-old female Sprague Dawley (SD) rats (Miyamoto et al.,
2009) with the treated rats showing improved bone density.
Lentinula edodes that are exposed to UV radiation contain
enhanced vitamin D2 and have a much higher calcium content than
non-irradiated mushrooms. A study in 4-week old mice fed low
calcium and a vitamin D deficient diet showed significantly
increased femur density and tibia thickness in mice fed calcium plus
vitamin D2-enhanced mushrooms, and the expression of duodenal and renal calcium transport
genes was significantly induced. The results indicated that in mice, vitamin D2 and/or calcium
derived from irradiated Lentinula edodes may improve bone mineralization directly and by
inducing the expression of calcium-absorbing genes in the duodenum and kidney (Lee et al.,
2009b). A recent randomized controlled trial has also demonstrated that the bioavailability of
vitamin D2 from vitamin D2-enhanced mushrooms via UV-B irradiation improved vitamin D
status in humans to a level similar to that of a vitamin D2 supplement (Urbain et al., 2011).

The effects of Pleurotus eryngii extracts (PEX) on bone metabolism have been studied.
PEX treatment showed an increase in the alkaline phosphatase activity of the osteoblasts
and in the osteocalcin mRNA expression from primary osteoblasts. PEX also increased
the expression of the Runx2 gene, and the secretion of osteoprotegerin from the
135
osteoblasts showed marked increases after treatment with PEX. In vivo studies, using rats
with ovariectomy-induced osteoporosis revealed that PEX alleviated the decrease in the
trabecular bone mineral density (Kim et al., 2006b). An ethanol extract of Pleurotus eryngii
has also been reported to help protect against bone loss caused by estrogen deficiency,
without having a substantial effect on the uterus (Shimizu et al., 2006). Osteoclast forming
suppressive compounds have been isolated from the mushroom Agrocybe chaxingu (Abel
et al., 2007).
It has been suggested that the mechanisms for these effects is an increasein the alkaline
phosphatase activity of osteoblasts. The cultivation of human osteosarcoma cells HOS58 in the
presence of an aqueous extract of Grifola frondosa resulted in a significant elevation of alkaline
phosphatase activity of the cells in comparison to untreated cells. In another osteoblastic cell
line (SaOS-2) cells incubated with Grifola frondosa for 21 days, showed a nearly 2-fold higher
mineralization than cells cultured with a positive control, demonstrating the activity of Grifola
frondosa extract as a bone-inducing agent (Saif et al., 2007).
Two sterols isolated from the edible mushroom Leccinum extremiorientale have been
shown to suppress the formation of osteoclasts and thereby may have some value in the
treatment of osteoporosis (Choi et al., 2010).
17.3 Summary of Osteoporosis/Bone Mineral Density

In vitro studies have reported positive effects of mushroom extracts on mineralisation of
osteoblastic cell lines. Animal studies have reported increased bone density following
consumption of mushroom extracts, while mice fed calcium plus vitamin D2-enhanced
(UV irradiated) mushrooms showed improved bone mineralization through a direct effect
on the bone, and by inducing the expression of calcium-absorbing genes in the duodenum
and kidney.
18. Effects on Rheumatoid Arthritis

A polysaccharideprotein complex, isolated from Phellinus rimosus (Berk.), significantly
increased lipid-peroxide levels in the plasma of adjuvant-induced arthritic rats. The antioxidant
136
enzymes superoxide dismutase and glutathione peroxidase were elevated in adjuvant-induced

rats, and reduced blood glutathione was decreased. Treatments with various concentrations of
the polysaccharideprotein complex modulated the alterations produced in arthritic animals in a
dose-dependent manner (Meera et al., 2009). Anti-arthritic activity of a beta-(1,3/1,6)-D-glucan
from Pleurotus ostreatus has been reported (Bauerova et al., 2009, Rovensky et al., 2011) in a
rat model which involved an immunomodulating effect on cytokine plasma levels that changed
markedly with arthritis progression.
The effects of white button mushrooms (WBM) and shiitake mushrooms (SM) on collageninduced arthritis (CIA) have been studied in 8-wk-old female dilute brown non-agouti mice.
Compared to the control diet, WBM and SM tended to reduce the CIA index from 5.11 +/0.82 to 3.15 +/- 0.95 (P = 0.06) (median, 6-9 to 1-2) 31 d post-collagen injection.
Whereas 58% of control mice had a CIA index 7, only 23% of WBM and 29% of SM mice
did (P = 0.1). Although both types of mushrooms reduced plasma TNF alpha (34%, WBM;
64%, SM), only SM increased plasma IL-6 by 1.3-fold (P < 0.05) (Chandra et al., 2011a).
While these data provide some suggested benefits in this animal model, statistical
validation of these data is borderline, and further studies are needed to confirm such
effects. It should be noted however, that another study has suggested that supplementing
a mouse diet with 5% SM can result in a fatty liver (an elevation in IL-6 is also implicated
in fatty liver disease), but 15 days post withdrawal of SM, liver histology was completely
normalized. This effect of SM was not seen with WBM consumption (Chandra et al.,
2011b).
19. Effects on Wound Healing

In Sprague Dawley rats, an aqueous extract of the
culinary-medicinal lion's mane mushroom, Hericium
erinaceus (Bull.: Fr.) pers. (Aphyllophoromycetideae)
has been shown to accelerate wound healing in rats
(measured as less scar width at wound enclosure with
the healed wound containing fewer macrophages and
more collagen with angiogenesis, compared to wounds dressed with sterilized distilled
H2O (Abdulla et al., 2011).
137
Impaired wound healing in diabetes mellitus is a major clinical problem. Wound closure in
streptozotocin-induced diabetic rats has been shown to be significantly accelerated by oral
administration of Sparassis crispa (SC) a mushroom with a -glucan content of more than
40%, via a mechanism that may involve an increase in the migration of macrophages and
fibroblasts, with beta-glucan from SC directly increasing the synthesis of type I collagen
(Kwon et al., 2009).
Administration of Lentinus edodes polysaccharide significantly raised activities of serum
antioxidant enzymes and decreased levels of serum, mucosal interleukin-2 (IL-2) and
TNF- in rats with oral ulceration, suggesting that Lentinus edodes polysaccharide may
play a part in ameliorating oral ulceration (Yu et al., 2009c).
Polysaccharide fractions from Ganoderma lucidum have also been shown to have an
active component with healing efficacy on acetic acid-induced ulcers in the rat, which may
represent a useful preparation for studies on the prevention and treatment of peptic ulcers
(Gao et al., 2004). Pretreatment with Hericium erinaceus (Bull.: Fr.) Pers.
(Aphyllophoromycetideae) has also been shown to reduce ulceration in ethanol-induced
gastric ulcers in rats (Mahmood et al., 2008).
Oral feeding of Lentinus squarrosulus extract (250 mg/kg) offered significant gastric
mucosal protection of Sprague-Dawley rats compared to cimetidine (50 mg/kg). The ulcer
healing rate of ulcerated rats after 24, 48, and 72 hours of treatment was 82%, 90%, and
100%, respectively. The IL-1 beta level in the serum and the NF-kappa B level in the
tissues indicate that the healing potential was associated with attenuation of
proinflammatory cytokines (Omar et al., 2011). An ethanol extract of Ganoderma lucidum
(Fr.) P. Karst, at oral doses of 500 mg/kg and 1000 mg/kg has also been shown to
attenuate Indomethacin-induced gastric ulceration in rats (Rony et al., 2011).

The edible mushroom lectin from Agaricus bisporus has been reported to have antiproliferative effects on a range of cell types. A study has been undertaken to determine
whether it might have inhibitory activity on Tenon's capsule fibroblasts in in vitro models of
wound healing and therefore have a use in the modification of scar formation after
glaucoma surgery. Human ocular fibroblasts in monolayers and in three-dimensional
collagen lattices were exposed to Agaricus bisporus (0-100 g/ml). Agaricus bisporus
138
caused a dose-dependent inhibition of proliferation and lattice contraction without

significant toxicity. The data showed that Agaricus bisporus possesses key features
required of an agent that might control scarring processes and suggest that Agaricus
bisporus may be especially useful where subtle modification of healing may be needed
although further studies are required (Batterbury et al., 2002).
A dose-dependent inhibition of proliferation and lattice contraction without significant
toxicity in an in vitro model of wound healing (human ocular fibroblasts in monolayers and
in three-dimensional collagen lattices) by Agaricus bisporus (0-100 mg/ml) has been
shown (Batterbury et al., 2002), while Hericium erinaceus (Bull.: Fr.) Pers.
(Aphyllophoromycetideae) (Mahmood et al., 2008), and polysaccharide fractions from
both Ganoderma lucidum (Gao et al., 2004) and Lentinus edodes (Yu et al., 2009c) have
demonstrated efficacy in treatment of ulceration in rats via mechanisms which involved
raised activities of serum antioxidant enzymes and decreased levels of serum, mucosal
interleukin-2 (IL-2) and TNF- (Yu et al., 2009c).
20. Protective Effects Against UV-Light

The photo-protective potential of exoploysaccharides (EPS)
from Grifola frondosa HB0071 has been tested in human
dermal fibroblasts (HDF) exposed to ultraviolet-A (UVA)
light. It was reported that EPS had an inhibitory effect on
human interstitial collagenase (matrix metalloproteinase,
MMP-1) expression in UVA-irradiated HDF without any
significant cytotoxicity. The treatment of UVA-irradiated HDF
with EPS resulted in a dose-dependent decrease in the
expression level of MMP-1 mRNA. The data suggested that EPS obtained from a mycelial
culture of G. frondosa HB0071 may contribute to an inhibitory action in photo-ageing skin
by reducing the MMP 1-related matrix degradation system (Bae et al., 2005).
The anti-mutagenic effect of the mushrooms Lentinula edodes and Agaricus blazei have
been studied on conidia of Aspergillus nidulans when exposed to short wave ultraviolet
(UV) light. The data demonstrated a radio-protective and anti-mutagenic effect of L.
139
edodes and A. blazei mushrooms on eukaryotic cells when exposed to UV radiation

(Souza-Paccola et al., 2004).
21. Hypersensitivity to Mushrooms in Humans

A recent individual case study has reported
hypersensitivity pneumonitis induced by Shiitake
mushroom spores in a worker involved in mushroom
production (Ampere et al., 2012). Pulmonary function
tests showed a mild restrictive pattern, Chest CT scan
revealed reticulo-nodular shadows, slight ground glass
opacities, liner atelectasis, and subpleural opacities in
both lung fields. Serum precipitins to the Shiitake mushroom spores were positive. The
diagnosis of hypersensitivity pneumonitis due to inhalation of Shiitake mushroom spores was
established as a result of the improvement of all of the clinical symptoms of the patient, i.e.,
cough, weight loss, bilateral fine crackles, mild restrictive pattern of pulmonary function, and
reticulo-nodular shadows on chest CT, once exposure was eliminated.
Spores of Pleurotus pulmonarius, a species of Oyster mushroom, are airborne
components and established as causes of respiratory allergies. A study has shown that
spores of the oyster mushroom P. pulmonarius can induce delayed-type reactions
consistent with an acute eczema in atopic individuals, particularly in those with atopic
dermatitis (Fischer et al., 2002).
A case of mucoid impaction of the bronchi due to a hypersensitivity reaction to the
monokaryotic mycelium of Schizophyllum commune has been reported. The patient was
hospitalized because of mild asthma attacks, persistent cough, peripheral eosinophilia,
and "gloved finger" shadows on a chest roentgenogram. Cultures of the mucous plugs
and sputum samples yielded white, felt-like mycelial colonies that were later identified as
the monokaryotic mycelium of S. commune. Bronchoscopies were effective in removing
the mucous plugs and relieving the patient's symptoms (Amitani et al., 1996).
Low trehalase activity in a small number of patients has been reported to be associated
with abdominal symptoms caused by edible mushrooms. Trehalose maldigestion can
cause symptoms similar to those of lactose maldigestion and intolerance (Arola et al.,
140
1999). A recent study has also described a mushroom intolerance in some patients with
Crohns disease (Petermann et al., 2009).
A study has been conducted with 10 people where each participant ingested 4g of
Shiitake powder daily for 10 weeks (trial 1), and the protocol was repeated in the same
subjects after 3 to 6 months (trial 2). Gastrointestinal symptoms coincided with
eosinophilia in two subjects. Symptoms and eosinophilia resolved after discontinuing
Shiitake ingestion. The authors reported that daily ingestion of Shiitake mushroom powder
in five of 10 healthy persons provoked blood eosinophilia, increased eosinophil granule
proteins in serum and stool, and increased gastrointestinal symptoms (Levy et al., 1998).
Shiitake dermatitis after the ingestion of raw Shiitake mushrooms has been reported,
primarily in Japan, and it has been suggested that this dermatitis may be photosensitive
as nearly half of the patients studied developed the dermatitis on skin exposed to sunlight
(Hanada and Hashimoto, 1998). A study in Korea has also reported dermatitis effects, but
contrary to the previous reports in Japan, cases with Shiitake dermatitis occurred after
eating boiled or cooked Shiitake mushrooms suggesting that a non-thermolabile
factor/component may be involved (Ha et al., 2003).
Skin and respiratory symptoms developed within 2 months of exposure in a patient
involved in the commercial production of Shiitake mushrooms. A diagnosis of contact
urticaria and allergic contact dermatitis from Shiitake mushrooms was confirmed by prick
and patch tests. The respiratory symptoms, their timing, the presence of precipitating IgG
antibodies to Shiitake spores and increased amounts of inflammatory cells and T
lymphocytes in bronchoalveolar lavage indicated allergic alveolitis (mushroom worker's
disease) (Tarvainen et al., 1991).
Hypersensitivity pneumonitis induced by Pleurotus eryngii spores has been reported in a
worker in an Eringi (Pleurotus eryngii) mushroom factory who had worked there for 6
years. Chest radiography showed diffuse fine nodular shadows. Chest computed
tomography demonstrated centrilobular nodules and increased attenuation in both lungs.
The patient suffered from hypoxemia while breathing room air. The lymphocyte count in
the bronchoalveolar lavage fluid was increased, and transbronchial lung biopsy
specimens showed lymphocyte alveolitis with epithelioid cell granulomas in the alveolar
spaces. After admission, the patient's symptoms improved rapidly without medication.
However, on his return to work, fever and hypoxemia appeared again. The lymphocyte
stimulating test was positive against extracts of Eringi spores. Precipitins against the
141
extracts of Eringi spores were detected by the double immunodiffusion test. The diagnosis
was hypersensitivity pneumonitis (HP) caused by Eringi spores. In Japan, more than 30
cases of HP induced by mushroom spores have been reported and therefore this is an
occupational health and safety issue, related to air quality in mushroom factories that
needs to be addressed. The symptoms appear to improve rapidly without medication
(Miyazaki et al., 2003).
Chronic hypersensitivity pneumonitis induced by Lentinula edodes (Shiitake) mushrooms
in long-term mushroom industry workers appears to be characterised by a tendency
toward increasing lymphocytes and high CD4/CD8 ratio in bronchoalveolar lavage fluids.
Treatment with steroids seems to have a limited effect, while avoidance of the antigen is
important (Kai et al., 2008).
Hypersensitivity pneumonitis in a mushroom industry worker due to Pholiota nameko
spores has been reported (Nakazawa and Tochigi, 1989), and hypersensitivity
pneumonitis to spores of Pholiota nameko has been reported in a mushroom farmer,
although separation from the antigen along with corticosteroid therapy, resulted in the
symptoms and inflammatory effects quickly subsiding (Inage et al., 1996).
Bunashimeji-related hypersensitivity pneumonitis has been reported in workers who
cultivate this mushroom in indoor facilities. An evaluation of protective measures
concluded that complete cessation was the best treatment for hypersensitivity
pneumonitis. The use of a mask was ineffective for patients with a high serum Krebs von
der Lungen-6 (KL-6), surfactant protein-D (SP-D) concentration and severe ground-glass
opacity on chest high-resolution computed tomography. Initial treatment with oral
prednisolone was recommended for patients with high levels of total cell counts in
bronchoalveolar lavage fluid (Tsushima et al., 2006).
Occupational hypersensitivity pneumonitis (HP) caused by Grifola frondosa (Maitake)
mushroom spore has been successfully treated with an extra-fine aerosol corticosteroid;
beclomethasone dipropionate (BDP) dissolved in hydrofluoroalkane-134a (HFA)(Tanaka
et al., 2004).
142
21.1 Summary of Hypersensitivity Studies

Spores of mushrooms are airborne components and can be the cause of hypersensitivity /
respiratory allergy. The small number of cases reported, primarily in Japan, usually
involve workers in the commercial production of mushrooms, where air-quality may be
poor, and hence this condition has been referred to as mushroom workers disease. The
symptoms for this condition usually improve rapidly, either without medication, when the
affected person is removed from the factory environment, or after corticosteroid
administration via a nasal spray.
22. Food Safety Studies

A Phase I Clinical Trial of the dietary
supplement, Agaricus blazei Murill (ABM), in
cancer patients in remission has recently been
completed. Cancer survivors took 1.8, 3.6, or
5.4 g ABM granulated powder per day orally for
6 months. Seventy-eight patients were
assessed for safety of ABM (30/24/24 subjects
at 1/2/3 packs per day, respectively). Adverse
events were observed in 9 patients (12%), with most being digestive in nature such as nausea
and diarrhoea, and one patient developed a liver dysfunction-related food allergy, drug
lymphocyte product. However, none of the adverse events occurred in a dose-dependent
manner. The study showed that ABM does not cause problems in most patients within
laboratory parameters at the dosages tested over 6 months, supporting previous studies that
the ABM product is generally safe, excluding possible allergic reaction (Ohno et al., 2011).
The European Food Safety Authority (EFSA) has recently carried out a safety assessment for
Lentinex, an aqueous mycelial extract of Lentinula edodes (Shiitake mushroom), as a novel
food ingredient in the context of Regulation (EC) No 258/97. Lentinex consists of
approximately 98 % water and 2 % dry matter (beta-glucan lentinan, free glucose and Ncontaining constituents). The proposed intake of 2.5 mL Lentinex containing 1 mg lentinan
(beta-glucan)/mL corresponds to 41.7 mug/kg body weight for a 60 kg person. The intake of
beta-glucan resulting from the proposed use is low compared to the intake estimated from the
143
consumption of the mushroom Lentinula edodes and of other beta-glucan sources. The
animal and human studies provided by the applicant to EFSA were primarily carried out to
determine the efficacy of the novel food ingredient; they were supporting but of limited value
regarding a safety assessment. Owing to the fermentative production of the novel food
ingredient from the mycelium and the final application of a heat-induced sterilisation step in
various food products, adverse effects reported after the consumption of the fruiting body of
the Shiitake mushroom were not considered relevant. Although an allergenic risk cannot be
excluded for sensitive subjects, EFSA concluded that such a risk was expected not to be
higher than that resulting from the normal consumption of the fruiting body of Lentinula
edodes. EFSA noted the presence of soy peptides in the culture medium. The safety of
Lentinex as a novel food ingredient was established at the proposed conditions of use and the
proposed levels of intake (EFSA Panel on Dietetic Products and Allergies, 2010).
An issue regarding significant amounts of nicotine in dried wild mushrooms (mainly Boletus
edulis from China) was reported to the European Commission which resulted in the European
Food Safety Authority (EFSA) proposing temporary maximum residue levels of 0.036 mg/kg
for fresh wild mushrooms and 1.17 mg/kg for dried wild mushrooms (2.3 mg/kg for dried ceps
only). The EFSA also highlighted the necessity for a monitoring and testing programme to be
launched by food business operators at the start of the 2009 harvest season. An LC-MS/MS
system has been described and validated that provides a quick and sensitive analytical
method for routine analysis of nicotine in fresh and dried mushrooms (Cavalieri et al., 2010).
A double-blind, placebo-controlled, cross-over intervention study has investigated the
effects of 4 weeks Lingzhi (Ganoderma lucidum) supplementation on a range of
biomarkers for antioxidant status, cardiovascular disease (CHD) risk, DNA damage,
immune status, and inflammation, as well as markers of liver and renal toxicity. The study
was performed as a follow-up to a study that showed that antioxidant power in plasma
increased after Lingzhi ingestion, and that 10 day supplementation was associated with a
trend towards an improved CHD biomarker profile. Fasting blood and urine from healthy,
consenting adults (n=18; aged 22-52 years) was collected before and after 4 weeks
supplementation with a commercially available encapsulated Lingzhi preparation (1.44g
Lingzhi/d; equivalent to 13.2g fresh mushroom/d) or placebo. No significant change in any
of the variables was found, although a slight trend toward lower lipids was seen, and
antioxidant capacity in urine increased. The results showed no evidence of liver, renal or
DNA toxicity with Lingzhi intake (Wachtel-Galor et al., 2004).
Ukawa and colleagues (Ukawa et al., 2007) have described the oral administration of
144
Lyophyllum decastes Sing.(Hatakeshimeji) to adults (n=11) for two weeks, during which
the authors assessed blood tests, urine tests, blood pressure and body measurement
checks. There were no clinical problems observed with regard to blood test results,
hepatic and renal functions, glucose and lipid metabolisms, and blood pressure. Similarly,
analysis of agaritine from hot-water extracts of Hatakeshimeji showed no clinical effects
suggesting that the extract of Hatakeshimeji was a safe food product.
22.1 Animal Model Studies

The toxicological safety of an extract from cultured Lentinula edodes mycelia (L.E.M.) has
been determined using repeated doses (2,000 mg/kg/day) to male and female Wistar rats for
28 days. No mortality or abnormality in the general status or appearance was observed in rats
administered L.E.M extract. The study reported no clinically significant changes related to
toxicity. The no observed adverse effect level (NOAEL) of L.E.M. extract was considered to be
more than 2,000 mg/kg/day (Yoshioka et al., 2010).
Active Hexose Correlated Compound (AHCC), a mushroom extract rich in alpha-1,4 linked
glucans, is used in Japan as a dietary supplement to boost immune function. A series of
toxicological studies were conducted on a freeze dried preparation of AHCC (AHCC-FD).
AHCC-FD was not mutagenic to Salmonella Typhimurium and did not exhibit clastogenicity in
a mouse micronucleus assay. In a 90-day study, Sprague-Dawley rats were administered
1000, 3000, or 6000mg/kg body weight/day by gavage, and no changes attributable to AHCCFD treatment were observed in overall condition, body weight, food consumption,
ophthalmology findings, hematology and clinical chemistry parameters, and absolute and
relative organ weights. Changes in urinary pH values observed in high-dose animals and middose females were considered physiological rather than adverse effects given the acidic
nature of AHCC-FD. Urinary protein also was increased in the same dose groups, but as this
finding was associated with decreased urinary pH and no evidence of kidney dysfunction was
observed, it was considered of no toxicological significance. Histopathological changes related
to AHCC-FD administration were observed in the limiting ridge of the stomach and in the liver
of the high-dose group. The no observed-adverse-effect level (NOAEL) was considered to
be 3000mg/kg body weight/day (Fujii et al., 2011). The effects of AHCC from Lentinula
edodes and its use as a complementary therapy in patients with cancer has recently been
reviewed (Shah et al., 2011).
145
Beta-glucan, a polymer of beta-(1,3/1,6)-glucan in mushrooms, has been assess for safety for
use as a dietary supplement and food ingredient. Sub-chronic toxicity and mutagenicity
studies were conducted Sprague Dawley rats. In the sub-chronic toxicity study, 12
rats/sex/group) were administered (gavage) mushroom beta-glucan at dose levels of 0, 500,
1000 and 2000 mg/kg body weight (bw)/day for 90 days. Administration of beta-glucan did not
result in any toxicologically significant treatment-related changes in clinical observations,
ophthalmic examinations, body weights, body weight gains, feed consumption, and organ
weights compared to the control group. No adverse effects of the beta-glucan on the
hematology, serum chemistry parameters, urinalysis or terminal necropsy (gross or
histopathology findings) were noted. The results of mutagenicity studies as evaluated by gene
mutations in Salmonella Typhimurium, in vitro chromosome aberrations and in vivo
micronucleus test in mouse did not reveal any genotoxicity of beta-glucan. Based on the
subchronic study, the no observed-adverse-effect level (NOAEL) for mushroom beta-glucan
was determined to be 2000 mg/kg bw/day, the highest dose tested in the study (Chen et al.,
2011c).
Long term Agaricus bisporus consumption has been studied in rats. Female Charles River
Sprague - Dawley rats were fed a diet containing a 30% dry powder of A. bisporus for 500
days. A control group was given a basal diet without A. bisporus. There was no significant
difference in the incidence of tumours between the experimental group and control group.
No carcinogenic activity of A. bisporus was observed in this long-term study (Matsumoto
et al., 1991).
A study to evaluate the chronic toxicity and oncogenicity of Agaricus blazei Murill in F344
rats has been reported (Lee et al., 2008). Long-term (2 years) feeding of rats of a
powdered diet containing Agaricus blazei at levels up to 25,000 ppm (parts per million)
revealed no remarkable change in mean body weight, body weight gain, hematologic or
serum chemistry parameters, or absolute or relative organ weights in control or treatment
groups. Mortality in male treatment (mushroom) groups was significantly lower than in
controls. Histopathological studies showed no increased incidence of tumours.
Acute toxicity studies of a lectin from a saline extract of the fruiting bodies of the Shiitake
mushroom, Lentinula edodes (Berk). The lectin had no covalently-linked carbohydrate and
amino acid composition analysis revealed that it contained 124 amino acid residues and was
rich in tyrosine, proline, phenylalanine, arginine, glutamic acid and cysteine. LEL did not cause
mortality, nor was it observed to alter the morphology of key organs when administered
146
intraperitoneally at concentrations up to 10,000 mg/kg body weight of mice (Eghianruwa et al.,

2011).
The potential toxicity of Coriolus versicolor standardized water extract after acute and
subchronic administration in rats has been studied. In the acute toxicity study, Coriolus
versicolor water extract was administered by oral gavage to Sprague-Dawley (SD) rats (6
males, 6 females) at single doses of 1250, 2500 and 5000 mg/kg. In the subchronic toxicity
study, the extract was administered orally at doses of 1250, 2500 and 5000 mg/kg/day for 28
days to male and female SD rats respectively. There was no mortality or signs of toxicity in the
acute and subchronic toxicity studies under the above conditions (Hor et al., 2011).
A 90-day sub-chronic oral toxicological assessment of Antrodia cinnamomea, a medicinal
mushroom has also been recently completed in 80 Sprague-Dawley rats. Doses of 3000,
2200 and 1500 mg/kg BW/day were given for 90 consecutive days and reverse osmosis
water was used as control. All animals survived to the end of the study. During the
experiment period, no abnormal changes were observed in clinical signs, body weight and
ophthalmological examinations. No significant differences were found in urinalysis,
hematology and serum biochemistry parameters between the treatment and control
groups. Necropsy and histopathological examination indicated no treatment-related
changes. The no-observed-adverse-effect level (NOAEL) of Antrodia cinnamomea was
identified to be greater than 3000 mg/kg BW/day (the highest dose tested in this study) in
Sprague-Dawley rats (Chen Tai et al., 2011a). A further toxicological study on this
mushroom in pregnant Sprague Dawley rats concluded that this mushroom has no
teratogenic effects in female rats (Chen Tai et al., 2011b).
22.2 Agaritine
Agaritine purified from Agaricus blazei Murrill has previously
been shown to inhibit the proliferation of a number of human
leukemic cell lines (Endo et al., 2010a). A more recent study
by the same group has now shown that the mechanism by
which agaritine acts in U937 leukemic cells is via the
moderate induction of apoptosis via caspase activation
through cytochrome C release from mitochondria (Akiyama
et al., 2011).
147
Although agaritine has been described in some studies as a potential carcinogen, the
scientific validity of the experimental designs and models from which this conclusion has
been drawn have been contradicted and challenged by other studies. A review of the
available evidence has concluded that agaritine from consumption of cultivated Agaricus
bisporus mushrooms poses no known toxicological risk to healthy humans (Roupas et al.,
2010b).
23. Mushroom bioactive compounds and proposed

mechanisms
Recent studies on mushrooms and their extracts (Tables 7 and 8), have identified roles
involving host-mediated immunomodulatory responses, via stimulation of both innate and
adaptive immune pathways, with implications for inhibition of tumor growth via anti-proliferative
effects and induction of apoptosis in human cancer cells.
Polysaccharides from mushrooms, generally belonging to the -glucan family appear to inhibit
tumor growth by stimulating the immune system. Some of the more efficacious compounds in
mushrooms are 1,6-branched 1,3--glucans, which are recognised by pattern-recognition
receptors on immune cells such as monocytes, granulocytes and dendritic cells. Beta-glucans
in mushrooms are also known to exert immunomodulatory effects via activation of
macrophages, balance of T helper cell (TH1 and TH2 in particular) populations and subsequent
effects on natural killer (NK), cells and also via cytokine production (Hetland et al., 2004). In
addition to -glucans, polysaccharides with other sugar moieties such as -glucans have also
been implicated (Borchers et al. 2008) while other studies with non-medicinal mushrooms
containing 1,4-glucans have not shown similar effects suggesting that branching of the glucans may provide specificity to the binding of these compounds to immune cells. While the
majority of these mechanisms have been determined in in vitro or in vivo animal studies, some
recent data have also provided evidence for such immunomodulatory effects (increased NK cell
activity, effects on IgG, IgM, neutrophil and leukocyte counts) in humans from oral ingestion of
dietary polysaccharides (glucans) from some varieties of mushrooms (Ramberg et al, 2010),
which further strengthens this evidence.
Apoptosis and/or anti-proliferative effects on carcinomas and cell lines is a mechanism shared
by several mushrooms and their extracts in studies of anti-cancer effects. The anti-tumor
effects of proteoglycan fractions of mushrooms involve the elevation of natural killer (NK) cell
148
numbers and the stimulation of inducible NO synthase gene expression, which is then followed
by NO production in macrophages via activation of the transcription factor, NF-kappaB.
Activation of NK cells is likely via interferon-gamma and interleukin mediated pathways. In
addition to the apoptotic and anti-proliferative effects, the anti-inflammatory and anti-microbial /
viral effects outlined may also contribute to the anti-carcinogenic effects of mushrooms and
their extracts, although such direct links have not been established to date. As mentioned
above, while the majority of such mechanisms have been determined in in vitro or in vivo
animal studies, mushroom polysaccharides in particular are beginning to be evaluated as
adjuvant cancer therapy compounds alongside conventional cancer treatments (Standish et al.,
2008), particularly in breast cancer patients with estrogen receptor positive tumors where
mushroom extracts have been shown to inhibit aromatase activity (Grube et al., 2001, Chen et
al., 2006) and subsequent reduction of estrogen.
While the effects and underlying mechanisms of mushroom polysaccharides in health
outcomes have been more extensively evaluated, bioactive proteins from mushrooms (such as
lectins, fungal immunomodulatory proteins (FIP), ribosome inactivating proteins (RIP),
ribonucleases and other proteins have also been reported to possess anti-tumor, anti-viral and
immunomodulatory activities. Furthermore, ergosterol and agaritine, present in mushrooms of
the Agaricus family, have been reported to inhibit proliferation of leukemic cells without effects
on normal lymphatic cells and that this activity was distinct from that of -glucan (Endo et al.,
2010b).
149
24. Mushroom Varieties Effects on Health
Agaricus bisporus (common white button, brown / crimini,

portabella)
Secretory immunoglobulin A (sIgA) acts as the first line of

adaptive humoral immune defense at mucosal surfaces. A
randomised trial of 24 healthy volunteers has shown that
consumption of 100 g of blanched Agaricus bisporus daily
with a normal diet for 1 wk significantly accelerated sIgA
secretion, thereby indicating its effect on the improvement of
mucosal immunity (Jeong et al., 2011).
A single-blinded, randomized, placebo-controlled trial
(registered at http://germanctr.de as DRKS00000195) in 26 young subjects with serum
25-hydroxyvitamin D (25OHD) < 50 nmol/l undertaken over a 5 week period has
demonstrated the bioavailability of vitamin D2 from UV-B-irradiated button mushrooms in
healthy adults deficient in serum 25-hydroxyvitamin D. Furthermore, the bioavailability of
vitamin D2 from vitamin D2-enhanced button mushrooms via UV-B irradiation was
effective in improving vitamin D status and not different to a vitamin D2 supplement
(Urbain et al., 2011).
A recent randomised controlled trial of 38 adults consuming ergocalciferol from Agaricus
bisporus or supplements for 6 weeks has reported that ergocalciferol was absorbed and
metabolized to 25-hydroxyergocalciferol (25(OH)D2) but did not affect vitamin D status,
because 25-hydroxycholecalciferol (25(OH)D3) decreased proportionally in serum
(Stephensen et al., 2012).
Exposing white button mushrooms to ultraviolet B (UVB) light markedly increases their
vitamin D2 content. In weanling female rats, diets containing 2.5% and 5.0% light-exposed
mushrooms significantly raised 25-hydroxyvitamin D (25(OH)D) and suppressed
parathyroid hormone levels compared to control-fed rats or rats fed 5.0% mushroom
unexposed to light. Vitamin D2 from UVB-exposed mushrooms was reported to be
bioavailable, safe, and functional in supporting bone growth and mineralization in a
150
growing rat model without evidence of toxicity (Calvo et al., 2012). Enrichment of vitamin
D 2 in Agaricus bisporus white button mushroom using continuous UV light needs a
longer exposure time, which can lead to discoloration, however, exposure of whole or
sliced mushrooms to pulsed UV light significantly increased vitamin D2 without any
observed discoloration (Rao Koyyalamudi et al., 2011).
The effects of UVB on Agaricus bisporus are limited to changes in vitamin D and show no
detrimental changes relative to natural sunlight exposure. On a dry weight basis, no
significant changes in vitamin C, folate, vitamins B 6, vitamin B 5, riboflavin, niacin, amino
acids, fatty acids, ergosterol, or agaritine were observed following UVB processing, while
exposure to sunlight resulted in a 26% loss of riboflavin, evidence of folate oxidation, and
unexplained increases in ergosterol (9.5%) (Simon et al., 2011). Vitamin D2 can be
increased by UV-B exposure during the growth phase of Agaricus bisporus. Growth is
unaffected by UV-B. Post-harvest exposure to supplementary UV-B resulted in a higher
vitamin D2 content of 32 mg/100 g compared to 24 g/100 g obtained from exposure to
UV-B during the growth phase (Kristensen et al., 2012).
A comparison has been undertaken of the antioxidant properties and phenolic profile of
the most commonly consumed fresh cultivated mushrooms and their mycelia produced in
vitro: Agaricus bisporus (white and brown), Pleurotus ostreatus (oyster), Pleurotus eryngii
(king oyster) and Lentinula edodes (shiitake). Of the mushrooms evaluated, the
mushroom species with the highest antioxidant potential was Agaricus bispous (brown),
with in vitro, L. edodes possessed the highest reducing power. Generally, in vivo samples
revealed higher antioxidant properties than their mycelia obtained by in vitro techniques.
There was no correlation between the studied commercial mushrooms and the
corresponding mycelia obtained in vitro (Reis et al., 2012).
Agaricus bisporus (white button and crimini), Lentinula edodes (shiitake), Pleurotus
ostreatus (oyster), and Grifola frondosa (maitake) mushrooms have been shown to inhibit
adhesion molecule expression and in vitro binding of monocytes to human aortic
endothelial cells under pro-inflammatory conditions, which are associated with
cardiovascular disease (Martin, 2010b). A further study by the same group reported that
ergothioneine, an antioxidant present in edible mushrooms, was able to interrupt proinflammatory induction of adhesion molecule expression associated with atherogenesis,
and to inhibit monocyte binding to endothelial cells characteristic of early cardiovascular
disease (Martin, 2010a).
151
The bioavailability of ergothioneine from Agaricus bisporus, that functions as an

antioxidant in mushrooms has been determined in a pilot study in healthy men (n=10)
using a randomized, cross-over, dose-response, postprandial time-course design.
Ergothioneine was bioavailable after consuming mushrooms (8g and 16g) and a trend in
the postprandial triglyceride response indicated that there was a blunting effect after both
the 8g and 16g ergothioneine doses were compared with the control (0g dose).
Ergothioneine from A. bisporus mushrooms was therefore bioavailable as assessed by
red blood cell uptake postprandially, and consumption was associated with an attenuated
postprandial triglyceride response (Weigand-Heller et al., 2012).
Analyses of Agaricus bisporus (brown), in three flushes and at two different harvest times
showed the mean Zn, Fe, P, Mg, K, Na, and Ca contents of both harvests were 8.157.07,7.40-7.96, 1180.93-1038.69, 88.05-76.29, 213.29-238.82, 2652.0-2500.89, and
534.2-554.80 mg/kg, respectively. In terms of vitamin C, folic acid, thiamin, riboflavin, and
niacin, the mean contents were 6.75-3.97, 0.09-0.08, 0.085-0.09, 0.27-0.29, and 3.622.94 mg/kg, respectively. The estimated volatile components comprised 18- or 16-carbon
compounds such as octadecanoic acid, hexadecanoic acid derivatives, and other
important volatiles like di-limonene, n-nonane, benzendicarboxylic acid, and cis-linoleic
acid esters. (Caglarirmak, 2009).
It is of interest to note that the antioxidant (free radical-scavenging) activity reported in
ethanol extracts of Agaricus bisporus as well as the total phenolic and flavonoid
concentration are similar before and after boiling (Jagadish et al., 2009). This study also
reported antibacterial activity against both gram positive and gram negative bacteria, as
well as anticandidal activity against Candida albicans by the Agaricus bisporus extracts as
well as inhibition of cell proliferation of HL-60 leukemia via the induction of apoptosis.
Dietary intake of white button mushroom, Agaricus Bisporus has been shown to
significantly lower liver weight and hepatic injury markers in ovariectomized mice (a model
of postmenopausal women). There was less fat accumulation in the livers of mice on the
mushroom diet, and the mice had improved glucose clearance ability. Genes related to
the fatty acid biosynthesis pathway, particularly the genes for fatty acid synthetase (Fas)
and fatty acid elongase 6 ( Elovl6), were down-regulated in the liver of mushroom-fed
mice. In vitro mechanistic studies using the HepG2 cell line showed that down-regulation
of the expression of FAS and ELOVL6 by this mushroom extract was through inhibition of
152
liver X receptor (LXR) signalling and its downstream transcriptional factor SREBP1c
(Kanaya et al., 2011b).
Extracts from Agaricus bisporous mushrooms have been suggested as potential breast
cancer chemopreventive agents, as they suppress aromatase activity and estrogen
biosynthesis. A recent study has evaluated the activity of mushroom extracts in the
estrogen receptor-positive/aromatase-positive MCF-7aro cell line in vitro and in vivo.
Mushroom extract decreased testosterone-induced cell proliferation in MCF-7aro cells but
had no effect on MCF-10A, a non-tumourigenic cell line. Most potent mushroom
chemicals are soluble in ethyl acetate. The major active compounds found in the ethyl
acetate fraction were unsaturated fatty acids such as linoleic acid, linolenic acid, and
conjugated linoleic acid. The interaction of linoleic acid and conjugated linoleic acid with
aromatase mutants expressed in Chinese hamster ovary cells showed that these fatty
acids inhibited aromatase with similar potency and that mutations at the active site regions
affect its interaction with these two fatty acids. Whereas these results suggest that these
two compounds bind to the active site of aromatase, the inhibition kinetic analysis
indicated that they are non-competitive inhibitors with respect to androstenedione. As only
conjugated linoleic acid was found to inhibit the testosterone-dependent proliferation of
MCF-7aro cells, the physiologically relevant aromatase inhibitors in mushrooms are most
likely conjugated linoleic acid and its derivatives. The in vivo action of mushroom
chemicals was shown using nude mice injected with MCF-7aro cells. The studies showed
that the mushroom extract decreased both tumour cell proliferation and tumour weight
with no effect on the rate of apoptosis (Chen et al., 2006).
Two polysaccharide fractions (designated as ABP-1 and ABP-2) isolated from Agaricus
bisporus have been shown to stimulate the production of nitric oxide, interleukin-6, and
tumor necrosis factor-alpha. Modulation of macrophage function by A. bisporus
polysaccharides was mediated in part through activation of nuclear factor-kappaB. Both
ABP-1 and ABP-2 had the ability to inhibit the growth of human breast cancer MCF-7 cells
but had little effect on the growth of human colon, prostate, gastric cancer, and murine
Sarcoma 180 cells. However, when murine Sarcoma 180 cells exposed to ABP-1 or ABP2 were implanted subcutaneously into mice, a reduction in tumor growth was observed
compared with that observed in control mice. These data provide evidence that
macrophages possibly contribute to the antitumorigenic effects of Agaricus bisporus
polysaccharides (Jeong et al., 2012, Sang Chul et al., 2012). Beta-glucan-rich
polysaccharide extracts from Agaricus bisporus (but not A. blazei Murill, Phellinus linteus,
Coprinus comatus, or spores of Ganoderma lucidum) stimulated nitric oxide production by
153
bone marrow-derived macrophages. It has been suggested that branching of the betaglucan chain is essential for immune-stimulating activity (Volman et al., 2010a).
Methanol extracts from Agaricus bisporus, Boletus edulis, Cantherellus cibarius,
Cratarelluscornucopioides, Lactarius deliciosus and Pleurotus ostreatus have shown antiinflammatory activity in LPS activated RAW 264.7macrophages. A. bisporus, C. cibarius
and L.deliciosus exhibited the higher anti-inflammatory activities inducing inhibition of NO
production and iNOS, IL-1beta and IL6 mRNAs expression in response to LPS stimulation
(Moro et al., 2012).
It has been demonstrated that dietary supplementation with white button mushrooms
(Agaricus bisporus) enhances natural killer (NK) cell activity in C57BL/6 mice, suggesting
that increased intake of white button mushrooms may promote innate immunity against
tumours and viruses through the enhancement of NK activity (Wu et al., 2007a). However,
a double-blind randomized trial has been undertaken in 56 mildly hypercholesterolemic
subjects who consumed a control fruit juice with or without added alpha-glucans with the
authors suggesting that in vivo, alpha-glucans had lost their efficacy to stimulate the
immune response as observed in an in vitro mouse model (Volman et al., 2010b).
The edible mushroom lectin from Agaricus bisporus has been reported to have antiproliferative effects on a range of cell types. A study has been undertaken to determine
whether it might have inhibitory activity on Tenon's capsule fibroblasts in in vitro models of
wound healing and therefore have a use in the modification of scar formation after
glaucoma surgery. Human ocular fibroblasts in monolayers and in three-dimensional
collagen lattices were exposed to Agaricus bisporus (0-100 g/ml). Agaricus bisporus
caused a dose-dependent inhibition of proliferation and lattice contraction without
significant toxicity. The data showed that Agaricus bisporus possesses key features
required of an agent that might control scarring processes and suggest that Agaricus
bisporus may be especially useful where subtle modification of healing may be needed,
although further studies are required (Batterbury et al., 2002).
The effect on epithelial cells of a Gal beta-1,3-GalNAc-binding lectin, from the edible
mushroom Agaricus bisporus lectin (ABL) has been evaluated. ABL (25mg/ml) inhibited
incorporation of [3H]-thymidine into DNA of HT29 colon cancer cells by 87%, Caco-2 colon
cancer cells by 16%, MCF-7 breast cancer cells by 50%, and Rama-27 rat mammary
fibroblasts by 55% when these cells were grown for 24h in serum-free medium. When
assessed by cell count, similar inhibition of proliferation of HT29 cells by ABL was found.
154
ABL (0.2mg/ml) caused no cytotoxicity to HT29, MCF-7, and Rama-27 cells as measured
by trypan blue exclusion, and inhibition of proliferation in HT29 cells caused by 50mg/ml
ABL was reversible after removal of the lectin. A. bisporus lectin appears to be a
reversible non-cytotoxic inhibitor of epithelial cell proliferation which deserves further study
as a potential anti-cancer agent (Yu et al., 1993).
The reversibility of the anti-proliferative effect of Agaricus bisporus lectin is associated
with its release from cancer cells after internalization. The internalization and subsequent
slow release, with little degradation of the lectin, reflects the tendency of lectins to resist
biodegradation and implies that other endogenous or exogenous lectins may be
processed in this way by intestinal epithelial cells (Yu et al., 2000). Extracts from Agaricus
bisporus have also been shown to induce proapoptotic effects in the human leukemia cell
line K562 (Shnyreva et al., 2010).
The three-dimensional structure of the lectin from Agaricus bisporus has been determined
by x-ray diffraction. The protein is a tetramer with 222 symmetry, and each monomer
presents a novel fold with two beta sheets connected by a helix-loop-helix motif. The Tantigen disaccharide, Gal beta 1-3GalNAc, mediator of the anti-proliferative effects of the
protein, binds at a shallow depression on the surface of the molecule. The lectin has two
distinct binding sites per monomer that recognize the different configuration of a single
epimeric hydroxyl (Carrizo et al., 2005).
Aqueous extracts of the sporophores of eight mushroom species have been assessed for
their ability to prevent H2O2-induced oxidative damage to cellular DNA using the singlecell gel electrophoresis ("Comet") assay. The highest genoprotective effects were
obtained with cold (20C) and hot (100C) water extracts of Agaricus bisporus and
Ganoderma lucidum fruit bodies, respectively. These edible mushrooms therefore
represent a valuable source of biologically active compounds with potential for protecting
cellular DNA from oxidative damage (Rocha et al., 2002). A heat-labile protein has also
been identified in fruit bodies of Agaricus bisporus which protects Raji cells (a human
lymphoma cell line) against H2O2-induced oxidative damage to cellular DNA (Shi et al.,
2002).
Agaricus bisporus has been shown to lower blood glucose and cholesterol levels in
streptozotocin (STZ)-induced diabetic and rats fed a hypercholesterolemic diet (Jeong et
al., 2010). The STZ-induced diabetic male Sprague-Dawley rats fed Agaricus bisporus
powder (200 mg/kg of body weight) for 3 weeks had significantly reduced plasma glucose
155
and triglyceride concentrations (24.7% and 39.1%, respectively), liver enzyme activities,
alanine aminotransferase and aspartate aminotransferase (11.7% and 15.7%,
respectively), and liver weight gain. In hypercholesterolemic rats, oral feeding of the
Agaricus bisporus powder for 4 weeks resulted in a significant decrease in plasma total
cholesterol and low-density lipoprotein (22.8% and 33.1%, respectively). A similar
significant decrease in hepatic cholesterol and triglyceride concentrations was observed
(36.2% and 20.8%, respectively). The decreases in total cholesterol, low-density
lipoprotein, and triglyceride concentrations were accompanied by a significant increase in
plasma high-density lipoprotein concentrations demonstrating significant hypoglycemic
and hypolipidemic activity in rats.
A hypoglycemic effect on streptozotocin-induced diabetic rats has been demonstrated by
Agaricus bisporus (Sang Chul et al., 2010). Furthermore, a hot water extract of Agaricus
bisporus, administered at 400 mg/kg body weight per day for 7 days resulted in a 29.68%
reduction of serum glucose levels, with serum insulin levels significantly increasing in
streptozotocin-induced diabetic rats. However, a most interesting effect of the treatment
was the increase in cellularity of the Langerhans islets of the pancreas and their apparent
repopulation with beta cells (Yamac et al., 2010).
Lectins from Agaricus bisporus and Agaricus campestris have been shown to stimulate
insulin and glucagon release from isolated rat islets in the presence of 2 mM glucose.
Maximal stimulation of insulin release was reported at lectin concentrations above
58mg/mL (approximately 1M). The lectin did not alter islet glucose oxidation to CO2 or
incorporation of [3H] leucine into trichloracetic acid-precipitable material, nor did it modify
rates of insulin secretion induced by 20 mM glucose. None of nine other lectins tested
stimulated insulin release, whereas stimulation of fat cell glucose oxidation was a general
property of the lectins. The data also suggesting that lectin binding is essential for the
expression of insulin-releasing activity. The authors proposed that the specific interaction
between mushroom lectin and its receptors may lead to conformational changes in the
structure of the membranes of the islet A2- and B-cells that facilitate exocytosis (Ewart et
al., 1975).
Agaricus bisporus and Pleurotus sajor caju have been assayed in vitro for their antimicrobial activities using aqueous and organic solvents extracts. It has been shown that
Escherichia coli 390, Escherichia coli 739, Enterobacter aerogenes, Pseudomonas
aeruginosa and Klebsiella pneumoniae were most sensitive to aqueous, ethanol,
methanol and xylene extracts of these mushrooms (Tambekar et al., 2006).
156
A report on the fractionation of extracts of the edible mushroom, Volvariella volvacea, has
shown the isolation of two heterocyclic carboxylic acids, namely pyridine-3-carboxylic acid
[nicotinic acid] and pyrazole-3(5)-carboxylic acid and four steroidal metabolites ergosterol,
5-dihydroergosterol, ergosterol peroxide, and cerevisterol. In light of the structural
similarity of pyrazole-3(5)-carboxylic acid to pyrazole-3-carboxylic acids, which act as
agonists for nicotinic acid receptors, the levels of pyridine-3-carboxylic acid and pyrazole3(5)-carboxylic acid were estimated in V. volvacea and two other edible mushrooms,
namely Agaricus bisporus and Calocybe indica. Significant levels of pyridine-3-carboxylic
acid (nicotinic acid) were found in C. indica, and pyrazole-3(5)-carboxylic acid was found
in abundance in A. bisporus. Correlations have been suggested between the occurrence
of these compounds in mushrooms and consumption as well as beneficial health effects
(Mallavadhani et al., 2006).
mushroom (Agaricus bisporus) fiber. The results demonstrated that mushroom fiber (and
sugar beet fiber) lowered the serum total cholesterol level by enhancement of the hepatic
low density lipoprotein (LDL) receptor mRNA (Fukushima et al., 2000). Similar cholesterollowering effects in rats of Maitake (Grifola frondosa) fiber, Shiitake (Lentinus edodes)
fiber, and Enokitake (Flammulina velutipes) fiber have also been reported (Fukushima et
al., 2001).
Long term Agaricus bisporus consumption has been studied in rats. Female Charles River
Sprague - Dawley rats were fed a diet containing a 30% dry powder of A. bisporus for 500
days. A control group was given a basal diet without A. bisporus. There was no significant
difference in the incidence of tumours between the experimental group and control group.
No carcinogenic activity of A. bisporus was observed in this long-term study (Matsumoto
et al., 1991).
A study by Toth and co-workers in which Agaricus bisporus, baked at 220-230C for 10
minutes and subsequently fed to mice for 12h each day, five days each week throughout
their life and also fed a well-balanced semi-synthetic diet for 12h each day for five days
and for the remaining two full days each week, showed no statistically significant
difference in tumours in the lungs, blood vessels, cecum, and colon when compared to the
untreated controls. The estimated average daily mushroom consumption per animal was
4.8g for female mice and 4.2g for male mice (Toth et al., 1997), which exceeds the
average daily consumption of mushrooms by humans (Shephard et al., 1995).
157
Lectins from Agaricus bisporus, Phaseolus vulgaris, Momordica charantia, Ricinus

communis and its constituent chains have been shown to inhibit human immunodeficiency
virus type 1 (HIV-1) reverse transcriptase (Wang and Ng, 2001), while phenolic
compounds present in extracts from A. bisporus strongly generated reactive oxygen
species (suggesting immunomodulatory effects) in human PBMCs and K 562 cells in vitro
(Wei et al., 2008).
effects.
Agaricus blazei
A Phase I Clinical Trial of the dietary supplement, Agaricus

blazei Murill (ABM), in cancer patients in remission has
recently been completed. Cancer survivors took 1.8, 3.6, or
5.4 g ABM granulated powder per day orally for 6 months.
Seventy-eight patients were assessed for safety of ABM
(30/24/24 subjects at 1/2/3 packs per day, respectively).
Adverse events were observed in 9 patients (12%), with
most being digestive in nature such as nausea and diarrhoea, and one patient developed a
liver dysfunction-related food allergy, drug lymphocyte product. However, none of the adverse
events occurred in a dose-dependent manner. The study showed that ABM does not cause
problems in most patients within laboratory parameters at the dosages tested over 6 months,
supporting previous studies that the ABM product is generally safe, excluding possible allergic
reaction (Ohno et al., 2011).
158
A randomized, double-blind, placebo-controlled trial has evaluated the effects of Agaricus

blazei Murrill intake (900 mg/day for 60 days) on serum levels of interleukin-6 (IL-6),
interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) in 57
community-living elderly women. After 60 days, no changes from baseline were
detectable for any parameter in either the placebo (n=29) or the mushroom (n=28) group
(Lima et al., 2012).
An extract (AndoSan) from Agaricus blazei Murill (AbM) has been shown to reduce blood
cytokine levels in healthy volunteers after 12 days of ingestion, pointing to an antiinflammatory effect. This extract also modulated cytokines in patients with ulcerative colitis
(UC, n=10) and Crohn's disease (CD, n=11) in which baseline concentrations for the (17)
cytokines ebaluated in the UC and CD patient groups were largely similar. Faecal
calprotectin (a marker for inflammatory bowel disease (IBD) was reduced in the UC group.
Ingestion of an AbM-based medicinal mushroom by patients with IBD resulted in
decreased levels of pathogenic cytokines in blood and calprotectin in faeces, suggesting
anti-inflammatory effects (Forland et al., 2011). The mechanisms for such effects are
unclear, although an in vitro study by the same authors with monocyte-derived dendritic
cells showed that AbM did not induce increased synthesis of Th2 or anti-inflammatory
cytokines or the Th1 cytokine IL-12. but the AbM-based extract resulted in increased
production of proinflammatory, chemotactic and some Th1-type cytokines (Forland et al.,
2010).
A 6 month open-label study in 51 patients with prostate cancer that ingested either
Senseiro, containing extracts from the Agaricus blazei Murill mushroom, or Rokkaku
Reishi, containing the Ganoderma lucidum mushroom has reported no serious adverse
effects, and no significant anticancer effects were observed with the intake of these two
mushroom supplements (Yoshimura et al., 2010) .
A randomized, double-blinded, and placebo-controlled clinical trial has evaluated the
effects of Agaricus blazei Murill in combination with metformin and gliclazide on insulin
resistance in type 2 diabetes. Supplementation of Agaricus blazei Murill extract improved
insulin resistance among subjects with type 2 diabetes. The increase in adiponectin
concentration after taking Agaricus blazei Murill extract for 12 weeks may be the
mechanism that results in the observed effect (Hsu et al., 2007).
159
Clinical effects and safety evaluation of Agaricus Blazei Condensed Liquid (Agaricus
Mushroom Extract; ABCL) on human volunteers with C-type hepatitis has been studied. A
total of 20 patients (10 male, 10 female) with chronic C-type hepatitis received the ABCL
orally twice per day for 8 weeks. No toxicological effects, nor other side effects were
observed (Inuzuka and Yoshida, 2002).
The effects of protein-bound polysaccharides (A-PBP and L-PBP), extracted from the
mycelia of Agaricus blazei and Lentinus edodes, on serum cholesterol and body weight
have been investigated in 90 female volunteers. The data demonstrated a weightcontrolling and hypolipidemic effect of both A-PBP and L-PBP via a mechanism involving
absorption of cholesterol (Kweon et al., 2002).
The effect of Agaricus blazei Murill (AbM) on the release of several cytokines in human
whole blood both after stimulation ex vivo and in vivo after oral intake over several days
has been studied in healthy volunteers (Johnson et al., 2009). After stimulation of whole
blood ex vivo with 0.5-5.0% of a mushroom extract, mainly containing AbM, there was a
dose-dependent increase in all the cytokines studied, ranging from two to 399-fold (TNFalpha). However, in vivo in the eight volunteers who completed the daily intake (60 ml) of
this AbM extract for 12 days, a significant reduction was observed in levels of IL-1-beta
(97%), TNF-alpha (84%), IL-17 (50%) and IL-2 (46%). Another nine cytokines were
measured but they were unaltered. The discrepant results on cytokine release ex vivo and
in vivo may partly be explained by the antioxidant activity of AbM in vivo and limited
absorption of its large beta-glucans across the intestinal mucosa to the reticuloendothelial
system and blood.
Agaritine purified from Agaricus blazei Murrill has been shown to exert anti-tumour activity
against leukemic cells (Endo et al., 2010b). In this study, a hot water extract of Agaricus
blazei Murrill (ABM) powder was fractionated by HPLC based on the anti-tumour activity
against leukemic cells in vitro. The purified substance was identified as agaritine, beta-N(gamma-l(+)-glutamyl)-4-(hydroxymethyl) phenylhydrazine, having a molecular mass of
267Da. This compound inhibited the proliferation of leukemic cell lines such as U937,
MOLT4, HL60 and K562, but showed no significant effect on normal lymphatic cells. The
authors concluded that agaritine has direct anti-tumour activity against leukemic tumor
cells in vitro which is in contrast to the carcinogenic activity previously ascribed to this
compound. The data also showed that this activity was distinct from that of beta-glucan,
which indirectly suppresses proliferation of tumour cells.
160
In general, the anti-tumour activity of Agaricus blazei appears to be mainly due to the
activation of the immune system rather than to any direct effects on tumour cells. This is
supported by the fact that macrophages derived from rat bone marrow have been shown
to be activated and cytokines such as tumour necrosis factor-alpha (TNF-), interleukin-1
(IL-1) and IL-8, and nitric oxide (NO) were secreted, in response to water extracts in in
vitro experiments. Furthermore, oral administration of Agaricus blazei water extracts to
mice has been shown to induce the activation of macrophages and T cells in vivo. Antigenotoxic, anti-mutagenic and anti-clastogenic effects have also been detected in
Agaricus blazei water extracts (Sorimachi and Koge, 2008). Agaricus blazei Murrill
extracts, under certain conditions, have also been shown to have anti-mutagenic activities
in mice that may contribute to an anti-carcinogenic effect (Delmanto et al., 2001).
Oral administration of dried fruiting bodies of A. blazei has been shown to augment
cytotoxicity of natural killer (NK) cells in wild-type (WT) C57BL/6, C3H/HeJ, and BALB/c
mice. Augmented cytotoxicity was demonstrated by purified NK cells from treated wildtype (WT) and RAG-2-deficient mice, but not from interferon-gamma (IFN-gamma)
deficient mice. NK cell activation and IFN-gamma production was also observed in vitro
when dendritic cell (DC)-rich splenocytes of WT mice were coincubated with an extract of
A. blazei. Both parameters were largely inhibited by neutralizing anti-interleukin-12 (IL-12)
monoclonal antibody (mAb) and completely inhibited when anti-IL-12 mAb and anti-IL-18
mAb were used in combination. An aqueous extract of the hemicellulase-digested
compound of A. blazei particle (ABPC) induced IFN-gamma production more effectively,
and this was completely inhibited by anti-IL-12 mAb alone. NK cell cytotoxicty was
augmented with the same extracts, again in an IL-12 and IFN-gamma-dependent manner.
These results demonstrate that A. blazei and ABPC augmented NK cell activation through
IL-12-mediated IFN-gamma production (Yuminamochi et al., 2007).
Aqueous extracts of Agaricus blazei fruiting body prepared at different temperatures have
been fractionated by ethanol precipitation with various ethanol concentrations. The
original aqueous extracts of A. blazei failed to stimulate natural killer (NK) cell activity in
murine spleen cells in vitro, but the strongest effect was observed in a 30% ethanolsoluble-50% ethanol-insoluble fraction prepared from the extract at 40C (fraction A-50).
Fraction A-50 also showed the strongest augmenting effect on interferon (IFN)-gamma
production. This augmentation of NK activity and IFN-gamma production by fraction A-50
was completely abrogated by heat treatment (Zhong et al., 2005).
Polysaccharide fractions of Agaricus blazei have been prepared from cultured A. blazei by
161
repeated extraction with hot water (AgHWE), cold NaOH (AgCA), and then hot NaOH
(AgHA). By chemical, enzymic, and NMR analyses, the primary structures of AgHWE,
AgCA, and AgHA were mainly composed of 1,6-beta-glucan. Among these fractions, the
NaOH extracts showed anti-tumour activity against the solid form of Sarcoma 180 in ICR
mice. To demonstrate the active component in these fractions, several chemical and
enzymic treatments were applied. These fractions were found to be i) neutral beta-glucan
passing DEAE-Sephadex A-25, ii) resistant to periodate oxidation (I/B) and subsequent
partial acid hydrolysis (I/B/H), iii) resistant to a 1,3-beta-glucanase, zymolyase, before I/B,
but sensitive after I/B/H. In addition, after I/B/H treatment of the neutral fraction of AgCAE,
a signal around 86 ppm attributable to 1,3-beta glucosidic linkage was detectable in the
13
C-NMR spectrum. These data strongly suggest that a highly branched 1,3-beta-glucan
segment forms the active centre of the anti-tumour activity (Ohno et al., 2001).
Agaricus blazei Murill has been reported to possess biological effects that include
immunomodulatory activities, although the number of in vivo studies is limited. A recent
study has evaluated the immunomodulatory effects of A. blazei in 160 male Balb/cByJ
mice. The mice were divided into four groups and treated with various quantities of
intragastric A. blazei extract or distilled water for 8 to 10 weeks. Nine parameters, relating
to general immune function or adaptive immunity against immunogen chicken ovalbumin,
were determined. The mice receiving A. blazei extract exhibited significantly greater
serum immunoglobulin G levels, increased T-cell numbers in spleen, and elevated
phagocytic capability compared with controls. Consumption of A. blazei was also
associated with significant increases in ovalbumin-specific serum immunoglobulin G level,
delayed-type hypersensitivity, splenocyte proliferation rate, and tumour necrosis factoralpha secretion by splenocytes, indicating that A. blazei Murill possesses a wide range of
immunomodulatory effects in vivo (Chan et al., 2007). Agaricus blazei has also been
reported to have inhibitory effects on mast cell-mediated anaphylaxis-like reactions (Choi
et al., 2006b).
Beta-glucans and and their enzymatically hydrolyzed oligosaccharides from Agaricus
blazei have anti-hyperglycemic, anti-hypertriglyceridemic, anti-hypercholesterolemic, and
anti-arteriosclerotic activity indicating overall anti-diabetic activity in diabetic rats.
However, the enzymatically hydrolyzed oligosaccharides have been shown to have
around twice the activity of beta-glucans with respect to anti-diabetogenic activity (Kim et
al., 2005b).
Beta-glucans from Agaricus blazei have also been reported to not exert a genotoxic or
162
mutagenic effect, but that it does protect against DNA damage caused by benzo[a]pyrene
in the human hepatoma cell line HepG2. The data suggest that beta-glucan acts through
binding to benzo[a]pyrene or the capture of free radicals produced during its activation
(Angeli et al., 2009).
Extracts from Agaricus blazei Murill (AbM) have been evaluated on changes to gene
expression on a human monocyte cell line (THP-1). Changes in the levels of mRNA
transcripts were measured using 35 k microarrays, and the changes in select cytokine
gene products by immunoassays. Lipopolysaccharide (LPS) was included for comparison.
Both AbM and LPS had very significant effects on gene expression. Genes related to
immune function were selectively up-regulated, particularly pro-inflammatory genes such
as the interleukins IL1B and IL8. Although most genes induced by AbM were also induced
by LPS, AbM produced a unique profile, e.g., as to a particular increase in mRNA for the
cytokines IL1A, CXCL1, CXCL2 and CXCL3, as well as PTGS2 (cyclooxygenase2)
(Ellertsen et al., 2006).
An extract from Agaricus blazei Murill Kyowa (ABMK), has been reported to possess antimutagenic and anti-tumour effects. A study has investigated the effects of ABMK
consumption on immunological status and quality of life in cancer patients undergoing
chemotherapy. One hundred cervical, ovarian, and endometrial cancer patients were
treated either with carboplatin (300mg/m2) plus VP16 (etoposide, 100mg/m2) or with
carboplatin (300mg/m2) plus taxol (175mg/m2) every 3 weeks for at least three cycles, with
or without oral consumption of ABMK. The authors observed that natural killer cell activity
was significantly higher in the ABMK-treated group compared to the non-treated placebo
group (n = 61). However, no significant difference in lymphokine-activated killer and
monocyte activities was observed in a manner similar to the count of specific immune cell
populations between ABMK-treated and non-treated groups. However, chemotherapyassociated side effects such as appetite, alopecia, emotional stability, and general
weakness were all reported to be improved by ABMK treatment, with the authors
suggesting that ABMK treatment may have some beneficial effects for gynecological
cancer patients undergoing chemotherapy (Ahn et al., 2004).
The effects of Agaricus blazei Murill on the growth of human prostate cancer have been
examined in vitro and in vivo. A. blazei, particularly in a broth fraction, inhibited cell
proliferation in both androgen-dependent and androgen-independent prostate cancer cell
lines. The broth of A. blazei induced lactate dehydrogenase leakage in three cancer cell
lines, whereas the activities of caspase 3 and the DNA fragmentation were enhanced the
163
most in androgen-independent PC3 cells. Oral supplementation with the broth of A. blazei
(with the higher ratio of beta-glucan) significantly suppressed tumour growth without
inducing adverse effects in severe combined immunodeficient mice with PC3 tumor
xenograft. The data suggested that the broth of A. blazei may directly inhibit the growth of
prostate cancer cell via an apoptotic pathway and suppress prostate tumour growth via
antiproliferative and antiangiogenic mechanisms (Yu et al., 2009a).
The efficacy and safety of Senseiro (containing extracts from Agaricus blazei Murill) and
Rokkaku Reishi, (containing the Ganoderma lucidum mushroom) have been evaluated
over 6 months in patients with prostate cancer in Japan (Yoshimura et al., 2010). Patients
with biochemical failure after radical treatment for non-metastasized prostate cancer were
enrolled in this open-label study. No partial response in terms of serum prostate-specific
antigen was observed. Alteration of serum prostate-specific antigen doubling time did not
correlate with that of serum testosterone levels. Serious adverse effects were not
observed and no significant anticancer effects were observed with the intake of these two
mushrooms in the study population.
Sodium pyroglutamate isolated from Agaricus blazei has been shown to have potent antitumour and anti-metastatic actions, as well as immune-modulatory activity, in tumourbearing mice (Kimura et al., 2004).
Oral administration of ergosterol, isolated from the lipid fraction of Agaricus blazei Murill
has also been shown to have anti-tumour activity in Sarcoma 180-bearing mice.
Ergosterol reduced tumour growth at doses of 400 and 800mg/kg. Administration of
ergosterol for 20 days was reported to be without side effects, such as decreases in body,
epididymal adipose tissue, thymus, and spleen weights and leukocyte numbers induced
by cancer chemotherapy drugs. Ergosterol had no cytotoxicity against tumour cells and it
appears as though the antitumour activity of ergosterol might be due to direct inhibition of
angiogenesis induced by solid tumours (Takaku et al., 2001).
The effects of low molecular weight products extracted from Agaricus blazei Murill on
MethA tumour cell growth have been studied. Inoculation of a low molecule fraction (LM)
into the primary tumour of a two-tumour mouse model resulted in a marked inhibition of
the tumour, not only in the right flank, but also in the non-injected left flank.
Chromatographic purification and physicochemical characterization showed the main
tumouricidal activity to be located in a low molecule fraction-3 (LM-3), containing alpha1,4-glucan-beta-1,6-glucan complex with an average molecular weight of 20kDa. Serum
164
levels of immunosuppressive acidic protein (IAP) in mice receiving LM fractions,

particularly LM-3, significantly increased, indicating the possible activation of granulocytes
(Fujimiya et al., 1999).
Induction of apoptosis in human gastric epithelial AGS cancer cells by an aqueous extract
of Agaricus blazei has been demonstrated. It was found that an Agaricus blazei extract
could inhibit cell growth in a dose-dependent manner, which was associated with the
arrest of G2/M phase and the induction of apoptotic cell death via caspase-3 activation
(Jin et al., 2006). A subsequent study by the same group has shown a similar effect on
apoptosis by Agaricus blazei on human leukemic U937 cells via similar mechanisms
(regulation of Bcl-2 and caspase-3) (Jin et al., 2007).
The effect of an RNA-protein complex isolated from A. blazei Murill, on human leukemia
HL-60 cells has been studied. Typical apoptotic characteristics were determined by
morphological methods using DNA agarose gel electrophoresis and flow cytometry. The
data showed that the fraction from Agaricus blazei induced HL-60 cell apoptosis and that
the combined effect of down-regulation of telomerase activity and up-regulation of mRNA
expression of the caspase-3 gene could be the primary mechanism of induction of
apoptosis. These findings provide good evidence that the isolated fraction may be of value
for the clinical treatment of acute leukemia (Gao et al., 2007). Inhibitory effects of Agaricus
blazei extracts on human myeloid leukemia cells NB-4 and K-562 cells have also been
reported (Kim et al., 2009a).
An extract from fruit bodies of Agaricus blazei has been evaluated in a "double grafted
tumour system" mouse model and reported to cure the primary tumour and inhibit the
growth of metastatic tumours in this model. A separate extract from Agaricus blazei
(Himematsutake) inhibited the growth of the primary tumour. An immuno-suppresive
acidic protein (IAP) was induced by both the Agaricus and Himematsutake preparations
but not by Lentinus edodes. Lentinus edodes had no effect on the growth of either the
primary or metastatic tumours (Ebina, 2005).
An aqueous extract of Agaricus blazei has been shown to exert a hepato-protective effect
on both liver toxicity and hepato-carcinogenesis on rat liver toxicity induced by different
doses of diethylnitrosamine (Barbisan et al., 2002).
A subsequent study from another group has also demonstrated the chemo-preventative
potential of an Agaricus blazei (Ab) Murrill mushroom meal in a medium-term rat liver
165
carcinogenesis assay. Male Wistar rats initiated for hepatocarcinogenesis with

diethylnitrosamine (DEN, 200mg/kg i.p.) were fed during a 6-week period with dry
powdered mushroom strains Ab 29 or 26, each one with opened (OB) or closed
basidiocarp (CB), mixed at a level of 10% in a basal diet. Chemo-preventative activity of
the mushroom meal was observed for the Ab 29 (OB and CB) and Ab 26 (CB) strains in
terms of the number of putative pre-neoplastic altered foci of hepatocytes which express
either the enzyme glutathione S-transferase, placental form (GST-P+) or the transforming
growth factor-alpha, and for the Ab 29 (OB) and Ab 26 (CB) strains on the size of GST-P+
foci. This was associated with inhibition of foci cell proliferation in the animals fed the Ab
29 (OB) and Ab 26 (CB) strains. The results suggest that the protective influence of the
Ab meal against the DEN potential for rat liver carcinogenicity depends on both the strain
and period of mushroom harvest (Pinheiro et al., 2003).
The effects of crude extracts of the mushroom Agaricus blazei Murrill (Agaricaceae) on
both DNA damage and placental form glutathione S-transferase (GST-P)-positive liver foci
induced by diethylnitrosamine (DEN) have also been investigated in adult male Wistar
rats. The data indicated that previous treatment with the highest concentration of Agaricus
blazei (11.5mg/ml) significantly reduced DNA damage, indicating a protective effect
against DEN-induced liver cytotoxicity/genotoxicity (Barbisan et al. 2003a) while in a
subsequent study, the same group reported that treatment with aqueous extracts of
Agaricus blazei does not exert a protective effect against the development of GST-Ppositive foci induced by DEN (Barbisan et al., 2003b).
Anti-bacterial effects of Agaricus blazei Murill (AbM) have been investigated. The AbM
extract protected against systemic Streptococcus pneumoniae 6B infection in mice and
was most effective when given 24h before inoculation but it also had protective effects
when given together with challenge compared with control. The lack of an antibiotic effect
on pneumococci in vitro and increased levels of cytokines MIP-2 and TNF in the serum of
mice receiving AbM extract, indicated that the protective effect of AbM was due to the
involvement of the native immune system. The anti-infection properties of AbM have
therefore been shown in vivo and the results suggest that AbM extract may be useful as
an additional prophylactic and possibly therapeutic treatment against bacterial infections
in humans (Bernardshaw et al., 2005a).
A subsequent study by the same group has shown that an extract of Agaricus blazei Murill
can protect against lethal septicemia in a mouse model of faecal peritonitis. Bacterial
septicemia can occur during gastroenterological surgery. The putatively anti-infective
166
immunomodulatory action of Agaricus blazei Murill (AbM) has been studied in an

experimental peritonitis model in BALB/c mice. The mice were orally given an extract of
AbM or phosphate-buffered saline 1 day before the induction of peritonitis with various
concentrations of faeces from the mice. The state of septicemia, as measured by the
number of colony-forming units of bacteria in blood, and the survival rate of the animals
were compared between the groups. Mice that were orally treated with Agaricus blazei
Murill extract before bacterial challenge showed significantly lower levels of septicemia
and improved survival rates (Bernardshaw et al., 2006).
A recent study has demonstrated that ultrafiltration, in combination with spray-drying, is
applicable for the preparation of protein-bound polysaccharide powders with higher antitumour activities from Agaricus Blazei Murill (Hong et al., 2007). Thermostable antioxidant
activity has also been reported from Agaricus blazei Murill (Izawa and Inoue, 2004).
A study to evaluate the chronic toxicity and oncogenicity of Agaricus blazei Murill in F344
rats has recently been reported (Lee et al., 2008). Long-term (2 years) feeding of rats of a
powdered diet containing Agaricus blazei at levels up to 25,000 ppm (parts per million)
revealed no remarkable change in mean body weight, body weight gain, hematologic or
serum chemistry parameters, or absolute or relative organ weights in control or treatment
groups. Mortality in male treatment (mushroom) groups was significantly lower than in
controls. Histopathological studies showed no increased incidence of tumours.
A study has also reported good bioavailablity of both copper and zinc from mycelium of
Agaricus blazei Murrill equating to very good levels of recommended daily intakes of these
minerals from small amounts of (1g) of this mushroom (Rabinovich et al., 2007).
Anti-viral activities of Agaricus blazei Murill have been demonstrated against cytopathic
effects induced by western equine encephalitis (WEE) virus by the mycelial fractions but
not those of fruiting bodies (Sorimachi et al., 2001).
Ethanol extracts and hot water extracts of Agaricus blazei, Agrocybe cylindracea, and
Boletus edulis have been shown to have significant antioxidant properties. The ethanolic
extracts were more effective than hot water extracts in antioxidant activity using the
conjugated diene method and scavenging ability on 1,1-diphenyl-2-picrylhydrazyl radicals
whereas hot water extracts were more effective in reducing power, scavenging ability on
hydroxyl radials and chelating ability on ferrous ions as demonstrated by their lower EC50
values. Naturally occurring antioxidant components including total tocopherols (3.18-
167
6.18mg/g) and total phenols (5.67-5.81mg/g) were found in the extracts and their contents
were associated with the EC50 value of the antioxidant properties (Tsai et al., 2007).
Differences of the pharmacological effects of Agaricus blazei cultured on various materials
have been examined. Agaricus blazei mushrooms were prepared on culture media
composed of 1) tops of sugar cane shoots (stems and leaves), 2) rice straw 3) wheat
straw, 4) broad leaf tree bark, and 5) used substrate after Pleurotus ostreatus cultivation.
The pharmacological effects of this mushroom were examined by the following methods;
1) anti platelet aggregation stimulated by PAF or arachidonic acid Na, 2) inhibition of IL-8
gene expression stimulated by TNF-alpha, 3) improvements of rough surfaces by using
replica method. In both the anti-platelet aggregation test and chemokine gene revelation
control test, A. blazei cultured on the top shoot of sugar cane medium showed the most
effective results compared with that cultured on other media. The results suggested that
the A. blazei cultured on the top shoot of sugar cane medium has increased
pharmacological activity compared to mushrooms cultured on rice or wheat straw or broad
leaf bark (Yoshimoto et al., 2005).
An aqueous extract of Agaricus blazei Muril administered daily starting 40 days after the
onset of streptozotocin-induced diabetes in Wistar rats assisted in the recovery of
pulmonary tissue of the rats. Pulmonary lipoperoxidation increased in the diabetic animals
compared to the control group, followed by a reduction in the A. Blazei-treated group.
iNOS was increased in the lung in diabetic rats and reduced in the A. Blazei-treated
group. The pulmonary tissue in diabetic rats showed oxidative alterations related to the
streptozotocin treatment. The A. Blazei treatment effectively reduced the oxidative stress
and contributed to tissue recovery (Di Naso et al., 2010).
Using apolipoprotein E-deficient (ApoE(-/-)) mice, an experimental model of
atherosclerosis, the effects of supplementation of mice with Agaricus blazei for 6 or 12
weeks has been studied on the activation of immune cells in the spleen and blood and on
the development of atherosclerosis. Food intake, weight gain, blood lipid profile, and
glycemia were similar between the control and supplemented groups. To evaluate
leukocyte homing and activation, mice were injected with radiolabeled leukocytes, which
showed enhanced leukocyte migration to the spleen and heart of A. blazei-supplemented
animals. Analysis of the spleen showed higher levels of activation of neutrophils, NKT
cells, and monocytes as well as increased production of TNF-alpha and IFN-gamma.
Circulating NKT cells and monocytes were also more activated in the supplemented
group. Atherosclerotic lesion areas were larger in the aorta of supplemented mice and
168
exhibited increased numbers of macrophages and neutrophils and a thinner fibrous cap.
A. blazei-induced transcriptional upregulation of molecules linked to macrophage
activation (CD36, TLR4), neutrophil chemotaxy (CXCL1), leukocyte adhesion (VCAM-1),
and plaque vulnerability (MMP9) were seen after 12 weeks of supplementation. The data
show that the immunostimulatory effect of A. blazei has proatherogenic repercussions. A.
blazei enhanced local and systemic inflammation, upregulating pro-inflammatory
molecules, and enhancing leukocyte homing to atherosclerosis sites without affecting the
lipoprotein profile (Goncalves et al., 2011).
Reactive oxygen free radicals have been reported to be important in ischemia-reperfusion
injury cascades. Agaricus Blazei Murill (ABM) extract, previously reported to modulate
oxidative stress, increased the survival of rat cardiomyocytes (H9c2 cell line) without
cytotoxicity. Pretreatment with ABM extract reduced hydrogen peroxide-induced cell
damage and increased cell survival. ABM-pretreated rats that underwent myocardial
ischemia-reperfusion had greatly reduced infarct areas compared to those in the control
group. ABM may have a cardioprotective effect by increasing antioxidant activity, which
greatly ameliorates myocardial injuries caused by myocardial ischemia-reperfusion
injuries (Huang et al., 2010a).
The effects of an extract of Agaricus blazei Murrill (ABM) has been evaluated on HT-29
human colon cancer cells in severe combined immunodeficiency (SCID) mice. Oral
administration of ABM (up to 45 mg ABM daily for 6 weeks) did not prevent tumor growth,
but compared with the control group (0 mg ABM), the tumor mass appeared to grow more
slowly following ABM doses of 4.5 and 45 mg) (Wu et al., 2011b).
Supplementation with Agaricus blazei, carried out under pre-treatment, simultaneous
treatment, post-treatment and pre-treatment+continuous conditions, has shown that A.
blazei did not have genotoxic activity but showed antigenotoxic activity (Comet assay).
Supplementation caused an increase in the number of monocytes and in phagocytic
activity, suggesting that supplementation increases a proliferation of monocytes,
consequently increasing phagocytic capacity especially in the groups pre-treatment,
simultaneous and pre-treatment+continuous. The data suggest that A. blazei could
promote immunomodulation which can account for the destruction of cells with DNA
alterations that correlate with the development of cancer, since this mushroom was
demonstrated to have a preventive effect against pre-neoplastic colorectal lesions
evaluated by the aberrant crypt foci assay (Ishii et al., 2011).
169
Mechanistic studies of apoptosis in human hepatocellular carcinoma cells have shown

that Agaricus blazei Murill is able to act as an enhancer to sensitize doxorubicin (Dox)mediated apoptotic signaling, and this sensitization can be achieved by enhancing
intracellular Dox accumulation via the inhibition of NFkappaB activity. These findings
suggest that Agaricus blazei Murill, when combined with low doses of Dox, may have the
potential to provide more efficient therapeutic effects against drug-resistant human
hepatocellular carcinoma (Lee and Hong, 2011).
The immunomodulatory effects of Agaricus blazei Murill and resultant impacts on an array
of health outcomes have recently been reviewed (Hetland et al., 2011, Lima et al., 2011).
Agaricus brasiliensis
Ethanol extracts (0.9 mg/ml) and hot water extracts (0.7
mg/ml) of Agaricus brasiliensis Mural (ABM) caused
morphological changes and significantly reduced viability of
human oral cancer CAL 27 Cells after 48 h of treatment.
Both extracts were able to induce apoptotic cell death in
CAL 27 cells via the release of cytochrome c from
mitochondria into the cytoplasm and activation of caspase-3
in vitro (Fan et al., 2011).
Agaricus brasiliensis (previously named Agaricus blazei ss.
Heinem), also known as the sun mushroom, is native to Southeastern Brazil, and is widely
consumed, mainly in the form of tea. Aqueous (AqE) and ethanol (EtOHE) extracts and an
isolated polysaccharide (PLS) from the fruiting body of A. brasiliensis have been
evaluated for anti-viral activity against poliovirus type 1 in HEp-2 cells. The evaluation of
the time of addition by plaque assay showed that when AqE, PLS and EtOHE were
added, just after the virus inoculation (time 0 h), there was a concentration-dependent
reduction in the number of plaques by up to 50%, 67% and 88%, respectively. The test
substances showed anti-viral activity and were more effective when added during the
poliovirus infection. As the extracts had little effect on reducing viral adsorption and did not
show any virucidal effect, the authors suggested that they may act at the initial stage of
the replication of poliovirus (Faccin et al., 2007).
170
Studies with an aqueous extract of Agaricus brasiliensis S. Wasser et al. (=Agaricus

blazei Murrill sensu Heinem.) failed to show any anti-microbial effects against Salmonella
enterica serovar Typhimurium (Fantuzzi et al., 2011) nor on immunomodulatory properties
(Fantuzzi et al., 2010).
The mycelium polysaccharide and exo-polysaccharide (EPS) of Agaricus brasiliensis LPB
03 produced by submerged fermentation has shown strong inhibition against Sarcoma
180 in mice, reaching 72.19% inhibition compared to a control group. Furthermore, 50% of
mice in the test group demonstrated total tumour regression (Fan et al., 2007).
The structure and anti-tumour activity of polysaccharide fractions of the fruit body of
Agaricus brasiliensis have been studied in cold and hot water extracts (CWE and HWE)
on a mouse diabetic model (C57BL Ksj-db/db). Compared to the water administered
control group, the body weight, urinary glucose exclusion, urinary pH, blood glucose level,
and organs weight were comparable. The splenocytes of CWE administered mice
produced a higher concentration of interleukin-6. By megascopic and microscopic
examinations of renal sections, the number of the mice having abnormal kidney was 3/5
(control), 2/5 (HWE), and 0/5 (CWE) suggested the activity of the renal protection in the
cold water extract. The results strongly suggest that the pharmacological action of the cold
water extract of A. brasiliensis is significantly stronger than that of the hot water extract
(Furukawa et al., 2006).
The administration of ethanol-soluble, boiling water-soluble, and ammonium oxalateinsoluble fractions isolated from the fruiting bodies of Agaricus brasiliensis into C3H/HeN
mice has been shown to play an important role in the maintenance of hematopoietic cells
for compromised patients at the risk of infection associated with malignancy (Fujimiya et
al., 2006).
Determination of the phenolic and organic acid contents of Agaricus brasiliensis as well as
the antioxidant activities of its fruiting bodies and its mycelia obtained from submerged
cultivation has shown the presence of 3 phenolic compounds (gallic acid, syringic acid
and pyrogallol) and 8 organic acids( benzoic, oxalic, malic, acetic, alpha-ketoglutaric,
citric, fumaric and trans-aconitic acids). All extracts possessed antioxidant properties. The
fruiting body extracts were more effective in the DPPH radical scavenging activity and lipid
peroxidation inhibition than the mycelia extracts. The mycelia extracts however were more
effective in the ABTS radical scavenging activity and ferrous ion chelating ability (Carvajal
et al., 2012). Phenolic compounds present in mushroom extracts from A. brasiliensis
171
strongly generated reactive oxygen species (suggesting immunomodulatory effects) in

human PBMCs and K 562 cells in vitro (Wei et al., 2008).
An Agaricus brasiliensis-derived cold water extract has also been reported to have some
water-soluble toll-like receptor ligand complexes and induce cytokine production via a tolllike receptor 2-dependent mechanism (Yamanaka et al., 2011).
Agaricus sylvaticus
A randomized, double-blind, placebo-controlled
clinical trial carried out in Brazil over a six month
period with 56 patients has studied life quality of
postsurgical patients with colorectal cancer after
supplementation of the diet with Agaricus
sylvaticus (30 mg/kg/day). After six months of
treatment, the supplemented group had increased
physical activity, improved disposition and mood, reduced complaints of pain and reduced
alterations of sleep such as insomnia and restless sleep. The supplemented group also
presented with increased appetite, reduced constipation, diarrhea, alternate
diarrhea/constipation, flatulence, flatus retention, pyrosis, postprandial fullness, nausea,
abdominal distention and abdominal pain, indicators which were not observed in the
placebo group (Fortes et al., 2010).
A further evaluation of the same patients reported that the Agaricus sylvaticus group had
significantly reduced fasting plasma glucose (p = 0.02), total cholesterol (p = 0.01),
creatinine (p = 0.05), aspartate aminotransferase (p = 0.05), alanine aminotransferase (p
= 0.04), IgA (p = 0.0001), IgM (p = 0.02), systolic blood pressure (p = 0.0001)and diastolic
blood pressure (p = 0.0001), all effects that were not observed in the placebo group. The
data suggest that dietary supplementation with Agaricus sylvaticus was capable of
providing metabolic benefits to the biochemical, enzymatic and blood pressure
parameters of these patients with colorectal cancer in the postsurgical phase (Fortes and
Novaes, 2011).
172
Agrocybe aegerite (Black Poplar, Piopinno, Chiodini)

Agrocybe aegerita is an edible mushroom
with reported anti-tumour properties. An
investigation of bioactivity gave positive
results for ceramide, methyl-beta-Dglucopyranoside and alpha-Dglucopyranoside, along with linoleic acid and
its methyl ester. Ceramide inhibited the
cyclooxygenase (COX) enzymes, COX-1 and
-2 and its anti-cancer potential was investigated against five human cancer cell lines in
vitro and it was found to inhibit the proliferation of stomach, breast and central nervous
system cancer cell lines suggesting that the compound may be useful in alleviating
inflammatory conditions, as well as possibly reducing the development of the above
cancers (Diyabalanage et al., 2008).
A lectin from Agrocybe aegerita (AAL) has been found to possess potent tumoursuppressing function and tumour cell apoptosis-inducing activity. Its full sequence has
been published. It has been reported that this lectin is a member of the galectin family and
the dimeric form is the active unit for functional performance. The recombinant lectin
showed comparable tumour cell apoptosis-inducing activity with the wild lectin but no
DNase activity (Yang et al., 2005, Yang et al., 2009).
Antioxidant activity of a methanol crude extract and its fractions, from the fruiting bodies of
Agrocybe aegerita, has been evaluated by scavenging activity of 2,2'-azinobis-(3ethylbenzthiazoline-6-sulphonic acid) radical cation (ABTS(+)) and inhibition of lipid
peroxidation of rat brain homogenate. The ethyl acetate (EA) fraction, which showed the
most potent antioxidant activity in the above two assays, was further fractionated by a
Sephadex LH-20 column into four subfractions (EA1-EA4). Significant correlation was
found between the total phenolic content and the antioxidant activity in the EA fraction and
its sub-fractions (Lo and Cheung, 2005).
Proliferation of human leukemic U937 cells has been shown to be significantly inhibited by
conditioned medium of human peripheral blood mononuclear cells stimulated with coldwater extracts (10-800 g/mL of medium) of dietary mushrooms, Hypsizigus mamoreus,
Agrocybe aegerita and Flammulina velutipes (Ou et al., 2005).
173
A lectin isolated from Agrocybe aegerita has been shown to bind to the surface of
hepatoma cells, leading to induced cell apoptosis in vitro, and to exert an anti-hepatoma
effect in vivo via inhibition of tumor growth and extending the survival time of tumor
bearing mice (Jiang et al., 2012).
Agrocybe chaxingu
A beta-glucan from Agrocybe chaxingu significantly
inhibited lipopolysaccaride (LPS)-induced nitric oxide
(NO) and cyclooxygenase-2 (COX-2) expression levels
in murine macrophage Raw 264.7 cells. Furthermore,
topical application of the polysaccharide resulted in
marked inhibition of 12-O-tetradecanoylphorbol 13acetate (TPA)-induced ear edema in mice. These results suggest that this polysaccharide
may be useful for the treatment of NO- and COX-2-related disorders such as inflammation
(Lee et al., 2009a).
Osteoclast forming suppressive compounds (important in osteoporosis) have been
isolated from the mushroom Agrocybe chaxingu (Abel et al., 2007).
Antrodia cinnamomea
A 90-day sub-chronic oral toxicological assessment of
Antrodia cinnamomea, a medicinal mushroom has been
recently completed in 80 Sprague-Dawley rats. Doses of
3000, 2200 and 1500 mg/kg BW/day were given for 90
consecutive days and reverse osmosis water was used
as control. All animals survived to the end of the study.
During the experiment period, no abnormal changes
were observed in clinical signs, body weight and ophthalmological examinations. No
significant differences were found in urinalysis, hematology and serum biochemistry
parameters between the treatment and control groups. Necropsy and histopathological
examination indicated no treatment-related changes. The no-observed-adverse-effect
level (NOAEL) of Antrodia cinnamomea was identified to be greater than 3000 mg/kg
BW/day (the highest dose tested in this study) in Sprague-Dawley rats (Chen Tai et al.,
174
2011a). A further toxicological study on this mushroom in pregnant Sprague Dawley rats
concluded that this mushroom has no teratogenic effects in female rats (Chen Tai et al.,
2011b).
Auricularia auricular (Wood Ear)

In vitro evaluation of antioxidant activities of Auricularia
auricular has shown significant inhibition of lipid peroxidation,
and potent hydroxyl radical scavenging activity when
compared with the drug catechin. The IC50 value of crude,
boiled and ethanolic extracts of A. auricula represented 403,
510, and 373mg/ml respectively of hydroxyl radical scavenging
activity and 310, 572 and 398mg/ml respectively of lipid
peroxidation, while crude, boiled and ethanolic extracts were
shown to significantly increase nitric oxide production (664,
191 and 850pmole/mg dry wt/h respectively) over the control (Acharya et al., 2004).
Auricularia auricula polysaccharides have also recently been reported to have a positive
effect on heart function of aged mice, possibly via their significant antioxidant activity (Wu
et al., 2010).
Auricularia auricular has been shown to have hypocholesterolemic properties (Cheung,
1996b).
Constipation is one of the most prevalent gastrointestinal complaints and high fiber intake
is recommended as an initial therapy for constipation. Ear mushrooms (Auricularia) are
known to have higher fiber contents (by ~50%) than other mushroom varieties. In patients
with functional constipation, fiber supplements using ear mushrooms has been shown to
significantly improve constipation related symptoms without serious side effects (Kim et
al., 2004b).
An acidic polysaccharide with anti-coagulant activity has been isolated from Auricularia
auricula using water, alkali or acid extracts. The alkali extract showed the highest anticoagulant activity and was further purified using gel filtration chromatography. The specific
anti-coagulant activity of the purified polysaccharide was 2 international units (IU)/mg and
its average mass was approximately 160kDa. The polysaccharide from this species of
mushroom contains mainly mannose, glucose, glucuronic acid and xylose but no sulfate
esters. Its anti-coagulant activity was due to catalysis of thrombin inhibition by anti-
175
thrombin, but not by heparin cofactor II. Inhibition of Factor Xa by anti-thrombin was not
catalyzed by the polysaccharide. The glucuronic acid residues were essential for the anticoagulant action of the mushroom polysaccharide since the activity disappeared after
reduction of its carboxyl groups. In ex vivo tests using rats orally fed with the
polysaccharide, an inhibitory effect on platelet aggregation was observed, as with aspirin,
a well-known anti-platelet agent. The authors suggested that polysaccharides from these
mushrooms may constitute a new source of compounds with action on coagulation,
platelet aggregation and, perhaps, on thrombosis (Yoon et al., 2003).
Auricularia polytricha (Jew's Ear)

The isolation of an anti-tumour polysaccharide from
Auricularia Polytricha and its effects on macrophage
activation has recently been reported (Yu et al., 2009b). The
isolated fraction of polysaccharides enhanced phagocytosis
of macrophages and stimulated nitric oxide (NO) release
and cytokine secretion of macrophage in a dose-dependent
manner. The fraction also augmented mRNA transcription of
inducible nitric oxide synthase (iNOS), tumour necrosis
factor (TNF)-alpha, interleukin (IL)-1 beta and IL-6 and increased the protein expression of
inducible nitric oxide synthase.
An immunomodulatory protein (APP) has been purified from the fruiting body of an edible
Jew's Ear mushroom, Auricularia polytricha, by extraction using 5% cold acetic acid in the
presence of 0.1% 2-mercaptoethanol, followed by ammonium sulfate fractionation, DE-52
and P,MonoQ anion-exchange chromatography. The molecular mass of APP was around
13.4kDa and its pI is approximately 5.1. APP is a simple protein without carbohydrate, and
can agglutinate mouse red blood cells. APP alone activates murine splenocytes, markedly
increasing their proliferation and gamma-interferon (IFN-gamma) secretion, and presented
no cytotoxicity in vitro. Although murine splenocytes are stimulated by the mitogen
concanavalin A (ConA), APP suppressed their proliferation in a dose-dependent manner.
APP also enhanced the production of both nitric oxide (NO) and tumour necrosis factoralpha (TNF-alpha) by LPS-induced RAW 264.7 macrophages. The data suggest that this
protein isolated from Auricularia polytricha is an immune stimulant (Sheu et al., 2004).
176
Coprinus comatus
Altered androgen receptor (AR) activity caused by point
mutations or signalling mechanisms that regulate AR
function has been proposed as a key mechanism in the
transition to the androgen-independent stage of prostate
cancer. It has been demonstrated that a hexane extract
prepared from Coprinus comatus ( C. comatus) strain
734 was able to reduce AR levels and prostate-specific
antigen gene expression in the LNCaP-treated cell line
(Dotan et al., 2011a). A further study from the same
group isolated 2 fractions from the same mushroom strain that inhibited AR-mediated
reporter activity and reduced the levels of AR and prostate-specific antigen (PSA)
transcripts in LNCaP cells. One of these fractions (F-32) also inhibited the proliferation
and clonigenicity of LNCaP cells and inhibited the binding of AR to the PSA enhancer
region and inhibited Akt-mediated AR phosphorylation at Ser 213 (Dotan et al., 2011b).
The pharmaceutical value of the Basidiomycota fungi Coprinus comatus has also been
reviewed by the same group (Dotan et al., 2010).
Cordyceps militaris
An extract of Cordyceps militaris has been shown
to suppress dextran sodium sulphate (DSS)induced acute colitis in mice and production of
inflammatory mediators from macrophages and
mast cells. The extract significantly attenuated
DSS-induced body weight loss, diarrhea, gross
bleedingand, prevented shortening of colon length
and crypt length, and suppressed epithelial damage, loss of goblet cells, loss of crypts,
and infiltration of inflammatory cells induced by DSS. In addition, the extract inhibited
iNOS and TNF-alpha mRNA expression in colon tissue of DSS-induced colitis and in
RAW264.7 cells. Cordyceps militaris extract suppressed degranulation of mast cells in the
colon of mice with DSS-induced colitis and in antigen-stimulated mast cells. The data
suggest that the extract from Cordyceps militaris has anti-inflammatory activity in DSSinduced acute colitis by down-regulating production and expression of inflammatory
mediators (Han et al., 2011).
177
Adenosine, iso-sinensetin and dimethylguanosine from fruiting bodies of Cordyceps

militaris have been shown to have antioxidant and HIV-1 protease inhibiting activities
(Jiang et al., 2011b).
Cordyceps sinensis (Caterpillar mushroom)

A Cordycep extract has recently been evaluated in asthmatic
children during remission stage (Sun et al., 2010). The Cordyceps
extract inhibited the proliferation and differentiation of Th2 cells and
reduced the expression of related cytokines by down-regulating the
expression of GATA-3 mRNA and up-regulating the expression of
Foxp3 mRNA in peripheral blood mononuclear cells. The extract was
able to alleviate the chronic allergic inflammation by increasing the
level of interleukin-10.
Vanadium-enriched Cordyceps sinensis (VECS), has been
hypothesized as a possible treatment approach to both diabetes and
depression, based on vanadium compounds having an ability to imitate the action of
insulin and C. sinensis having an antidepressant-like activity, and being able to attenuate
a diabetes-induced increase in blood glucose concentrations (Guo et al., 2010, Guo et al.,
2011). However, the hypothesis remains to be proven.
Cordymin, a peptide purified from Cordyceps sinensis has been reported to have a
neuroprotective effect in the ischemic brain, which is due to the inhibition of inflammation
and increase of antioxidants activity related to lesion pathogenesis (Wang et al., 2012b).
The synergistic effects of Cordyceps sinensis with the drug cyclosporine A in preventing
allograft rejection was recently reported in rats (Ding et al., 2009a) but a retrospectively
study by the same group has evaluated the immunoregulatory effect of a dry powder
preparation of Cordyceps sinensis mycelia on humans after renal transplantation (Ding et
al., 2009b). While there was no significant difference in graft survival rate or occurrence of
reject reaction, treatment did effectively protect liver and kidney, stimulate hemopoietic
function, improve hypoproteinemia, as well as reduce the incidence of infection and the
dosage of the drugs cyclosporine A and tacrolimus used, and therefore, it may be useful
for immunoregulation after organ transplantation.
178
An exo-polysaccharide fraction from cultivated Cordyceps sinensis has been shown to

have immunomodulatory and anti-tumour effects on (B16 melanoma) tumour-bearing
mice (Zhang et al., 2005). Cordyceps sinensis has also been shown to possess immunopotentiating effects in lupus-prone autoimmune (NZB/NZW) mice via action on peripheral
mononuclear T lymphocytes. These effects also reportedly attenuated the severity of
lupus in these mice (Chen et al., 2009). A polysaccharide isolated from cultured
Cordyceps sinensis (named cordysinocan), has also been reported to activate immune
responses in cultured T-lymphocytes and macrophages, partly via the induction of
cytokines (Cheung et al., 2009).
Cultivated mycelium of Cordyceps sinensis, sequentially extracted by petroleum ether
(PE), ethyl acetate (EtOAc), and ethanol (EtOH) showed a significant and dosedependent inhibitory effect on the proliferation of four cancer cell lines, MCF-7 breast
cancer, B16 mouse melanoma, HL-60 human pre-myelocytic leukemia and HepG2 human
hepatocellular carcinoma, with IC50 values below 132 mg/ml. A hot water extract failed to
show such activity. The EtOAc extract, in particular, had the most potent effect against all
four cancer cell lines, with IC50 values between 12mg/ml (on B16) and 45mg/ml (on MCF7). In contrast, it had much lower cytotoxicity against normal mouse bone marrow cells.
The EtOAc extract contained carbohydrates, adenosine, ergosterol and a trace amount of
cordycepin, of which ergosterol and related compounds were identified as a major class of
active constituents contributing to the in vitro cytotoxicity. In an animal test, the EtOAc
extract showed a significant inhibiting effect on B16-induced melanoma in C57BL/6 mice,
causing a 60% decrease of tumour size over 27 days (Wu et al., 2007b).
An extract of Cordyceps sinensis (CSE) has been tested in C57BL/6 mice implanted
subcutaneously with syngeneic EL-4 lymphoma cells. Oral administration of the extract
led to a reduction of tumour size and prolongation of the host survival time. As for the
activities of peritoneal macrophages, chemotaxis was dramatically depressed within a few
days after EL-4 transplantation up to the end of life, but treatment with CSE at -14, -7, -4,
+4, +7 and +10 days after the tumour transplantation augmented the activity about four
times greater than that of the control. Phagocytic activity of macrophages was also
decreased in tumour-bearing mice treated with cyclophosphamide (100mg/kg) 3 and 5
days after tumour transplantation, but administration of CSE restored the activity to more
than the normal level. The overall efficacy of CSE was tested with protective activity
against systemic infection by Salmonella enteritides. The tumour-bearing mice receiving
this extract lived significantly longer than the other groups without CSE (Yamaguchi et al.,
179
1990). Dried powder of cultured Cordyceps sinensis mycelium has also shown cytotoxic
effects towards promyelocytic leukemia HL-60 cells via a suggested dependency on sterol
constituents and the activation of caspases-3/7 (Matsuda et al., 2009).
A study has been conducted to investigate a hypocholesterolemic effect of a hot-water
fraction (HW) from cultured mycelia of Cordyceps sinensis. In mice fed a cholesterol-free
diet and those fed a cholesterol-enriched diet, body and liver weights were not
significantly different from those of the controls. The serum total cholesterol (TC) of all
mice groups administered HW (150 and 300mg/kg/d, respectively) with the cholesterolenriched diet decreased more than in the control group. Among the mice fed the
cholesterol-enriched diet, HW also increased the high-density lipoprotein (HDL)
cholesterol level, but decreased the very low-density lipoprotein plus low-density
lipoprotein (VLDL+LDL) cholesterol level. The changes in HDL-and VLDL+LDLcholesterol levels consequently decreased the atherogenic value. The results indicated
that HW in rats administered a cholesterol-enriched diet decreased the plasma cholesterol
level. The 300mg/kg dose had a significant effect on the serum total cholesterol level (Koh
et al., 2003).
Flammulina velutipes (Enoki)

Oral administration of 10mg/kg of an
immunomodulatory protein (termed FVE) purified
from Enoki mushroom (Flammulina velutipes) and
known as an activator for human T lymphocytes,
significantly increased the life span and inhibited
the tumor size of BNL 1MEA.7R.1 (BNL)
hepatoma-bearing mice. Oral administration of
FVE displayed anti-tumor activity through activating
both innate and adaptive immunity of the host to
prime a cytotoxic immune response and IFN-gamma played a key role in the anti-tumor
efficacy of FVE (Chang et al., 2010b).
Extracts prepared from the fruiting body of Flammulina velutipes with a high ergothioneine
content exhibited a stronger delay of the autoxidation activity of oxymyoglobin, whereas
extracts prepared from the spent culture medium of F. velutipes with higher phenolics
content showed more efficient antioxidant capacity against lipid oxidation. The amount of
180
ergothioneine was distributed highest in the inedible (base and mycelium) parts of the
mushroom. These results suggest that the inedible parts and spent culture medium of F.
velutipes could potentially be considered as a readily available source of natural
antioxidants (Bao et al., 2010).
It has been reported that there is currently no effective therapy for malignant estrogenindependent breast cancer. Screening of 38 species of edible mushrooms on human
estrogen-receptor positive (ER+) (MCF-7) and estrogen-receptor negative (ER-) (MDAMB-231, BT-20) breast cancer cells has been undertaken to select potential agents with
broad-spectrum anti-tumour activity against breast cancer cells. Water-based extracts of
three mushroom species, Coprinellus sp., Coprinus comatus and Flammulina velutipes
(CME, CCE and FVE, respectively), have been identified as anti-breast cancer agents.
The anti-tumour activities included marked growth inhibition of both ER+ and ER- breast
cancer cells, induction of rapid apoptosis on both ER+ and ER- cells, and significant
inhibition of MCF-7 tumour colony formation in vitro. The anti-proliferative and cytotoxic
activities of the three mushroom extracts were dose-dependent, regardless of the
hormone receptor status of the cancer cells. The degree of produced cytotoxicity on ERbreast cancer cells was very high. Mushroom extracts CME and FVE induced a rapid
(within 5 hours) apoptosis on MCF-7 and MDA-MB-231 cells. MCF-7 tumour colony
formation rate was reduced by 60% in CCE- and CME-treated cells and nearly completely
inhibited (99%) by FVE treatment. These results suggest that the mushroom species
Coprinus comatus, Coprinellus sp. and Flammulina velutipes contain potent anti-tumour
compounds for breast cancer. This finding is important due to the lack of
chemotherapeutic and chemo-preventive agents for ER- human breast cancer (Gu and
Leonard, 2006).
An anti-tumour polysaccharide, EA3 isolated from Flammulina velutipes (CURT. ex FR.)
SING. has been shown to be composed of D-glucose with the chemical structure of a
beta-(1 leads to 3)-glucan. Another anti-tumour polysaccharide (EA5) also isolated from F.
velutipes was fractionated and among the polysaccharides isolated, the highest molecular
weight polysaccharide (EA501) showed the highest anti-tumour activity. The component
sugars of EA501 were found to be D-glucose 42.3%, D-galactose 17.3%, D-mannose
12.2%, D-xylose 6.7% and L-arabinose 14.7% (Ikekawa et al., 1982).
A further study by the same group has shown that proflamin, isolated from the culture
mycelium of Flammulina velutipes (Curt. ex Fr.) Sing. is a weakly acidic glycoprotein
containing more than 90% protein and less than 10% carbohydrate, and has a molecular
181
weight of ~13,000Da. Proflamin has been shown to be markedly effective against the
syngeneic tumours, B-16 melanoma (B-16) and adenocarcinoma 755 (Ca-755) in the
mouse. The increases in median survival time of treated mice with B-16 and Ca-755 were
86% and 84%, respectively. Proflamin exhibited no cytocidal effect against the cultured
cell lines in vitro. Oral administration of proflamin produced no lethal or any other apparent
adverse effect in mice (Ikekawa et al., 1985). More recent studies by the same group have
shown that Oral administration of proflamin significantly intensified various
immunoresponses in tumour-bearing mice, but it was not very effective against the
immunity of healthy (non-tumour-bearing) mice (Maruyama and Ikekawa, 2007).
Oral administration of a protein from Flammulina velutipes has also been shown to
possess anti-tumor activity in mice through activation of both innate and adaptive
immunity of the host to prime a cytotoxic immune response with interferon-gamma having
an effect on the anti-tumor efficacy of the protein (Chang et al., 2010a).
Antioxidant activity of submerged cultured mycelium extracts of higher Basidiomycetes
mushrooms has recently been reported. Antioxidant properties were studied from 28
submerged cultivated mycelium Basidiomycetes strains of 25 species. Three solvents ethanol, water (culture liquid), and ethyl acetate were used for extraction. Water extracts
from Coprinus comatus, Agaricus nevoi, and Flammulina velutipes (Enoki) showed high
antioxidant activities (AA) at 2mg/ml. When the ethanol extracts were tested, the highest
AA were found in Agaricus nevoi, Omphalotus olearius, and Auricularia auricula-judae
extracts at a concentration of 2mg/ml. The AA of ethanol extracts from Agrocybe aegerita
and C. comatus increased from 46.6% to 82.7% and from 2.4% to 62.1%, respectively,
when the concentration of the extract increased from 2mg/ml to 4-8mg/ml with the authors
suggesting that the extracts could be suitable as antioxidative agents and bioproducts
(Asatiani et al., 2007a).
mushroom Enokitake (Flammulina velutipes) fiber. The results demonstrated that
mushroom fiber lowered the serum total cholesterol level by enhancement of the hepatic
low density lipoprotein (LDL) receptor mRNA (Fukushima et al., 2001).
Angiotensin-converting enzyme (ACE) inhibitory activity (which has an effect on blood
pressure reduction) has been demonstrated in the culture broth from Flammulina velutipes
(strain 414). Nutritional requirements for the production of ACE inhibitory activity from F.
velutipes were shown to include sucrose, ammonium acetate, and glutamic acid (Kim et
182
al., 2002).
Two cuparene-type sesquiterpenes, enokipodins C (1) and D (2), have been isolated from
culture medium of Flammulina velutipes (Enoki), along with enokipodins A (3) and B (4).
All the metabolites showed anti-microbial activity against the fungus Cladosporium
herbarum, and gram-positive bacteria, Bacillus subtilis and Staphylococcus aureus
(Ishikawa et al., 2001).
conditioned medium of human peripheral blood mononuclear cells stimulated with coldwater extracts (10-800mg/mL of medium) of dietary mushrooms, Hypsizigus mamoreus,
Agrocybe aegerite and Flammulina velutipes (Ou et al., 2005).
Antioxidative activities of Flammulina velutipes extract have also been reported to be able
to stabilize the fresh colour of tuna meat during ice storage (Bao et al., 2009).
Polysaccharides from Flammulina velutipes have been shown to promote the metabolic
activity of murine splenocytes and peritoneal exudate cells (PEC) and increase the
amounts of TNF-alpha, INF-gamma and IL-2 in the supernatants of splenocyte cultures,
and the amount of TNF-alpha in PEC cultures, with the most marked increase on TNFalpha level. Flammulina velutipes polysaccharides (100, 50, 25 mg/kg) raised the serum
levels of TNF-alpha and INF-gamma in Sarcoma-180 tumour-bearing mice. Flammulina
velutipes polysaccharides may regulate murine immune function through promoting the
production of TNF-alpha, INF-gamma and IL-2 (Chang et al., 2009a).
A single dose of gamma-aminobutyric acid (GABA) enriched Flammulina velutipes
(Enokitake) powder (0.9 mg GABA/kg) resulted in a significant lowering of systolic blood
pressure ( by 30 mmHg) in spontaneously hypertensive rats (SHR), but no effects were
observed in rats with normal blood pressure (Harada et al., 2011).
183
Ganorderma Lucidum (Reishi, Lingzhi)

The antioxidant properties of Ganoderma
lucidum (Lingzhi or Reishi) and its effects on
DNA damage and repair in lymphocytes have
been evaluated in a small cross-over human
intervention study with 7 healthy adults. Plasma
total antioxidant power and the effect on
lymphocyte DNA damage and repair were
assessed before and after each treatment of a
single dose (3.3 g) of G. lucidum or water (control). G. lucidum caused an acute increase
in plasma antioxidant power, but did not significantly affect the level or rate of repair in
lymphocytic DNA suggesting that the bioavailable antioxidants absorbed from G. lucidum
have no effect on DNA resistance to oxidative stress or repair in vivo (Wachtel-Galor et
al., 2010).
A 6 month open-label study in 51 patients with prostate cancer that ingested either
Senseiro, containing extracts from the Agaricus blazei Murill mushroom, or Rokkaku
Reishi, containing the Ganoderma lucidum mushroom has reported no serious adverse
effects, and no significant anticancer effects were observed with the intake of these two
mushroom supplements (Yoshimura et al., 2010) .
A series of trials evaluating Ganoderma lucidum in several disease states have been
carried out. The trials evaluated effects on cancer, Type II diabetes, coronary heart
disease, chronic hepatitis B, and neurasthenia. Treatment with Ganopoly for 12 weeks
showed hypoglycemic activity and produced some anti-viral and liver protective effects in
patients with chronic hepatitis B infection. However, the same treatment regimen did not
result in any objective response in late-stage cancer patients (Zhou et al., 2005). Overall,
the findings suggest that Ganopoly may have some pharmacological activities, although
clinical proof is lacking.
The efficacy and safety of Senseiro (containing extracts from Agaricus blazei Murill) and
Rokkaku Reishi, (containing the Ganoderma lucidum mushroom) have been evaluated
over 6 months in patients with prostate cancer in Japan (Yoshimura et al., 2010). Patients
with biochemical failure after radical treatment for non-metastasized prostate cancer were
enrolled in this open-label study. No partial response in terms of serum prostate-specific
184
antigen was observed. Alteration of serum prostate-specific antigen doubling time did not
correlate with that of serum testosterone levels. Serious adverse effects were not
observed and no significant anticancer effects were observed with the intake of these two
mushrooms in the study population.
A double-blind, placebo-controlled, randomized, and dose-ranging study has been carried
out in men with lower urinary tract symptoms (LUTS) to evaluate the safety and efficacy of
an extract of Ganoderma lucidum that shows the strongest 5-alpha-reductase inhibitory
activity among the extracts of 19 edible and medicinal mushrooms. In this trial, 88 men
over the age of 49 years who had slight-to-moderate LUTS were randomly assigned to 12
weeks of treatment with G. lucidum extract (6mg once per day) or placebo. The primary
outcome measures were changes in the International Prostate Symptom Score (IPSS)
and variables of uroflowmetry. Secondary outcome measures included changes in
prostate size, residual urinary volume after voiding, laboratory values, and the reported
adverse effects. G. lucidum was effective and significantly superior to placebo for
improving total IPSS with 2.1 points decreasing at the end of treatment. No changes were
observed with respect to quality of life scores, peak urinary flow, mean urinary flow,
residual urine, prostate volume, serum prostate-specific antigen, or testosterone levels.
Overall treatment was well tolerated with no severe adverse effects (Noguchi et al.,
2008a).
Ganoderma lucidum (Reishi, Lingzhi) has been reported to suppress the invasive
behaviour of breast cancer cells by inhibiting the transcription factor NF-kappaB and to
inhibit the growth of MDA-MB-231 breast cancer cells by modulating Akt/NF-kappaB
signaling (Jiang et al., 2004a).
A subsequent study by the same group on the proliferation of human estrogen-dependent
(MCF-7) and estrogen-independent (MDA-MB-231) breast cancer cells has reported that
G. lucidum inhibits proliferation of human breast cancer cells and contains biologically
active compounds with specificity against the estrogen receptor and NF-kappaB
(transcription factor) signalling (Jiang et al., 2006).
Aqueous extracts of fruiting bodies of Ganoderma lucidum, G. sinense, and G. tsugae
have been reported to have anti-tumour activities in human breast cancer cells and
immunomodulatory activities in murine lymphocytes. In addition, it has also been
suggested that the stipes of fruiting bodies of Ganoderma species should be included in
the preparation of extracts of these fungi in order to obtain the most comprehensive active
185
ingredients (Yue et al., 2006). An extract of Ganoderma lucidum has also been reported to
reduce chemically-induced mammary adenocarcinomas in Sprague Dawley rats (Lakshmi
et al., 2009).
The effect of G. lucidum on oxidative stress-induced metastatic behaviour of poorlyinvasive MCF-7 breast cancer cells has also been studied and it has been shown that G.
lucidum inhibited oxidative stress-induced migration of MCF-7 cells by the downregulation of mitogen activated protein kinase (MAPK) signalling, which is involved in
hormonal signalling cascades. G. lucidum suppressed oxidative stress stimulated
phosphorylation of extracellular signal-regulated protein kinases (Erk1/2), which resulted
in the down-regulation of expression of c-fos, and in the inhibition of transcription factors
AP-1 and NF-kappaB. The biological effect of G. lucidum on cell migration was mediated
by the suppression of secretion of interleukin-8 from MCF-7 cells exposed to oxidative
stress. These results suggest that G. lucidum inhibited the oxidative stress-induced
invasive behaviour of breast cancer cells by modulating Erk1/2 signaling and could
possibly be considered as an antioxidant in adjuvant cancer therapy (Thyagarajan et al.,
2006).
A further study by the same group has also shown that an extract from green tea (GTE)
increased the anti-cancer effect of G. lucidum extract (GLE) on cell proliferation
(anchorage-dependent growth) as well as colony formation (anchorage-independent
growth) of breast cancer cells. The effect was mediated by the down-regulation of
expression of the oncogene c-myc in MDA-MB-231 cells. Although individual GTE and
GLE independently inhibited adhesion, migration and invasion of MDA-MB-231 cells, their
combination demonstrated a synergistic effect, which was mediated by the suppression of
secretion of urokinase plasminogen activator (uPA) from breast cancer cells suggesting a
potential use of combined green tea and G. lucidum extracts for the suppression of growth
and invasiveness of metastatic breast cancers (Thyagarajan et al., 2007).
A protein from Ganoderma lucidum has also been shown to effectively promote the
activation and maturation of immature human monocyte-derived dendritic cells, preferring
a Th1 response, suggesting that the protein may possess a potential effect in regulating
immune responses (Lin et al., 2009b). These immunomodulatory effects were shown to
be mediated via NF-kappaB and Mitogen Activated Protein Kinase (MAPK) pathways.
186
Innate immune cells are activated by the binding of beta-glucan to the dectin-1 receptor.
Ganoderma lucidum binds to dectin-1 and has been shown to induce RAW264.7 mouse
macrophage cell secretion of several cytokines, including granulocyte colony-stimulating
factor, interleukin (IL)-6, regulated upon activation normal T cell expressed and secreted
(RANTES), tissue inhibitor of metalloproteinase-1, and tumor necrosis factor-alpha.
Ganoderma lucidum also induced both nitric oxide and inducible nitric oxide synthase
(iNOS). Treatment with an inhibitor of nuclear factor-kappa B (NF-kappa B) reduced the
induction of IL-1, IL-6, and iNOS in a concentration-dependent manner and expression of
toll-like receptor (TLR)2, TLR4, and TLR6 was increased by Ganoderma lucidum
treatment. The result indicates that Ganoderma lucidum induces macrophage secretion of
inflammatory cytokines, which was also potentiated by the presence of
lipopolysaccharide, likely by binding to dectin-1 and toll-like TLR-2/6 receptors, which
activate NF-kappa B and prompt the secretion of cytokines (Batbayar et al., 2011).
Polysaccharide fractions of Ganoderma lucidum have been shown to have potent
immunomodulating effects in pre-clinical trials. A clinical study of healthy volunteers
demonstrated that G. lucidum did not affect their immune functions. Subsequently, an
open-labeled study (i.e. not double blind or placebo controlled) aimed to evaluate the
effects of water-soluble G. lucidum polysaccharides (Ganopoly) in patients with advanced
colorectal cancer. Forty-seven patients were enrolled and treated with Ganopoly at 5.4
g/day for 12 weeks. In 41 assessable cancer patients, treatment with Ganopoly tended to
increase mitogenic reactivity to phytohemagglutinin (Gao et al., 2005). Larger double blind
trials are required to show if this is a real effect.
High immunomodulatory and protective effects against sarcoma 180 in mice fed with Ling
Zhi or Reishi mushroom Ganoderma lucidum (W. Curt.: Fr.) P. Karst.
(Aphyllophoromycetideae) mycelium has also been reported (Rubel et al., 2008).
Ganoderma lucidum (Leyss: Fr) Karst. has also been shown to trigger immunomodulatory
effects and reduce nitric oxide synthesis in Swiss male mice (Rubel et al., 2010). Phenolic
compounds present in mushroom extracts from G. lucidum have also been shown to
strongly generate reactive oxygen species (suggesting immunomodulatory effects) in
human PBMCs and K 562 cells in vitro (Wei et al., 2008). Gandoderma lucidum extracts
have also been shown to promote immune responses in normal BALB/c mice (Chang et
al., 2009a) and WEHI-3 leukemic BALB/c mice (Chang et al., 2009b).
It has been proposed that the immune-regulatory activity and selenium-containing
attribute of proteins from Ganoderma lucidum or selenium-enriched G. lucidum in the form
187
of selenocysteine and selenomethionine, may contribute to their antitumor activity (Du et

al., 2010).
The effects of Ganoderma lucidum (Basidiomycetes) polysaccharide (GL-PS) extract on
tumour volume and T(CD4+/CD8+) ratio of tumour infiltrating lymphocytes (TILs) in breast
cancer bearing mice have been studied. The results indicated that GL-PS (100mg/kg/day)
could effectively increase the delayed type hypersensitivity response against sRBC in
BALB/c mice. Furthermore, intraperitoneal injection of this extract in breast cancer bearing
mice could increase T-cell infiltration into the tumour. The authors concluded that GL-PS
can exhibit a potent immunomodulatory effect and may be used for potentiation of the
immune system against diseases such as cancer and other conditions in which the
immune response has been compromised (Mojadadi et al., 2006).
An alcohol extract from the spore of Ganoderma lucidum has also been shown to inhibit
the in vitro proliferation of human umbilical vein endothelial cells and MDA-MB-231 human
breast cancer cells. Further fractionation of the alcohol extract revealed that the ethyl
acetate fraction inhibited both cell lines in a dose-dependent manner from 2 to 40mg/ml
(Lu et al., 2004).
Ganoderic acid DM (GADM), a triterpenoid isolated from Ganoderma lucidum, inhibits cell
proliferation and colony formation in MCF-7 human breast cancer cells. The mechanisms
involved G1 cell cycle arrest, and apoptosis induced by GADM may be partially due to
GADM-induced DNA damage of the breat cancer cells (Wu et al., 2012).
Ganoderma lucidum has been shown to significantly decrease ovarian cancer cell
numbers in vitro in a dose-dependent manner. Ganoderma lucidum also inhibited colony
formation, cell migration and spheroid formation. Ganoderma lucidum also induced cell
cycle arrest at the G2/M phase, induced apoptosis by activating caspase 3, increased p53
but inhibited Akt expression (Zhao et al., 2011).
Lucidenic acids isolated from Ganoderma lucidum (YK-02) decreased cell population
growth of HL-60 leukemia cells. Treatment of HL-60 cells with lucidenic acid A, C, and N
caused cell cycle arrest in the G1 phase. Lucidenic acid B-induced apoptosis involved
release of mitochondria cytochrome c and subsequently induced the activation of
caspase-9 and caspase-3, which were followed by cleavage of poly(ADP-ribose)
polymerase (PARP). Pretreatment with a general caspase-9 inhibitor (Z-LEHD-FMK) and
caspase-3 inhibitor (Z-DEVD-FMK) prevented lucidenic acid B from inhibiting cell viability
188
in HL-60 cells (Hsu et al., 2008b). Further work by the same group has also shown that
Ganoderma lucidum polysaccharides induce macrophage-like differentiation in human
leukemia THP-1 cells via caspase and p53 a ctivation (Hsu et al., 2009). Ganoderma
lucidum has also been shown to induce apoptosis in NB4 human leukemia cells and to
affect the signal transduction kinases Akt and Erk (Calvino et al., 2010).
Ganoderma lucidum has also been shown to inhibit proliferation in a dose- and timedependent manner and induce apoptosis in human prostate cancer cells PC-3 (Jiang et
al., 2004b), and Ganoderma lucidum (Lingzhi) polysaccharides have been shown to have
an inhibitory effect on cervical cancer cells (CA Ski and HeLa cells) (Chen et al., 2010d).
The effects of Ganoderma lucidum on SW 480 human colorectal cancer cells have been
evaluated. A fraction containing mainly polysaccharides (GLE-1), and a triterpenoid
fraction without polysaccharides (GLE-2) were analyzed. The data showed that both GLE1 and GLE-2 significantly inhibited the proliferation of SW 480 cells. The inhibitory effect of
GLE-2 was much stronger than that of GLE-1. GLE-1 inhibited DNA synthesis in the cells
and reduced the formation of DPPH radicals indicating that G. lucidum extracts inhibit
proliferation of human colorectal cancer cells and possesses antioxidant activity (Xie et
al., 2006).
Aqueous extracts of the sporophores of eight mushroom species have been assessed for
their ability to prevent H2O2-induced oxidative damage to cellular DNA using the singlecell gel electrophoresis ("Comet") assay. The highest genoprotective effects were
obtained with cold (20C) and hot (100C) water extracts of Agaricus bisporus and
Ganoderma lucidum fruit bodies, respectively. These edible mushrooms therefore
represent a valuable source of biologically active compounds with potential for protecting
cellular DNA from oxidative damage (Rocha et al., 2002). Aqueous extracts of
Ganoderma lucidum (30.1%) have a relatively high Antioxidant Index (% relative to
quercetin) in vitro (Abdullah et al., 2012).
Protein extracts from selenium-enriched Ganoderma lucidum (Se-GLPr) have been
reported to possess strong DNA protective effects from oxidative damage, which
increased with the increase of Se content as suggested by chemiluminescence analysis,
indicating indirectly that Se plays an important role in increasing the antioxidant activities
of protein extracts. This was confirmed by spin-trapping experiments showing that SeGLPr exhibited higher activities of scavenging superoxide and hydroxyl radicals than its
analog, common Ganoderma lucidum extract. All Se-GLPr samples showed stronger
189
activities of attenuating the production of superoxide radical than that of hydroxyl radical
(Zhao et al., 2004). Polysaccharide extracts from Se-enriched G. lucidum have also been
shown to protect DNA from hydroxyl radical oxidative damage in a dose dependent
manner (Zhao et al., 2008).
A more recent study has examined the effects of an extract of Ganoderma lucidum for its
free-radical scavenging property and for effects on liver mitochondrial antioxidant activity
in aged BALB/c mice (50 and 250 mg/kg body weight for 15 days) (Cherian et al., 2009).
G. lucidum increased antioxidant status in liver mitochondria of aged mice compared with
the aged controls. The extract possessed significant 2,2-diphenyl-1-picrylhydrazil (DPPH),
2, 2'-azinobis (3-ethylbenzothiazolin-6-sulphonic acid) (ABTS) radical scavenging
activities and ferric reducing antioxidant power (FRAP) as well as superoxide and hydroxyl
radical scavenging activities.
A human toxicological study has evaluated the consumption of Lingzhi (Ganoderma
lucidum) in a double-blinded, placebo-controlled, cross-over intervention study on a range
of biomarkers for human health. The study investigated the effects of 4 weeks Lingzhi
supplementation (1.44g Lingzhi/d; equivalent to 13.2g fresh mushroom/d) on a range of
biomarkers for antioxidant status, cardiovascular disease (CHD) risk, DNA damage,
immune status, and inflammation, as well as markers of liver and renal toxicity. No
significant change in any of the biomarkers was found. The results showed no evidence of
liver, renal or DNA toxicity with Lingzhi intake (Wachtel-Galor et al., 2004).
The anti-invasive effect of lucidenic acids isolated from a Ganoderma lucidum strain (YK02) against human hepatoma carcinoma cells have been evaluated, with the results
indicating that the lucidenic acids isolated from G. lucidum (YK-02) were anti-invasive
bioactive components on human hepatoma carcinoma cells (Weng et al., 2007).
190
Triterpene-enriched extracts from Ganoderma lucidum have been shown to inhibit growth
of human hepatoma Huh-7 cells via suppression of protein kinase C, activating mitogenactivated protein kinases (intermediates in hormonal signalling pathways) and G2-phase
cell cycle arrest. In contrast, the extracts did not inhibit growth of Chang liver cells, a
normal human liver cell line (Lin et al., 2003).
Three triterpene aldehydes, lucialdehydes A - C, from the fruiting bodies of Ganoderma
lucidum, have been shown to have cytotoxicity against murine and human tumour cells
(Lewis lung carcinoma (LLC), T-47D, Sarcoma 180, and Meth-A tumour cell lines) (Gao et
al., 2002).
The induction of apoptosis by extracts of Ganoderma lucidum have previously been
reported, however, more recent data have proposed that the mechanisms involved (at
least in human gastric carcinoma cells) involve caspase pathways which are associated
with inactivation of the Akt signalling pathway (Jang et al., 2010b). Induction of apoptosis
and alterations in signal transduction kinases (Akt and Erk) by active fractions from
Ganoderma lucidum have also been reported in human leukemia cells (Calvino et al.,
2010).
Polysaccharides from the Lingzhi (Ganoderma Lucidum) have been shown to decrease
CyclinB1 mRNA expression in cervical cancer CaSki cells and inhibit CaSki and HeLa
cell proliferation (Chen et al., 2010d). Ganoderma lucidum has also been shown to inhibit
cell growth and disruption of cell cycle progression via down regulation of cyclin D1 in the
ovarian cancer cell line OVCAR-3. Chemopreventive activities were demonstrated by
suppression of oxidative stress via the induction of antioxidant SOD and catalase as well
as the phase II detoxification enzyme NAD(P)H:quinone oxidoreductase 1 (NQO1) and
glutathione S-transferase PI (GSTP1) via the Nrf2 mediated signaling pathway known to
provide chemoprotection against carcinogenicity (Hsieh and Wu, 2011).
The polysaccharide (PS) fractions from several medicinal herbs have been reported to
have anti-ulcer effects against experimental ulcers in the rat. The water-soluble PS
fractions from Ganoderma lucidum (Reishi mushroom) have been shown to inhibit
indomethacin-induced gastric mucosal lesions in rats. The effect of the PS fraction from
G. lucidum on the healing of gastric ulcers induced by acetic acid in the rat has
subsequently been studied. The results indicated that oral administration of G. lucidum PS
at 0.5 and 1.0g/kg for 2 weeks caused a significant acceleration of ulcer healing by 40.1%
and 55.9%, respectively. In mechanistic studies, additional rats were treated with 10M
191
acetic acid to induce acute ulcers, and then treated with G. lucidum PS (1.0g/kg) for 3, 7,
10, or 14 days. Treatment with G. lucidum PS at 1.0 g/kg significantly suppressed or
restored the decreased gastric mucus levels and increased gastric prostaglandin
concentrations compared with the control group. The results indicated that G. lucidum PS
is an active component with healing efficacy on acetic acid-induced ulcers in the rat, which
may represent a useful preparation for the prevention and treatment of peptic ulcers (Gao
et al., 2004).
Ganoderma lucidum, as well as Phellinus rimosus, Pleurotus florida and Pleurotus
pulmonaris, have been reported to have significant antioxidant activities (Ajith and
Janardhanan, 2007).
Cholesterol-lowering properties of Ganoderma lucidum have been demonstrated in vitro,
ex vivo, and in hamsters and mini-pigs. Organic fractions containing oxygenated
lanosterol derivatives inhibited cholesterol synthesis in T9A4 hepatocytes. In hamsters,
5% Ganoderma lucidum did not affect low density lipoprotein (LDL) but decreased total
cholesterol (TC) by 9.8%, and high density lipoprotein (HDL) by11.2%. Ganoderma
lucidum (2.5 and 5%) had effects on several faecal neutral sterols and bile acids. In minipigs, 2.5% Ganoderma lucidum decreased TC, LDL- and HDL cholesterol 20, 27, and
18%, respectively, increased faecal cholestanol and coprostanol; and decreased cholate
(Berger et al., 2004).
The hypolipidemic effect of the exo-biopolymer (EXBP) and endo-biopolymer (ENBP)
produced from a submerged mycelial culture of Ganoderma lucidum has been
investigated in dietary-induced hyperlipidemic rats. Hypolipidemic effects were achieved in
both the EXBP- and ENBP-treated groups, however, the former proved to be more potent
than the latter. The administration of the EXBP (100mg/kg body weight) substantially
reduced the plasma total cholesterol, low-density lipoprotein (LDL) cholesterol,
triglyceride, phospholipid levels, and atherogenic index by 31.0%, 39.0%, 35.4%, 28.1%,
and 53.5%, respectively, when compared to the control group. The EXBP also lowered
the liver total cholesterol, triglyceride, and phospholipid levels by 22.4%, 23.1%, and
12.9%, respectively. Furthermore, the high-density lipoprotein (HDL) cholesterol and ratio
of HDL cholesterol to total cholesterol were significantly increased (Yang et al., 2002b). A
hypolipidemic effect of Ganoderma lucidum (Leyss:Fr) Karst has also been demonstrated
in a mouse model (Rubel et al., 2011).
192
Possible immuno-modulating effects of Ganoderma lucidum mycelium extract (GL-M) and

spore extracts on human immune cells have been studied. Dendritic cells (DCs) are
antigen-presenting cells and their role in DC-based tumour vaccines has been well
defined. The differential effect of GL-M and GL spore extract (GL-S) on proliferation and
Th1/Th2 cytokine mRNA expression of human peripheral blood mononuclear cells
(PBMCs) and monocytes has been evaluated. The effects on the phenotypic and
functional maturation of human monocyte-derived DCs were also investigated. GL-M
induced the proliferation of PBMCs and monocytes, whereas GL-S showed a mild
suppressive effect. Both extracts stimulated Th1 and Th2 cytokine mRNA expression, but
GL-M was a relatively stronger Th1 stimulator. In contrast to GL-S, GL-M enhanced
maturation of DCs in terms of up-regulation of CD40, CD80, and CD86, and also reduced
fluorescein isothiocyanate-dextran endocytosis. Interestingly, GL-M-treated DCs only
modestly enhanced lymphocyte proliferation in allogenic mixed lymphocyte culture with
mild enhancement in Th development. The data provide evidence that GL-M has immunomodulating effects on human immune cells and may be of use as a natural adjuvant for
cancer immunotherapy with dendritic cells (Chan et al., 2005). Ganoderma lucidum has
also been shown to enhance the expression of CD40 and CD80 molecules on human
peripheral blood monocytic cells derived from both sexes in a dose-dependent manner
(Ahmadi and Riazipour, 2009).
A polysaccharide purified from Ganoderma lucidum has also been shown to induce gene
expression changes in human dendritic cells and promotes T helper 1 immune response
in BALB/c mice (Lin et al., 2006).
Ganoderma lucidum mycelia (0.2-1.6mg/ml) have also been reported to stimulate tumour
necrosis factor-alpha (TNF-alpha) and IL (interleukin)-6 production after 8h of treatment in
human whole blood. IFN (interferon)-gamma release from human whole blood was also
enhanced after 3 days of culture with Ganoderma lucidum mycelia (0.2-1.0mg/ml).
However, Ganoderma lucidum mycelia did not potentiate nitric oxide production in
RAW264.7 cells. An electrophoretic mobility shift assay revealed that the Ganoderma
lucidum mycelia (1.6mg/ml) activated kappaB DNA binding activity in RAW264.7 cells.
These results provide supporting evidence for the immunomodulatory effect of
Ganoderma lucidum mycelia (Kuo et al., 2006).
An extract from Ganoderma lucidum has been reported to have apoptotic and antiinflammatory functions in HT-29 human colonic carcinoma cells. Ling Zhi extract (LZE) is
a herbal mushroom preparation that has been shown to induce apoptosis anti-
193
inflammatory action and differential cytokine expression during induced inflammation in

the human colonic carcinoma cell line, HT-29. The extract caused no cytotoxicity in HT-29
cells at doses less than 10,000 mg/ml. Increasing concentrations reduced prostaglandin
E2 production, but increased nitric oxide production. LZE treatment induced apoptosis by
increasing the activity of caspase-3. RT-PCR showed that LZE at a concentration of
5,000mg/ml decreased the expression of cyclooxygenase-2 mRNA. Among 42 cytokines
tested by protein array in this study, supplementation of LZE at doses of 500 and
5,000mg/ml to HT-29 cells reduced the expression of interleukin-8, macrophage
inflammatory protein 1-delta, vascular epithelial growth factor, and platelet-derived growth
factor. These results suggest that LZE has pro-apoptotic and anti-inflammatory functions,
as well as inhibitory effects on cytokine expression during early inflammation in colonic
carcinoma cells (Hong et al., 2004).
Ganoderic acid T (GA-T) of Ganoderma lucidum inhibited proliferation of HCT-116 cells, a
human colon carcinoma cell line. Cell aggregation and adhesion assays showed that GAT promoted homotypic aggregation and simultaneously inhibited the adhesion of HCT-116
cells to the extracellular matrix (ECM) in a dose-dependent manner (Chen et al., 2010c).
Wound healing assays indicated that GA-T also inhibited the migration of HCT-116 cells in
a dose-dependent manner, and suppressed the migration of 95-D cells, a highly
metastatic human lung tumor cell line, in a dose- and time-dependent manner. In addition,
GA-T inhibited the nuclear translocation of nuclear factor-kappa B (NF-kappa B) and the
degradation of inhibitor of kappa B-alpha (I kappa B alpha), which leads to downregulated expression of matrix metalloproteinase-9 (MMP-9), inducible nitric oxide
synthase (iNOS), and urokinase-type plasminogen activator (uPA). Animal and Lewis
Ganodermanontriol, a lanostanoid triterpene from Ganoderma lucidum has been shown to
be able to modulate of the beta-catenin pathway, which is involved in the progression of
colorectal cancer. Ganoderma lucidum inhibited proliferation of HCT-116 and HT-29 colon
cancer cells without a significant effect on cell viability, while ganodermanontriol inhibited
transcriptional activity of beta-catenin and protein expression of its target gene cyclin D1
in a dose-dependent manner. A marked inhibitory effect was also seen on Cdk-4 and
PCNA expression, whereas expression of Cdk-2, p21 and cyclin E were not affected.
Ganodermanontriol also caused a dose-dependent increase in protein expression of Ecadherin and beta-catenin in HT-29 cells, and suppressed tumor growth in a xenograft
model of human colon adenocarcinoma cells HT-29 implanted in nude mice without any
side-effects and inhibited expression of cyclin D1 in tumors (Jedinak et al., 2011b). In HT29 human colon cancer cells, triterpenes from Ganoderma lucidum have also been shown
194
to induce programmed cell death (Type II-autophagy) via a mechanism involving inhibition
of p38 mitogen-activated kinase (p38 MAPK) (Thyagarajan et al., 2010).
The potential of an Ganoderma lucidum extract as a radioprotector and antioxidant
defense against oxygen radical-mediated damage has been studied and it was
demonstrated that a hot-water extract of Ganoderma lucidum had good radioprotective
ability, as well as protection against DNA damage induced by metal-catalyzed Fenton
reactions and UV irradiation, although the evidence was based on in vitro tests using
isolated DNA. It was also found that the water-soluble polysaccharide isolated from the
fruit body of Ganoderma lucidum was as effective as a hot-water extract in protecting
against hydroxyl radical-induced DNA strand breaks, indicating that the polysaccharide
compound is associated with the protective properties (Kim and Kim, 1999).
Oral administration of Ganoderma lucidum extract (GLE) to tumor-bearing Swiss albino
mice along with exposure to gamma radiation has been shown to result in tumour
regression. Single-cell gel electrophoresis (comet assay) on cells of normal and tumour
tissues from tumour-bearing animals treated with GLE and radiation, revealed that there
was significant reduction in radiation-induced damage to cellular DNA in normal tissues
compared to the tumour, indicating preferential protection to normal tissues and possible
use as an adjuvant in radiotherapy, for tumour regression and prevention of radiationinduced cellular damage in normal tissues (Gopakumar et al., 2010). Polysaccharides
isolated from Ganoderma lucidum have also been reported to enhance the repair of
radiation induced DNA strand breaks in human cells after 120min of exposure (Pillai et al.,
2010).
Reactive oxygen species have been reported to be involved in the pathogenesis of a
number of age-associated human health conditions. The mitochondrial respiratory chain is
a direct intracellular source of reactive oxygen species. Ganoderma lucidum (50 and 250
mg/kg) has been shown to enhance the activities of mitochondrial dehydrogenases and
complex I and II of the electron transport chain in the brain of aged male Wistar rats (Ajith
et al., 2009). The level of lipid peroxidation was significantly lowered in the Ganoderma
lucidum treated group compared to the aged controls. The activity exhibited by the extract
of Ganoderma lucidum was partially correlated to its antioxidant activity. If Ganoderma
lucidum is able to improve the function of mitochondria in the aged rat brain, then further
studies would be warranted to evaluate possible future applications against ageing
associated neurodegenerative diseases.
195
An aqueous extract of Ganoderma lucidum (0.03 and 0.3g/kg) has been shown to lower
the serum glucose level in obese/diabetic (+db/+db) mice after one week of treatment
whereas a reduction was observed in lean (+db/+m) mice only fed with 0.3g/kg of G.
lucidum at the fourth week. A higher hepatic PEPCK gene expression was found in
+db/+db mice. G. lucidum (0.03 and 0.3g/kg) markedly reduced PEPCK gene expression
in +db/+db mice whereas the expression of PEPCK was attenuated in +db/+m mice
(0.3g/kg G. lucidum). These data demonstrate that G. lucidum consumption can provide
beneficial effects in treating type 2 diabetes mellitus (T2DM) in mice by lowering the
serum glucose levels through the suppression of hepatic PEPCK gene expression (Seto
et al., 2009).
Ganoderma lucidum has been reported to possess both hypoglycaemic and antihyperglycaemic effects in Wistar rats (Mohammed et al., 2007), while Ganoderma lucidum
polysaccharides have also been shown to significantly and dose-dependently increase
nonenzymic and enzymic antioxidants, serum insulin level and reduce lipid peroxidation
and blood glucose levels in streptozotocin-induced diabetic rats (Jia et al., 2009).
Ethanol extracts of Ganoderma lucidum have been evaluated against the ovariectomized
(Ovx)-induced deterioration of bone density in 11-week-old female Sprague Dawley (SD)
rats (Miyamoto et al., 2009). The results showed that the G. lucidum-treated Ovx rats
showed improved bone density compared with the Ovx rats.
The induction of granulocyte macrophage colony-stimulating factor (GM-CSF) production
by water-soluble, polysaccharide components of Ganoderma lucidum (Reishi) mycelia,
possibly providing an anti-inflammatory effect in a mouse model of colitis has been
reported (Hanaoka et al., 2011).
Enhaced proliferation of bone marrow macrophages in a dose-dependent manner by
Lingzhi or Reishi medicinal mushroom Ganoderma lucidum immunomodulating substance
(GLIS) has been demonstated. Exposure of bone marrow macrophages to GLIS resulted
in significant increases in NO production, induction of cellular respiratory burst activity,
and increased levels of IL-1 beta, IL-6, IL-12p35, IL-12p40, IL-18, and TNF-alpha gene
expression and levels of TNF-alpha, IL-1 beta, and IL-12 secretion, indicating that GLIS
activates the immune system by modulating cytokine production (Ji et al., 2011, Zhe et al.,
2011).
196
Crude dichloromethane, ethanol, water, and polysaccharide extracts of Ganoderma

lucidum all suppressed HPV 16 E6, with the dichloromethane extract being the most
active. The extract of G. lucidum contained flavonoids, terpenoids, phenolics, and
alkaloids, although it is unknown which compounds in the extract were responsible for the
anti-viral effects (Lai et al., 2010).
Ganoderma lucidum (Reishi) selectively inhibits cancer cell viability in inflammatory breast
cancer although it does not affect the viability of noncancerous mammary epithelial cells.
Reishi has been shown to inhibit cell invasion and disrupt the cell spheroids that are
characteristic of inflammatory breast cancer. Reishi decreased the expression of genes
involved in cancer cell survival, proliferation, invasion and metastasis, whereas it
increases the expression of IL8 (Martinez-Montemayor et al., 2011).
Recombinant Ling Zhi-8 (rLZ-8), an immunomodulatory protein cloned from Ganoderma
lucidum (Reishi or Ling Zhi) inhibits the proliferation of A549 human lung cancer cells. The
antitumor effect was via a modulation of p53 via ribosomal stress. rLZ-8 inhibited lung
cancer cell growth in vitro and also in vivo, in mice transplanted with Lewis lung carcinoma
cells (Wu et al., 2011a). Recombinant Lz-8 (rLz-8) also induced endoplasmic reticulum
stress-mediated autophagic cell death in the human gastric cancer cell line SGC-7901,
but caspase inhibitors did not prevent rLz-8-induced cell death, and therefore the
autophagic response induced by rLz-8 is independent of caspase activation (Liang et al.,
2012). Lung Carcinoma (LLC) model experiments have demonstrated that GA-T
suppressed tumor growth and LLC metastasis and down-regulates MMP-2 and MMP-9
mRNA expression in vivo. These results indicate that GA-T effectively inhibits cancer cell
invasion in vitro and metastasis in vivo (Chen et al., 2010c).
The mycelial culture of Ganoderma lucidum has been shown to be highly active against
human pathogenic bacteria Escherichia coli, Staphylococcus aureus, Klebsiella
pneumoniae and Pseudomonas aeruginosa, with E.coli having the highest susceptibility to
the mushroom mycelia (Ofodile et al., 2011).
An ethanol extract of Ganoderma lucidum (Fr.) P. Karst, at oral doses of 500 mg/kg and
1000 mg/kg has been shown to attenuate Indomethacin-induced gastric ulceration in rats
(Rony et al., 2011).
The evidence for the anti-cancer effects of Ganoderma lucidum has been reviewed (Yuen
and Gohel, 2005), while the active compounds in G. lucidum and their effects have also
197
been reviewed (Boh et al., 2007). More recently, the pharmacological aspects, cultivation
methods and bioactive metabolites from Ganoderma lucidum and their potential role in
various therapeutic applications have been reviewed (Sanodiya et al., 2009). A further
review on the potential therapeutic properties of Ganoderma lucidum has also recently
been published (Deepalakshmi and Mirunalini, 2011). Furthermore, the in vitro and in vivo
effects of G. lucidum on cancer invasion and metastasis have been reviewed, with the
authors concluding that these effects occur through modulation of the phosphorylation of
extracellular signal-regulated kinase (ERK1/2), phosphatidylinositol 3-kinase (PI 3-kinase)
or Akt kinase (protein kinase B) (Weng and Yen, 2010).
Grifola Frondosa (Maitake)
An open trial with 80 patients with polycystic

ovary syndrome at three clinics in Japan has
been undertaken. Seventy-two patients were
randomly assigned to receive Maitake extract
(SX-fraction: MSX) or clomiphene citrate (CC)
monotherapy for up to 12 weeks. Eighteen (18)
patients who did not respond to MSX or CC were
subjected to combination therapy of MSX and CC
for up to 16 weeks. Eight (8) patients with documented history of failure to CC received
combination therapy from the beginning. Twenty-six (26) patients in the MSX group and
31 in the CC group were evaluated for ovulation. The ovulation rates for MSX and CC
were: 76.9% (20/26) and 93.5% (29/31), respectively by the patients (NS), and 41.7%
(30/72) and 69.9% (58/83), respectively, by the cycles ( p=0.0006). In the combination
therapy, 7 of 7 patients who failed in MSX monotherapy and 6 of 8 patients who failed in
CC monotherapy showed ovulation. The data suggest that the Maitake extract described
in this study may induce ovulation in patients with polycystic ovary syndrome and may be
useful as an adjunct therapy for patients who failed first-line treatment with clomiphene
citrate (Chen et al., 2010b).
A Systematic Review (the gold standard of reviews) has evaluated the scientific evidence
on Grifola frondosa (Maitake), including expert opinion, folkloric precedent, history,
pharmacology, kinetics/dynamics, interactions, adverse effects, toxicology, and dosing
198
(Ulbricht et al., 2009). The literature collected pertained to efficacy in humans, dosing,
precautions, adverse effects, use in pregnancy and lactation, interactions, alteration of
laboratory assays, and mechanisms of action. While animal studies report hypoglycaemic
effects and anti-cancer and immunostimulatory effects, the authors concluded that there
was a lack of systematic study on the safety and effectiveness of Maitake in humans and
future randomized controlled trials are required before efficacy in humans can be
substantiated.
A fraction extracted from Grifola frondosa (Maitake, GF-D) and its combination with
human interferon alpha-2b (IFN) has been investigated for an inhibitory effect on hepatitis
B virus (HBV) in HepG2 2.2.15 cells (2.2.15 cells). HBV DNA and viral antigens were
analyzed by a quantitative real-time polymerase chain reaction and end-point titration in
radioimmunoassays, respectively. The results showed that GF-D or IFN alone could
inhibit HBV DNA in the cells with the 50% inhibitory concentration (IC50) of 0.59mg/ml and
1399 IU/ml, respectively. The combination of GF-D and IFN for anti-HBV activity was also
evaluated and it was found that they synergistically inhibited HBV replication in 2.2.15
cells. In combination with 0.45mg/ml GF-D, the apparent IC50 value for IFN was 154 IU/ml.
This 9-fold increase in anti-viral activity of IFN suggested that GF-D could synergize with
IFN. The results indicate that the Grifola frondosa extract, in combination with human
interferon alpha-2b, might provide a potentially effective therapy against chronic hepatitis
B virus infections (Gu et al., 2006).
A further study by the same group has recently reported the purification of an anti-viral
protein from an extract of Grifola frondosa (Maitake) fruiting bodies. The protein inhibited
herpes simplex virus type 1 (HSV-1) replication in vitro with an IC50 value of 4.1g/ml and
a therapeutic index >29.3. Higher concentrations (125 and 500 g/ml) also significantly
reduced the severity of HSV-1 induced blepharitis, neovascularization, and stromal
keratitis in a murine model. Topical administration of the protein to the mouse cornea
resulted in a significant decrease in virus production. It was reported that the protein
directly inactivated HSV-1 while simultaneously inhibiting HSV-1 penetration into Vero
cells. The N (amino)-terminal sequence of the protein consisted of an 11 amino acid
peptide, NH2-REQDNAPCGLN-COOH that did not match any known amino acid
sequences, indicating that the protein is likely to be a novel anti-viral protein (Gu et al.,
2007).
Maitake D-fraction is a polysaccharide extracted from the Maitake mushroom (Grifola
frondosa S.F. Gray). Using normal C3H/Hej mice, its effects on the natural immune
199
system, including macrophages, dendritic cells, and natural killer (NK) cells, have been
investigated. NK cells attack cells infected with pathogens such as bacteria and viruses
and produce cytokines, such as interferon-gamma (IFN-), that can modulate natural and
specific immune responses. D-Fraction was administered to the mice intraperitoneally for
3 consecutive days. Spleen cells containing macrophages and dendritic cells were then
cultured and the culture supernatants were analyzed for IL-12. The results indicated that
the D-fraction stimulated the natural immunity related to the activation of NK cells
indirectly through IL-12 produced by macrophages and dendritic cells, and hence
administration of D-fraction to healthy individuals may serve to prevent infection (Kodama
et al., 2003). A subsequent study from this group has suggested that the mechanism by
which NK cells are activated is mediated through cytokines produced by antigenpresenting cells (Kodama et al., 2010).
Beta glucan from Grifola frondosa (Maitake) has recently been shown to enhance
umbilical cord blood stem cell transplantation (from full-term infants) in the nonobese
diabetic/severe combined immunodeficient (NOD/SCID) mouse. The Maitake beta glucan
(MBG) enhanced mouse bone marrow (BMC) and human umbilical cord blood (CB) cell
granulocyte-monocyte colony forming unit (GM-CFU) activity in vitro and protected GMCFU forming stem cells from doxorubicin (DOX) toxicity. MBG promoted a greater
expansion of CD34+CD33+CD38- human committed hematopoietic progenitor (HPC)
cells compared to the conventional stem cell culture medium. Oral administration of MBG
to recipient NOS/SCID mice led to enhanced homing at 3 days and engraftment at 6 days
in mouse bone marrow compared to control mice. More CD34+ human cord blood cells
were also retrieved from mouse spleen in beta glucan treated mice at 6 days after
transplantation. The studies suggest that Maitake beta glucan promoted hematopoiesis
through effects on CD34+ progenitor cell expansion ex vivo and when given to the
transplant recipient could enhance CD34+ precursor cell homing and support engraftment
(Lin et al., 2009a).
A study has also suggested that oral administration of a submerged cultivated G. frondosa
mixture, by normal mice, may enhance host innate immunity against foreign pathogens
without eliciting an adverse inflammatory response (Wang et al., 2008).
Anti-tumour activity induced by an extract from Grifola frondosa in a macrophage cell line,
RAW264.7 has been reported to be mediated via a nitric oxide-mediated pathway
(Sanzen et al., 2001). Similarly, an aqueous extract from Grifola frondosa has been
reported to have immuno-modulating properties via a mechanism involving the regulation
200
of nitric oxide (NO) production both in vivo and in vitro (Cao et al., 2006). A 23 kDa
polysaccharide isolated from Grifola frondosa, while not affecting the proliferation of colon26 cells in vitro, was shown to significantly inhibit tumour growth in BALB/cA mice
inoculated with colon-26 cancer cells, via activation of cell-mediated immunity (Masuda et
al., 2009).
The synergistic potentiation of interferon activity with Maitake mushroom on bladder
cancer cells has recently been reported (Louie et al., 2010). The combination of
interferon-alpha2b (10000 IU/mL) and Maitake mushroom D fraction (200 g/mL) reduced
growth by ~75% in T24 bladder cancer cells. This effect may be due to triggering doublestranded DNA-dependent protein kinase activation that may act on the cell cycle to cease
cancer cell growth.
The changes in the content of anti-tumour polysaccharides from Grifola frondosa during
storage have been investigated. When the mushrooms were stored at low temperature,
the content of the anti-tumour polysaccharides showed hardly any changes, but the
content decreased markedly at higher temperature (20C) (Mizuno, 2000).
A water-soluble extract of Grifola frondosa has been shown to inhibit the proliferation of
four human gastric cancer cell lines (TMK-1, MKN28, MKN45 and MKN74) in a timedependent manner. The inhibition was most pronounced in TMK-1 cells, which exhibited
up to 90% inhibition after treatment with 10% extract for 3 days. Induction of apoptosis
was confirmed by fluorescence-activated cell sorting analyses, while Western blot
analyses of TMK-1 cells after treatment with the extract revealed increases in
intracytoplasmic cytochrome c and cleavage of caspase-3 and poly(ADP-ribose)
polymerase, but no expression of p21 or Bax. The caspase-3 protease activities in lysates
of TMK-1 cells treated with 1% or 10% of the extract were approximately 3-fold higher
than in control cells. The data suggest that this extract from Grifola frondosa produces
potential antitumour effects on gastric cancer via an induction of apoptosis of TMK-1 cells
by caspase-3-dependent and -independent pathways (Shomori et al., 2009).
The photo-protective potential of exopolysaccharides (EPS) from Grifola frondosa HB0071
has been tested in human dermal fibroblasts (HDF) exposed to ultraviolet-A (UVA) light. It
was reported that EPS had an inhibitory effect on human interstitial collagenase (matrix
metalloproteinase, MMP-1) expression in UVA-irradiated HDF without any significant
cytotoxicity. The treatment of UVA-irradiated HDF with EPS resulted in a dose-dependent
decrease in the expression level of MMP-1 mRNA. The data suggested that EPS obtained
201
from a mycelial culture of Grifola frondosa HB0071 may contribute to an inhibitory action
in photo-ageing skin by reducing the MMP 1-related matrix degradation system (Bae et
al., 2005).
The biological function of GFPPS1b, a polysaccharide-peptide isolated from cultured
mycelia of Grifola frondosa GF9801, has been shown to suppress SGC-7901 cell growth
and reduce cell survival via arresting the cell cycle in the G(2)/M phase and inducing
apoptosis of tumour cells (Cui et al., 2007).
The potential anti-tumour effect of beta-glucan, a polysaccharide of the Maitake
mushroom, on human prostatic cancer PC-3 cells in vitro has been evaluated. The data
showed that a bioactive beta-glucan from the Maitake mushroom has a cytotoxic effect,
presumably through oxidative stress, on prostatic cancer cells in vitro, leading to
apoptosis. This mushroom polysaccharide may therefore have potential as a therapeutic
modality for prostate cancer (Fullerton et al., 2000). Maitake beta-glucan has also been
shown to induce hematopoietic stem cell proliferation (Lin et al., 2007).
A beta-glucan extracted from the fruiting body of Grifola frondosa has been reported to
activate cellular immunity and expresses anti-tumour effects, with the anti-tumour effects
relating to its control of the balance between T lymphocyte subsets Th-1 and Th-2. The
fraction decreased the activation of B cells and potentiated the activation of helper T cells,
resulting in enhanced cellular immunity. It also induced the production of interferon (IFN)gamma, interleukin (IL)-12 p70, and IL-18 by whole spleen cells and lymph node cells, but
suppressed that of IL-4. These results suggest that this fraction establishes Th-1
dominance which induces cellular immunity in the population that was Th-2 dominant due
to carcinoma (Inoue et al., 2002).
The anti-diabetic effect of an alpha-glucan (MT-alpha-glucan) from the fruit body of
Maitake mushrooms (Grifola frondosa) on KK-Ay mice (a type 2 diabetes animal model)
has been evaluated. Treatment with MT-alpha-glucan significantly decreased body
weight, level of fasting plasma glucose, glycosylated serum protein, serum insulin,
triglycerides, cholesterol, free fatty acid and malondialdehyde content in liver. Treatment
with MT-alpha-glucan significantly increased the content of hepatic glycogen, reduced
glutathione and the activity of liver superoxide dismutase and glutathione peroxidase.
Furthermore, the insulin binding capacity to liver crude plasma membranes increased and
histopathological changes in the pancreas were ameliorated in the treatment group. The
data suggested that MT-alpha-glucan has an anti-diabetic effect on KK-Ay mice, which
202
may be related to its effect on insulin receptors by increasing insulin sensitivity and
ameliorating insulin resistance of peripheral target tissues (Lei et al., 2007).
Enhanced insulin-hypoglycaemic activity (improvement in insulin sensitivity) has also been
reported in spontaneously hypertensive rats consuming a glycoprotein extracted from
Maitake mushrooms (Preuss et al., 2007).
The effect of Grifola frondosa total water extract on two osteoblastic cell cultures (HOS58
and SaOS-2) has been investigated to determine if this mushroom has osteo-inductive
properties. The activity of alkaline phosphate and mineralization were used as indicators
for the vitality and maturation of bone cells. The cultivation of human osteosarcoma cells
HOS58 for 5 days in the presence of an aqueous extract of G. frondosa resulted in a
significant elevation of alkaline phosphatase activity of the cells in comparison to
untreated cells. SaOS-2 cells, incubated with GFfor 21 days, showed a nearly two-fold
higher mineralization than cells cultured with a positive control, demonstrating the activity
of Grifola frondosa extract as a bone-inducing agent (Saif et al., 2007).
mushroom Maitake (Grifola frondosa) fiber. The results demonstrated that mushroom fiber
lowered the serum total cholesterol level by enhancement of the hepatic low density
lipoprotein (LDL) receptor mRNA (Fukushima et al., 2001).
Maitake mushroom consumption has also been shown, in Sprague-Dawley rats, to have
the ability to alter lipid metabolism by inhibiting both the accumulation of liver lipids and
the elevation of serum lipids. Further studies are needed to determine the mechanism of
activity of Maitake mushrooms and to establish whether their action in humans is similar to
that observed in the rat model (Kubo and Nanba, 1996). A further study by the same
group, using the same rat model system, has also shown that consumption of dried
Maitake powder (mixed with a basic high-cholesterol rat chow) cholesterol, triglyceride
and phospholipids in the serum of rats in the Maitake-feed group were suppressed by 0.30.8 times those in animals fed the basic feed.
Weights of liver and epididymal fat-pads were significantly lower (0.6-0.7 times) than
those in the basic feed group, indicating that Maitake inhibited lipid accumulation in the
body. Liver lipids were also measured and the values were found to be decreased by
Maitake administration. Measurement of the amount of total cholesterol and bile acid in
faeces showed the ratio of cholesterol-excretion had increased 1.8 fold and bile acid-
203
excretion 3 fold by Maitake treatment suggesting that Maitake consumption may help to
improve the lipid metabolism as it inhibits both liver lipid and serum lipids which were
increased by the ingestion of high-fat feed (Kubo and Nanba, 1997).
Blood pressure of spontaneously hypertensive rats (SHR) has been shown to be
significantly reduced by Maitake feeding for 8 weeks, beginning at a time when the
animals were 10 weeks of age with well-established high blood pressure. There was no
difference in the plasma total and free cholesterol, triglyceride and phospholipid levels
between the Maitake fed animals and the control (Kabir and Kimura, 1989).
A single oral dose of an extract of powdered Grifola frondosa, at dosage levels of 500 and
2,000mg/kg has been given to 5 Crj:CD(SD) IGS strain of rats of each sex for 1 day, and
its toxicity was examined. The control group was treated with water by injection. No
abnormal signs were noted in either sex of any group. No effects of powdered Grifola
Frondosa were reported in either sex by body weight measurement or necropsy finding
(Koike et al., 2003).
Hexane extracts of the cultured mycelia of Grifola frondosa have been shown to contain
ergosterol (1), ergostra-4,6,8(14),22-tetraen-3-one (2), and 1-oleoyl-2-linoleoyl-3palmitoylglycerol (3) and a fatty acid fraction containing palmitic, oleic, and linoleic acids.
The fatty acid fraction and compounds 1-3 showed cyclooxygenase (COX) enzyme
inhibitory and antioxidant activities. The inhibition of COX-1 enzyme by the fatty acid
fraction and compounds 1-3 at 250mg/mL were 98, 37, 55, and 67%, respectively.
Similarly, COX-2 enzyme activity was reduced by the fatty acid fraction and compounds 13 at 250mg/mL by 99, 37, 70, and 4%, respectively. The inhibition of liposome
peroxidation by the fatty acid fraction and compounds 1 and 2 at 100 mg/mL was 79, 48,
and 42%, respectively (Zhang et al., 2002).
An aqueous extract of Maitake (Grifola frondosa) mushrooms significantly reduced cellular
proliferation in MCF-7 human breast cancer cells by up to 33%. Maitake also significantly
induced apoptosis and cytotoxicity in these human breast cancer cells (Martin and
Brophy, 2010) with the activation of apoptosis possibly being mediated via BAK-1 gene
activation (Soares et al., 2011).
Mycelia from Grifola frondosa grown in the presence of non-mycotoxic concentrations of
100 and 200 ppm of Cu or 25 and 50 ppm of Zn accumulated 200-322 ppm and 267-510
ppm of Cu or Zn, respectively. When the enriched metal mycelia were subjected to a
204
simulated gastrointestinal digestion in vitro, the solubility in the digestive fluids was 642669 ppm and 102-530 ppm, which represent approximately 32-33% and 0.7-3.5% of the
recommended daily intake (RDI) for Cu and Zn, respectively, in 1 g of mycelium, with the
authors discussing potential uses of the mineral-enriched mycelia in capsules (in the case
of Cu-enriched mycelia) and in food preparations (Figlas et al., 2010).
Agaricoglycerides of the fermented mushroom Grifola frondosa at the dose level of 500
mg/kg has been shown to possess anti-inflammatory and antinociceptive effects in
preclinical animal models of inflammation and in some models of pain (Han and Cui,
2012).
Antioxidant properties and antioxidant compounds of various extracts from dried Grifola
frondosa (Maitake) have been determined. Antioxidant activity was measured using
reducing power, DPPH and superoxide radical scavenging and ferrous ion chelation
activity assays. Phenols, flavonoids, ascorbic acid and alpha-tocopherol were found to be
the major antioxidant components in the various mushroom extracts examined. The EC50
values (<20 mg/ml) indicate that the G. frondosa extracts studied have potent
antioxidative activity (Jan-Ying et al., 2011).
While granulocyte colony stimulating factor (G-CSF) treatment following chemotherapy is
effective in treating against bone marrow myelotoxicity, a beta-glucan extract from the
Maitake mushroom Grifola frondosa (MBG) has been shown to enhance colony forming
unit-granulocyte monocyte (CFU-GM) activity of mouse bone marrow and human
hematopoietic progenitor cells (HPC), and to stimulated G-CSF production. The study
showed that oral MBG promoted maturation of HPC to become functionally active myeloid
cells and enhanced peripheral blood leukocyte recovery after chemotoxic bone marrow
injury (Lin et al., 2010b).
A polysaccharide extracted from Grifola frondosa has been shown to induce cell-mediated
immunity by inducing bone marrow dendritic cell maturation and an antigen-specific Th1
response by enhancing dendritic cell-produced IL-12. Dedritic cells pulsed with colon-26
tumor lysate in the presence of the mushroom polysacchardide induced both therapeutic
and preventative effects on colon-26 tumor development in BALB/c mice (Masuda et al.,
2010). A further study from the same group has demonstrated that a soluble beta-(1,3)
(1,6)-glucan obtained from Grifola frondosa induced cell proliferation and cytokine
production without excessive inflammation in macrophages, supporting its
immunotherapeutic potential (Masuda et al., 2011).
205
Maitake mushroom extracts have been suggested to ameliorate progressive hypertension

in female Sprague-Dawley rats via an effect on systolic blood pressure that may, at least
in part, involve the renin-angiotensin system (Preuss et al., 2010).
The active compounds in Grifola frondosa (Maitake) and their effects have been reviewed
(Boh and Berovic, 2007).
Hericium erinaceum (Pom Pom, Lions Mane)
A human study of 30 females has investigated the

clinical outcomes of 4 weeks of intake of Hericium
erinaceus cookies versus placebo cookies on
menopause, depression, sleep quality and indefinite
complaints, using the Kupperman Menopausal Index
(KMI), the Center for Epidemiologic Studies
Depression Scale (CES-D), the Pittsburgh Sleep
Quality Index (PSQ1), and the Indefinite Complaints
Index (ICI). Each of the CES-D and the ICI score
after the H. erinaceus intake was significantly lower than at the start of the trial.
"Concentration", "irritating" and "anxious" tended to be lower than the placebo group
(Nagano et al., 2010, Shimizu et al., 2010). While the results point towards a possible
reduction of depression and anxiety in the study group with H. erinaceus intake, larger
studies with greater statistical power are required to confirm such outcomes.
Anti-dementia compounds have recently been reported from the mushroom Hericium
erinaceum (Kawagishi, 2007, Kawagishi and Zhuang, 2008). Hericium erinaceum extracts
have also been reported to induce neurite outgrowth from neural (NG108-15) cells.
Maximum stimulation of neurite outgrowth was recorded with mycelial extracts, and the
least stimulation was observed with an oven-dried fruit body extract. Aqueous extracts of
H. erinaceus therefore contain neuroactive compounds that stimulate neurite outgrowth in
vitro suggesting some value in the treatment of neurodegenerative disease (Wong et al.,
2007). The effects of Hericium erinaceus on amyloid beta (25-35) peptide-induced
learning and memory deficits in mice have evaluated. Mice were administered 10 g of
amyloid beta (25-35) peptide intracerebroventricularly on days 7 and 14, and fed a diet
206
containing H. erinaceus over a 23-d experimental period. Memory and learning function
was examined, with H. erinaceus preventing impairments of spatial short-term and visual
recognition memory induced by the amyloid beta(25-35) peptide (Mori et al., 2011).
Immuno-regulatory functions of Hericium erinaceum have been demonstrated in an
aqueous extract by a stimulation of inducible nitric oxide gene expression followed by
nitric oxide production in macrophages via enhancement of activation of the transcription
factor, NF-kappaB (Son et al., 2006).
Polysaccharides from Hericium erinaceum and Hericium laciniatum have been extracted
from culture broth and the polysaccharide components were mainly glucose in H.
erinaceus and galactose in H. laciniatum. Both polysaccharides had significant antiartificial pulmonary metastatic tumour effects in mice with the polysaccharide from H.
erinaceus being more effective than that from H. laciniatum. However, both of the
polysaccharides enhanced the increase of T cells and macrophages (immuno-enhancing
activity) (Wang et al., 2001).
The hypolipidemic effect of exo-polymers produced in submerged mycelial cultures of
Hericium erinaceus (HE), Auricularia auricula judae (AA), Flammulina velutipes (FV),
Phellinus pini (PP), and Grifola frondosa (GF) has been investigated in dietary-induced
hyperlipidemic rats. The animals were administered with exo-polymers at the level of
100mg/kg body weight daily for four weeks. A hypolipidemic effect was achieved in all the
experimental groups, however, HE exo-polymer proved to be the most potent, significantly
reducing plasma triglyceride (28.9%), total cholesterol (29.7%), low-density lipoprotein
(LDL) cholesterol (39.6%), phospholipid (16.0%), and liver total cholesterol (28.9%) levels,
compared to the saline administered (control) group. The results demonstrated the
potential of Hericium erinaceus exo-polymer in treating hyperlipidemia in dietary-induced
hyperlipidemic rat (Yang et al., 2003, Yang et al., 2002a).
A methanol extract of the fruiting bodies of Hericium erinaceus has been fed to rats and
shown to result in a significantly lower elevation rate of blood glucose level than control
rats. The effects on blood glucose, serum triglyceride and total cholesterol levels were
more significant in the rats fed daily with the Hericium erinaceus extract at doses of
100mg/kg body weight rather than 20mg/kg body weight (Wang et al., 2005).
207
Pretreatment with Hericium erinaceus (Bull.: Fr.) Pers. (Aphyllophoromycetideae) has also
been shown to reduce ulceration in ethanol-induced gastric ulcers in rats (Mahmood et al.,
2008).
In Sprague Dawley rats, an aqueous extract of the culinary-medicinal lion's mane mushroom,
Hericium erinaceus (Bull.: Fr.) pers. (Aphyllophoromycetideae) has been shown to accelerate
wound healing in rats (measured as less scar width at wound enclosure with the healed
wound containing fewer macrophages and more collagen with angiogenesis, compared to
wounds dressed with sterilized distilled H2O (Abdulla et al., 2011).
Aqueous extracts of Hericium erinaceus (17.7%) showed a relatively high Antioxidant
Index (% relative to quercetin) in vitro (Abdullah et al., 2012).
Treatment of mice with Hericium erinaceum (300 mg/kg for 14 days) prior to middle
cerebral artery (MCA) occlusion, protected against focal cerebral ischemia, by increasing
nerve growth factor levels, suggesting that H. erinaceum and its components could be
useful for preventing cerebral infarction (Hazekawa et al., 2010).
A study in mice has reported that consumption of either a hot water extract or ethanol
extract of Hericium erinaceus improved lipid metabolism in mice fed a high-fat diet.
Administration of either the water-extract or ethanol-extract with a high fat diet for 28 days
resulted in a marked decrease in body weight gain, fat weight as well as blood and
hepatic triacylglycerol levels (Hiwatashi et al., 2010).
It is interesting to note that aqueous and aqueous/ethanolic extracts of Hericium erinaceus
(Yamabushitake) mushroom were able to induce apoptosis in U937 human monocytic
leukemia cells, however, acidic and alkaline extracts with similar proximate compositions
were both inactive (Kim et al., 2011a). Hericium erinaceus mushroom-induced apoptosis
of U937 human monocytic leukemia cell has been reported to be via an effect on cell
proliferation that involves activation of mitochondria-mediated caspase-3 and caspase-9
but not caspase-8 (Sung Phil et al., 2011).
Antiproliferative and HIV-1 reverse transcriptase inhibitory activities have been
demonstrated from dried fruiting bodies of Hericium erinaceum (Li et al., 2010b).
208
Hypsizigus marmoreus (Buna-Shimeji)

Anti-tubercular activity and an inhibitory effect on
Epstein-Barr virus activation of sterols and
polyisoprenepolyols from an edible mushroom,
Hypsizigus marmoreus (Buna-shimeji) have been
reported. Seven sterols and eight
polyisoprenepolyols, isolated from the nonsaponifiable lipid fraction of the dichloromethane
extract of Hypsizigus marmoreus, have been tested for their anti-tubercular activity
against Mycobacterium tuberculosis strain H37Rv using the Microplate Alamar Blue Assay
(MABA). Six of the sterols and two of the polyisoprenepolyols showed a minimum
inhibitory concentration (MIC) in the range of 1-51 mg/ml, while the others were inactive.
The seven sterols and three polyisoprenepolyols were further evaluated for their inhibitory
effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by the tumour
promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells. Two of the sterols
showed a potent inhibitory effect while preserving the high viability of the Raji cells
(Akihisa et al., 2005).
Anti-tumour-promoting activity has been found in methanol and ethyl acetate extracts of
the mushroom 'Buna-shimeji', Hypsizigus marmoreus (Tricholomataceae). From the active
fractions of the extracts, two sterols, ergosterol and ergosterol peroxide, were isolated.
The isolates showed inhibitory activity against 12-O-tetradecanoylphorbol-13-acetate
induced ear inflammation in mice, and ergosterol markedly inhibited tumour promotion in a
two-stage carcinogenesis experiment (Yasukawa et al., 1994).
Aqueous and methanol extracts of Hypsizigus marmoreus have been tested against
allogeneic tumour, solid sarcoma 180 and syngeneic tumour and Meth A fibrosarcoma.
The aqueous extract was highly active in inhibiting growth of solid sarcoma 180, but not
as effective for Meth A fibrosarcoma. Fractionation of anti-tumour substances of the
aqueous extract isolated four polysaccharides. Chemical analysis revealed one of them to
be beta-(1-3)-glucan with a significant inhibitory effect against tumour-growth of sarcoma
180 (Ikekawa et al., 1992).
Chloroform extracts of the fruit bodies of Hypsizigus marmoreus have been shown to
exhibit moderate cytotoxicity towards cultured human colon carcinoma (HT-29), human
209
breast carcinoma (MCF-7) and human hepatoblastoma (HepG-2) cell lines (Xu et al.,
2007).
Anti-proliferative activities of fractions of Hypsizigus marmoreus have been examined
using HepG2 cells in vitro. The methanol extract of H.marmoreus markedly induced antiproliferative activity and an active compound from this mushroom has been identified as
hypsiziprenol A9. Hypsiziprenol A9 inhibited cell proliferation in a time- and concentrationdependent manner by up to 80% on HepG2 cells by inducing arrest of the G1 phase.
Hypsiziprenol A9 also decreased expression of phosphorylated retinoblastoma protein
(ppRb), cyclin D1, and cyclin E in a dose-dependent manner. The results suggested that
hypsiziprenol A9 can inhibit the growth of HepG2 cells through inducing G1 phase cell
cycle arrest due to the inhibition of pRb phosphorylation (Chang et al., 2004).
A novel ribonuclease, from fresh fruiting bodies of Hypsizigus marmoreus,with antiproliferative activity against the L1210 leukemia cell line has also been purified (Guan et
al., 2007). A thermostable ribosome-inactivating protein with a molecular weight of 20kDa,
isolated from fruiting bodies of Hypsizigus marmoreus has also been shown to have antiproliferative activity against mouse leukemia cells and human leukemia and hepatoma
cells (Lam and Ng, 2001).
The antioxidant effects of Hypsizygus marmoreus have been studied for peroxyl and
alkoxyl radicals by ordinary, non-tumour-bearing and tumour-bearing mice. Oral
administration of the fruit body of H. marmoreus exhibited potent anti-tumour or cancerpreventive effects and caused a significant decrease in lipid peroxide levels, which were
determined as thiobarbituric acid reactive substances. These results showed that the
intake of H. marmoreus fruit body could induce an antioxidant effect, and the increase of
antioxidant activity in the plasma of tumour-bearing mice was an important mechanism in
cancer prevention. It was also suggested that the mushroom might play a role in the
decrease of lipid peroxides through antioxidant activity induction (Matsuzawa, 2006).
conditioned medium of human peripheral blood mononuclear cells stimulated with coldwater extracts (10-800 mg/mL of medium) of Hypsizigus mamoreus, Agrocybe aegerite
and Flammulina velutipes (Ou et al., 2005).
The isolation of a collagen-binding protein from Hypsizigus marmoreus, which inhibits the
Lewis lung carcinoma cell adhesion to type IV collagen has been reported. A type IV
210
collagen-binding protein of 23kDa was isolated from the mushroom, Hypsizigus

marmoreus. This protein, HM 23, bound to type IV and type I collagens and gelatin, and to
much lesser extent to fibronectin, but not to laminin or bovine serum albumin. The
adhesion of Lewis lung carcinoma cells was inhibited when the type IV collagen
substratum was pretreated with HM 23 (Tsuchida et al., 1995).
Bunashimeji-related hypersensitivity pneumonitis has been reported in workers who
cultivate this mushroom in indoor facilities in Japan. An evaluation of protective measures
concluded that complete cessation was the best treatment for hypersensitivity
pneumonitis. The use of a mask was ineffective for patients with a high serum Krebs von
der Lungen-6 (KL-6), surfactant protein-D (SP-D) concentration and severe ground-glass
opacity on chest high-resolution computed tomography. Initial treatment with oral
prednisolone was recommended for patients with high levels of total cell counts in
bronchoalveolar lavage fluid (Tsushima et al., 2006).
Water-soluble extracts isolated from Hypsizigus marmoreus have been shown to
significantly stimulate Raw 264.7 cancer cells to release nitric oxide (NO) and
prostaglandin E(2), suggesting their potential immunomodulating activities (Bao and You,
2011). A further study from the same group has subsequently also shown that alkalisoluble proteoglycans and acid-soluble proteoglycans from Hypsizygus marmoreus
significantly stimulated Raw264.7 cells to release nitric oxide, prostaglandin E2 as well as
cytokines, such as IL-1 beta, TNF-alpha and IL-6 by inducing mRNA expression (Bao et
al., 2012).
An extract from Hypsizygus marmoreus has also been shown to inhibit platelet
aggregation induced by collagen suggesting that it may have an effect against platelet
related cardiovascular disease (Park et al., 2011).
211
Inonotus obliquus (Chaga)

Anticancer activity of sub-fractions containing 3 betahydroxy-lanosta-8,24-dien-21-al, inotodiol and
lanosterol, of the Chaga mushroom (Inonotus
obliquus) against human cancer cells and in Balbc/c
mice bearing Sarcoma-180 cells has been reported.
All of the subtractions isolated from I. obliquus
showed significant cytotoxic activity against the
selected cancer cell lines (lung carcinoma A-549
cells, stomach adenocarcinoma AGS cells, breast adenocarcinoma MCF-7 cells, and
cervical adenocarcinoma HeLa cells) in vitro. Subfraction I (3 beta-hydroxy-lanosta-8,24dien-21-al,) isolated from I. obliquus showed greater inhibition of tumor growth than
subtractions 2 and 3 (inotodiol and lanosterol) which agreed well with the in vitro results
(Chung et al., 2010).
Cognitive enhancing and antioxidant activities of Inonotus obliquus (Chaga) have been
evaluated against scopolamine-induced experimental amnesia in mice. A methanol
extract of Chaga (MEC) at 50 and 100 mg/kg doses was administered orally for 7 days to
amnesic mice. To elucidate the mechanism of the cognitive enhancing activity of MEC,
the activities of acetylcholinesterase (AChE), anti-oxidant enzymes, the levels of
acetylcholine (ACh) and nitrite of mice brain homogenates were evaluated. MEC
treatment for 7 days significantly improved the learning and memory. The significant
cognitive enhancement observed in mice after MEC administration was closely related to
higher brain anti-oxidant properties and inhibition of AChE activity (Giridharan et al.,
2011).
Leccinum extremiorientale
Two sterols isolated from the edible mushroom Leccinum
extremiorientale have been shown to suppress the formation
of osteoclasts and thereby may have some value in the
treatment of osteoporosis (Choi et al., 2010).
212
Lentinula edodes (Shiitake)
A clinical trial in 30 volunteers has been undertaken over 11

days in which a low molecular mass fraction of an aqueous
extract of Lentinus edodes (Shiitake) was evaluated as an
oral mouthrinse. The mushroom extract was evaluated
against Listerine and a placebo (water). Statistically
significant differences were obtained for the plaque index on
day 12 in subjects treated with mushroom versus placebo,
while for the gingival index significant differences were found
for both mushroom versus placebo and mushroom versus
Listerine. Decreases in total bacterial counts and in counts of specific oral pathogens were
observed for both mushroom extract and Listerine in comparison with placebo. The data
suggest that this mushroom extract may prove beneficial in controlling dental caries
and/or gingivitis/periodontitis (Signoretto et al., 2011). A fraction from Shiitake has also
been shown to have a strong inhibiting effect on dentin demineralization and induce
microbial shifts that could be associated with oral health (Zaura et al., 2011).
The effect and safety of a soluble beta-glucan from Lentinus edodes mycelium, Lentinex
(R), in 42 healthy, elderly subjects has recently been evaluated in a double blind,
crossover, placebo-controlled trial (Gaullier et al., 2011) where two groups were given
either 2.5 mg/day Lentinex (R) orally or placebo for 6 weeks; then after a washout period
of 4 weeks, the alternate supplementation was given for 6 weeks. The changes in the
number of B-cells were significantly different between the groups. The number of NK cells
increased significantly in both groups, but there was no significant difference between the
groups. The immunoglobulins, complement proteins and cytokines measured were not
altered. The safety blood variables (differential cell count, liver function, kidney function,
and other blood chemistry) were not influenced by Lentinex (R), and the number, nature,
and severity of adverse events were similar to placebo. Lentinex given orally to elderly
subjects was deemed to be safe and induced an increase in the number of circulating Bcells (Gaullier et al., 2011).
The European Food Safety Authority (EFSA) has recently carried out a safety assessment for
Lentinex, an aqueous mycelial extract of Lentinula edodes (Shiitake mushroom), as a novel
food ingredient in the context of Regulation (EC) No 258/97. Lentinex consists of
approximately 98 % water and 2 % dry matter (beta-glucan lentinan, free glucose and N-
213
containing constituents). The proposed intake of 2.5 mL Lentinex containing 1 mg lentinan

(beta-glucan)/mL corresponds to 41.7 mug/kg body weight for a 60 kg person. The intake of
beta-glucan resulting from the proposed use is low compared to the intake estimated from the
consumption of the mushroom Lentinula edodes and of other beta-glucan sources. The
animal and human studies provided by the applicant to EFSA were primarily carried out to
determine the efficacy of the novel food ingredient; they were supporting but of limited value
regarding a safety assessment. Owing to the fermentative production of the novel food
ingredient from the mycelium and the final application of a heat-induced sterilisation step in
various food products, adverse effects reported after the consumption of the fruiting body of
the Shiitake mushroom were not considered relevant. Although an allergenic risk cannot be
excluded for sensitive subjects, EFSA concluded that such a risk was expected not to be
higher than that resulting from the normal consumption of the fruiting body of Lentinula
edodes. EFSA noted the presence of soy peptides in the culture medium. The safety of
Lentinex as a novel food ingredient was established at the proposed conditions of use and the
proposed levels of intake (EFSA Panel on Dietetic Products and Allergies, 2010).
Extracts from Lentinula edodes (Shiitake) have been widely reported to have anti-tumour
activity. However, this activity has been shown to be host-mediated and not by direct
cytotoxic activity to cancer cells. A recent study (Israilides et al., 2008) has now
demonstrated cytotoxic and cell growth inhibitory (cytostatic) effects of aqueous extracts
of the mushroom on the MCF-7 human breast adenocarcinoma cell line. The effect was
demonstrated with fruit body and mycelial extracts, the difference being that there was no
significant suppression on normal cells with the latter. Furthermore, mycelial extracts did
not induce any cytostatic effect in both cancer and normal cell lines based on a DNA
synthesis assay. The significant suppression of the proliferation of cancer cells was
reflected by the comparatively low IC50 values and the simultaneous higher respective
values on normal fibroblast cells. In addition to the direct inhibition of the proliferation of
human breast cancer cells in vitro, the Lentinula edodes extract had immunostimulatory
properties in terms of mitogenic and co-mitogenic activity in vitro.
Protein extracts of Lentinus edodes C91-3 fermentation broth administered to mice with
cervical cancer prolonged the lifespan of tumour-bearing mice significantly and killed
cervical cancer U14 cells in vitro. (Liu et al., 2009).
The effects of diets containing dry powdered Shiitake mushroom on frequency of
azoxymethane-induced colon aberrant crypt foci (ACF) and intestinal tumours in male
Sprague-Dawley rats have been studied. Pregnant rat dams and their progeny were fed
214
AIN-93G diets containing casein (20%; control diet) or casein supplemented with Shiitake
(1% or 4% wt/wt). Casein- and 1% Shiitake-fed rats exhibited identical growth curves,
whereas those fed the 4% Shiitake diet were of slightly reduced body weight. The 4%
Shiitake diet elicited increased active energy expenditure and reduced adiposity of rats.
Small bowel and colon tumours and colon ACF were evaluated in the male progeny at 18
weeks after azoxymethane treatment. Aberrant crypt foci and tumours were most
prevalent in the mid and distal regions of the colon. Shiitake intake had no effect on the
relative incidence of tumours in the colon or small intestine (duodenum). Consumption of
1% Shiitake stimulated growth of invasive adenocarcinomas in the mid colon and
favoured a non-significant increase in median frequency of ACF in this same region. In
contrast, Shiitake at 4% intake elicited a reduction in colon tumour multiplicity. The
authors suggested a stimulatory action of 1% Shiitake on rat colon tumourigenesis which
is puzzling as the data were not statistically significant. However, the inhibitory actions of
4% Shiitake mushroom on the indices of rat colon tumourigenesis where statistically
validated (Frank et al., 2006).
Shiitake extracts have been dispersed with lecithin micelles to prepare superfine particles
(0.05 to 0.2 microns in diameter) of beta-1,3-glucan (micellary mushroom extracts). When
mice were fed with these micelles of beta-glucan (0.75mg/day/mouse, smaller amounts of
beta-glucan), the number of lymphocytes yielded by the small intestine increased by up to
40% and tumour cytotoxicity against P815 cells and cytokine production was also
augmented, suggesting that smaller amounts of micellary beta-glucan might be useful for
the potentiation of intestinal immunity (Shen et al., 2007). The Shiitake mushroom-derived
immuno-stimulant lentinan has also been reported to protect against murine malaria
blood-stage infection by evoking adaptive immune-responses (Zhou et al., 2009).
The effects of protein-bound polysaccharides (A-PBP and L-PBP), extracted from the
mycelia of Agaricus blazei and Lentinus edodes, on serum cholesterol and body weight
have been investigated in 90 female volunteers. The data demonstrated a weightcontrolling and hypolipidemic effect of both A-PBP and L-PBP via a mechanism involving
absorption of cholesterol (Kweon et al., 2002).
The effect of Shiitake (Lentinus edodes, LE) and autolyzed- (fermented-) Shiitake
(autolyzed-LE) on blood pressure and serum fat levels of spontaneously hypertensive rats
(SHR) have been studied. The animals of the autolyzed-LE group showed significantly
lower blood pressure compared to the control or LE group. The serum levels of total
cholesterol (TC), triglyceride and phospholipid of the groups fed with LE and autolyzed-LE
215
were lower than those of the control group, and atherogenic index [(TC-HDL-C)/HDL-C]
improved significantly in 21 days. It was suggested that the serum TC decline is the action
of eritadenine that is contained in the Shiitake mushroom. An inhibitory activity of the
angiotensin I-converting enzyme (ACE) was compared between of LE and autolyzed-LE.
Autolyzed-LE showed higher inhibitory activity than LE against the ACE. The results
suggested that the hypotensive action of autolyzed-LE was due to concomitant ACE
inhibitory activities of peptides and gamma-aminobutyric acid contained in higher amounts
during the autolysis of LE (Watanabe et al., 2002).
The changes in the content of an anti-tumour polysaccharide from Lentinus edodes
(lentinan) during storage have been investigated. When the mushrooms were stored at
low temperature, the content of their anti-tumour polysaccharides showed hardly any
changes, but the content decreased markedly at higher temperature (20C) (Mizuno,
2000).
The Shiitake mushroom (Lentinus edodes) contains the hypocholesterolemic agent
eritadenine, 2(R),3(R)-dihydroxy-4-(9-adenyl)-butyric acid. A study has recently been
conducted to quantify the amount of the cholesterol reducing agent eritadenine in Shiitake
mushrooms. The amounts of eritadenine in the fruit bodies of four different shiitake
mushrooms, Le-1, Le-2, Le-A, and Le-B, were investigated. Methanol extraction was used
to recover as much eritadenine as possible from the fungal cells, and enzymes that
degrade the fungal cell walls were also used to elucidate if the extraction could be further
enhanced. The Shiitake strains under investigation exhibited up to 10-fold higher levels of
eritadenine than previously reported for other Shiitake strains. Pre-treatment of
mushrooms with hydrolytic enzymes before methanol extraction resulted in an
insignificant increase in the amount of eritadenine released. The results suggested the
potential for delivery of therapeutic amounts of eritadenine from the ingestion of extracts
or dried concentrates of Shiitake mushroom strains (Enman et al., 2007).
mushroom Shiitake (Lentinus edodes) fiber. The results demonstrated that mushroom
fiber lowered the serum total cholesterol level by enhancement of the hepatic low density
lipoprotein (LDL) receptor mRNA (Fukushima et al., 2001).
Methanol and water extracts from Lentinus edodes have been shown to have antioxidant
activity against lipid peroxidation of rat brain homogenate. The antioxidant activity against
216
lipid peroxidation was found to correlate with the phenolic content in different sub-fractions
of the mushroom extracts (Cheung and Cheung, 2005).
The effect of heat treatment on the changes in the overall antioxidant activity and
polyphenolic compounds of Shiitake extract has been investigated. Raw Shiitake was
heated at 100 and 121C for 15 or 30 min using an autoclave. After heat treatment, the
free and bound polyphenolics and flavonoids in the mushroom extracts were analyzed.
2,2-Azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical and 1,1-diphenyl-2picrythydrazyl (DPPH) radical scavenging activities were measured to evaluate
antioxidant activity of the extracts. The polyphenolic contents and antioxidant activities in
the extracts increased as heating temperature and time increased. The free polyphenolic
content in the extract heated at 121C for 30 min was increased by 1.9-fold compared to
that in the extract from the raw sample. The ABTS and DPPH radical scavenging activities
were increased by 2.0-fold and 2.2-fold compared to the raw sample, respectively. The
data showed that heat treatment significantly enhanced the overall antioxidant activities of
Shiitake mushrooms (Choi et al., 2006a).
High-molecular-weight polysaccharides (HMWP), including lentinan, in Shiitake
mushrooms may promote human health. A study has been conducted to determine if
management protocols influence the HMWP of Shiitake (Lentinula edodes (Berk.) Pegler)
mushrooms. The results indicated that measuring the total carbohydrate content of waterextractable, ethanol-insoluble polysaccharides was a simple way to estimate HMWP. The
results also indicated that log-grown Shiitake contained more HMWP than did substrategrown Shiitake. Among log-grown Shiitake, both mushroom strain and tree species
influenced HMWP content. The results suggested that there is considerable variation
among Shiitake mushrooms in HMWP content and that production protocols influenced
the HMWP content of mushrooms (Brauer et al., 2002).
Supplemental amounts of a polysaccharide/oligosaccharide complex obtained from a
Shiitake mushroom extract have been evaluated for the ability to lower the prostatespecific antigen level in patients (n=62) with prostate cancer. The data showed that the
Shiitake mushroom extract alone was ineffective in the treatment of clinical prostate
cancer (White et al., 2002). A high genistein, Shiitake mushroom extract has also been
reported to have anti-tumour effects on prostate cancer (Hackman et al., 2001).
An ethyl acetate fraction from Shiitake (Lentinus edodes) mushrooms has been
investigated using two human breast carcinoma cell lines (MDA-MB-453 and MCF-7), one
217
human non-malignant breast epithelial cell line (MCF-10F), and two myeloma cell lines
(RPMI-8226 and IM-9). Concentration-dependent anti-proliferative effects of the fraction
were observed in all cell lines. Approximately 50mg/L of the fraction induced apoptosis in
50% of the population of four human tumour cell lines and the fraction-induced apoptosis
may have been mediated through the pro-apoptotic bax protein which was up-regulated.
Cell cycle analysis revealed that the fraction induced cell cycle arrest by a significant
decrease of the S phase, which was associated with the induction of cdk inhibitors (p21)
and the suppression of cdk4 and cyclin D1 activity. Compared to malignant tumour cells,
non-malignant cells were less sensitive to the fraction for the suppression of cell growth
and regulation of bax, p21, cyclin D1, and cdk4 expression. A 51% anti-proliferative effect
occurred at the highest concentration of the fraction (800mg/L). The data suggest that
inhibition of growth in tumour cells by the Shiitake mushroom extract may result from an
induction of apoptosis (Fang et al., 2006).
The isolation and characterization of an anti-tumour polysaccharide, KS-2, extracted from
culture mycelia of Lentinus edodes has also been reported. KS-2 suppressed the growth
of EHRLICH as well as Sarcoma-180 tumours in mice when given either orally or
intraperitoneally (Fujii et al., 1978).
Extracts from fermentation broth and mycelium of 15 strains of Lentinus edodes have
been shown to be active against gram positive and gram negative bacteria, yeasts and
mycelial fungi, including dermatophytes and phytopathogens. The strains differed by the
set of the organisms susceptible to the action of the extracts. Strains of L. edodes
combining marked anti-bacterial properties and high yields of water soluble
polysaccharides were screened. The active compounds were detected by preparative thin
layer chromatography. Two were identified with UV- and mass spectrometry as
lentinamycin B and erytadenine (lentinacin). Lentinamycin B was found to be the main
component responsible for the anti-bacterial activity of the L. edodes strains (Soboleva et
al., 2006).
The anti-microbial activity of the culture fluid of Lentinus edodes mycelium grown in
submerged liquid culture has been demonstrated against Streptococcus pyogenes,
Staphylococcus aureus and Bacillus megaterium. The substance responsible for the
activity was heat-stable and was suggested to be lenthionine, an anti-bacterial and antifungal sulphur-containing compound (Hatvani, 2001).
218
A study on the action of lentinan (extracted from Shiitake mushrooms (Lentinus edodes)
has been conducted using murine lymphoma (K36) cells in a AKR mouse model. Further
investigation on the effectiveness of the extracted lentinan was then performed using
human colon-carcinoma cell lines in mice. Six established human colon-carcinoma cell
lines segregated into three groups of different degrees of differentiation were used in this
study. One group was not fed (control) and the second group was prefed with lentinan for
7 days prior to inoculations with the cancer cells. The size of the tumours that developed
was rated after 1 month. Significant regression in tumour formation was observed in
prefed mice compared to control (unfed) mice when K36 or human colon-carcinoma cells
were used. Significant reductions in the size of the tumours were observed in mice prefed
with lentinan. Follow-up investigation proceeded with the use of nude mice (athymic).
Lymphocytes extracted from AKR mice prefed with lentinan for 7 days were inoculated
into the nude mice. This was then followed by inoculation of the human colon-carcinoma
cell lines into these mice. Much smaller tumours were formed in nude mice inoculated with
lymphocytes, in contrast to the larger tumour formed in nude mice without lymphocyte
inoculation. The study concluded that the anti-tumour property of lentinan was maintained
with oral administration. In addition, "primed" lymphocytes, when given passively to
immuno-deficient mice, were able to retard the development of tumours in these mice (Ng
and Yap, 2002).
The hypoglycemic effect of exo-polymers (EPs) produced from submerged mycelial
cultures of five varieties of mushrooms on streptozotocin (STZ)-induced diabetic rats have
been investigated. The five experimental groups were fed with EPs (50mg/kg body
weight) for 7 days. Significant reductions in plasma glucose, total cholesterol (TC), and
triglyceride (TG) levels were observed in rats fed with Lentinus edodes and Cordyceps
militaris EPs. Plasma glucose and TC were also reduced by administration of Phellinus
linteus EPs, but the TG level was not changed significantly. The EPs of the three
mushroom species also demonstrated a marked reduction in the level of plasma
glutamate-pyruvate transaminase (GPT). The result demonstrated the hypoglycemic
activity of EPs of three mushroom varieties in STZ-induced diabetic rats and suggests
some potential in the control of diabetes mellitus (Kim et al., 2001).
A subsequent study by the same group, using higher concentrations (200mg/kg body
weight in streptozotocin-induced diabetic rats) of exo-polymers from a submerged
mycelial culture of Lentinus edodes has shown that the administration of the exo-polymer
reduced the plasma glucose level by as much as 21.5%, and increased plasma insulin by
219
22.1% compared to the control group. It was also shown to lower the plasma total
cholesterol and triglyceride levels by 25.1 and 44.5%, respectively (Yang et al., 2002c).
Three anti-bacterial compounds extracted by chloroform, ethylacetate or water from dried
Shiitake mushrooms (Lentinus edodes) have been reported which possessed efficient
anti-bacterial activities against Streptococcus spp., Actinomyces spp., Lactobacillus spp.,
Prevotella spp., and Porphyromonas spp. of oral origin. In contrast, other general bacteria,
such as Enterococcus spp., Staphylococcus spp., Escherichia spp., Bacillus spp., and
Candida spp. were relatively resistant to these compounds. The anti-bacterial activity of
chloroform extracts and ethylacetate extracts were relatively heat-stable, while the water
extract was heat-labile (Hirasawa et al., 1999).
The action of the juice of Shiitake mushrooms (L. edodes) at a concentration of 5% from
the volume of the nutrient medium was found to produce a pronounced anti-microbial
effect with respect to Escherichia coli O-114, Staphylococcus aureus, Enterococcus
faecalis, Candida albicans and to stimulate the growth of E. coli M-17. Bifidobacteria and
Lactobacteria exhibited resistance to the action of L. edodes juice (Kuznetsov et al.,
2005).
Shiitake dermatitis after the ingestion of raw Shiitake mushrooms has been reported,
primarily in Japan, and it has been suggested that this dermatitis may be photosensitive
as nearly half of the patients studied developed the dermatitis on skin exposed to sunlight
(Hanada and Hashimoto, 1998). A study in Korea has also reported dermatitis effects, but
in contrast to the previous reports in Japan, cases with Shiitake dermatitis occurred after
eating boiled or cooked Shiitake mushrooms suggesting that a non-thermolabile
factor/component may be involved (Ha et al., 2003).
A study has been conducted with 10 people where each participant ingested 4g of
Shiitake powder daily for 10 weeks (trial 1), and the protocol was repeated in the same
subjects after 3 to 6 months (trial 2). Gastrointestinal symptoms coincided with
eosinophilia in two subjects. Symptoms and eosinophilia resolved after discontinuing
Shiitake ingestion. The authors reported that daily ingestion of Shiitake mushroom powder
in five of 10 healthy persons provoked blood eosinophilia, increased eosinophil granule
proteins in serum and stool, and increased gastrointestinal symptoms (Levy et al., 1998).
A single oral dose of an extract of cultured Lentinus edodes mycelia, at dosage levels of
500 and 2,000mg/kg has been given to 5 Crj:CD(SD) IGS strain of rats of each sex for 1
220
day, and its toxicity was examined. The control group was treated with water by injection.
No abnormal signs were noted in either sex of any group. No effects of Lentinus edodes
mycelia were reported in either sex by body weight measurement or necropsy finding
(Koike et al., 2002a). A follow on study by the same authors that extended the treatments
for 28 days reported no effects in either sex by body weight measurement, food
consumption measurement, urinalysis, ophthalmological examination, hematological
examination, blood chemical analysis, necropsy finding, organ weight measurement, or
histopathological examination (Koike et al., 2002b).
Low molecular mass (LMM) fractions from extracts of Shiitake mushrooms (as well as
from raspberry and red chicory) have been shown to be a useful source of specific
antibacterial, antiadhesion/coaggregation, and antibiofilm agent(s) that may be used for
protection towards caries and gingivitis. Each of the LMM fractions tested prevented or
reduced the induction of gene expression of the periodontal pathogens Prevotella
intermedia and Actinomyces naeslundii, suggesting that these LMM fractions could
modulate the effects of bacteria associated with periodontal disease in gingival cells
(Canesi et al., 2011). Furthermore, a study has compared the effectiveness of Shiitake
mushroom extract against the active component in a leading gingivitis mouthwash,
containing chlorhexidine, in an artificial mouth model (constant depth film fermenter). The
total bacterial numbers as well as numbers of eight key taxa in the oral environment were
investigated over time. The results indicated that Shiitake mushroom extract lowered the
numbers of some pathogenic taxa without affecting the taxa associated with health, unlike
chlorhexidine which had a limited effect on all taxa (Ciric et al., 2011).
The toxicological safety of an extract from cultured Lentinula edodes mycelia (L.E.M.) has
been determined using repeated doses (2,000 mg/kg/day) to male and female Wistar rats for
28 days. No mortality or abnormality in the general status or appearance was observed in rats
administered L.E.M extract. The study reported no clinically significant changes related to
toxicity. The no observed adverse effect level (NOAEL) of L.E.M. extract was considered to be
more than 2,000 mg/kg/day (Yoshioka et al., 2010).
221
effects. It should be noted however, that another study has suggested that supplementing
a mouse diet with 5% SM can result in a fatty liver (an elevation in IL-6 is also implicated
in fatty liver disease), but 15 days post withdrawal of SM, liver histology was completely
normalized. This effect of SM was not seen with WBM consumption (Chandra et al.,
2011b).
Supplementation of rats on a high fat diet with Shiitake Mushroom (Lentinus edodes)
powder resulted in negative correlations between the amount of Shiitake mushroom
supplementation and body weight gain, plasma triglyceride, and total fat mass (Handayani
et al., 2011)
Strong antioxidant properties have recently been described for a water-extractable
polysaccharide fraction from Lentinus edodes (Shiitake) (Chen et al., 2012a).
The responses of human oral squamous cell carcinoma (OSCC) cells to Lentinan, beta-(1
-> 3)-D-glucan, an extract from Lentinus edodes (0.1 mg/kg/day, 2 times/week), alone and
in combination with S-1, an oral antineoplastic agent that can induce apoptosis in various
types of cancer cells (6.9 mg/kg/day, 7 times/week)has been studied using a nude mouse
xenograft model. Combined therapy of Lentinan and S-1 markedly exerted antitumor
effects on human OSCC xenografts and significantly induced apoptotic cells in tumors
treated with Lentinan plus S-1, with no loss of body weight being observed in mice treated
with the combined therapy (Harada et al., 2010).
The phenolic compounds, syringic acid and vanillic acid from Lentinula edodes mycelia
that have radical scavenging activity, have also been shown to have a hepatoprotective
effect on CCl4--induced liver injury in mice. The intravenous administration of syringic acid
and vanillic acid significantly decreased the levels of the transaminases, suppressed
collagen accumulation and significantly decreased hepatic hydroxyproline content, which
is the quantitative marker of fibrosis. Both of these compounds inhibited the activation of
cultured hepatic stellate cells, which play a central role in liver fibrogenesis, and
maintained hepatocyte viability. Syringic and vanillic acid may therefore play a role in the
suppression of hepatic fibrosis in chronic liver injury (Itoh et al., 2010).
222
Letinus edodes has been shown to have immunomodulating effects which are mediated
via the enhancement of type-1 helper T cell-mediated cellular immunity (Hyun Ji et al.,
2011). Intake of Lentinula edodes mycelia extract significantly inhibited tumor growth in
C57BL/6 mice inoculated with B16 melanoma, and this in vivo anti-tumor effect was not
observed in nude mice, suggesting a T cell-dependent mechanism. Oral ingestion of
Lentinula edodes extract restored immune responses of class I-restricted and melanomareactive CD8(+) T cells in these melanoma-bearing mice, possibly via a mitigation of T
cell-mediated immunosuppression (Tanaka et al., 2011).
Lentinan, a cell wall beta-glucan from the fruiting bodies of Lentinus edodes has been
reported to exert its immunomodulating activity (in RAW 264.7 macrophages) by
activation of MAPK signaling pathways without secretion of TNF-alpha and NO (Xu et al.,
2011a).
The effects of a beta-glucan supplement (Lentinan) from Lentula edodes (Shiitake) on BN
rats have been studied and in a preclinical model of acute myeloid leukemia. BN rats
supplemented daily with lentinan exhibited weight gains, increased white blood cells,
monocytes and circulating cytotoxic T-cells, and had a reduction in anti-inflammatory
cytokines IL-4, IL-10, and IL-6. A combination of lentinan with standards of care in acute
myeloid leukemia, idarubicin, and cytarabine increased average survival compared with
monotherapy and reduced cachexia suggesting that nutritional supplementation of cancer
patients with lentinan would warrant investigation (McCormack et al., 2010).
A laccase with HIV-1 reverse transcriptase inhibitory activity has recently been isolated
from fresh fruiting bodies of Lentinus edodes (Shiitake)(Sun et al., 2011)
The effects of Active Hexose Correlated Compound (AHCC) from Lentinula edodes and its
use as a complementary therapy in patients with cancer has recently been reviewed (Shah et
al., 2011), as have the pharmacological activity and therapeutic applications of Lentinus
edodes (Bisen et al., 2010).
223
Lyophyllum connatum
A new ergothioneine derivative, beta-hydroxyergothioneine
has been isolated from the mushroom Lyophyllum connatum.
Ergothioneine, N-hydroxy-N',N'-dimethylurea, and connatin
(N-hydroxy-N',N'-dimethylcitrulline) were also isolated. All the
compounds displayed the ability to scavenge free radicals,
based on a 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical
scavenging assay. Structural determination, including the
absolute stereochemistry of beta-hydroxyergothioneine, was
achieved by spectroscopic analysis and X-ray
crystallography. The radical scavenging activity of betahydroxyergothioneine was almost the same as that of ergothioneine. Betahydroxyergothioneine showed the greatest protective activity against carbon tetrachlorideinduced injury in primary culture hepatocytes (Kimura et al., 2005).
Phellinus igniarius
Oral administration of an endo-polysaccharide of
Phellinus igniarius inhibited the growth of Sarcoma
180 and Hepatoma 22 cells that were implanted in
mice, and increased the life span. Serum IL-2 and
IL-18 were significantly increased in the Sarcoma
180 implanted mice fed with the endopolysaccharide at 500 mg/kg and 250 mg/kg
compared with those in control. The concentrations of serum IL-2 only were significantly
increased in Hepatoma 22 implanted mice using the same doses (Chen et al., 2011b),
suggesting that the anti-tumor effect was mediated via enhancement of cell mediated
immunity.
Hispolon, an active phenolic compound of Phellinus igniarius, induces apoptosis and cell
cycle arrest of human hepatocellular carcinoma Hep3B cells by modulating ERK
phosphorylation. Hispolon inhibited cellular growth of Hep3B cells in a time-dependent
and dose-dependent manner, through the induction of cell cycle arrest at S phase
measured using flow cytometric analysis and apoptotic cell death. Hispolon-induced S-
224
phase arrest was associated with a marked decrease in the protein expression of cyclins
A and E and cyclin-dependent kinase (CDK) 2, with concomitant induction of
p21waf1/Cip1 and p27Kip1. Exposure of Hep3B cells to hispolon resulted in apoptosis as
shown by caspase activation, PARP cleavage, and DNA fragmentation. Hispolon
treatment also activated JNK, p38 MAPK, and ERK expression. Inhibitors of ERK
(PB98095), but not those of JNK (SP600125) and p38 MAPK (SB203580), suppressed
hispolon-induced S-phase arrest and apoptosis in Hep3B cells. These findings establish a
mechanistic link between the MAPK pathway and hispolon-induced cell cycle arrest and
apoptosis in Hep3B cells (Guan-Jhong et al., 2011, Huang et al., 2011). Hispolon has also
been shown to suppress SK-Hep1 human hepatoma cell metastasis by inhibiting matrix
metalloproteinase-2/9 and urokinase-plasminogen activator through the PI3K/Akt and
ERK signaling pathways (Huang et al., 2010b).
Phellinus linteus
Extracts of mycelia derived from Phellinus linteus

have recently been tested as adjuvants for intranasal
influenza vaccine. The adjuvant effects of extracts of
mycelia were examined by intranasal coadministration of the extracts and inactivated A/PR8
(H1N1) influenza virus hemagglutinin (HA) vaccine in
BALB/c mice. The mycelial extract-adjuvanted
vaccines were shown to confer cross-protection
against variant H5N1 influenza viruses (Ichinohe et al., 2010).
Ethanol extracts of Phellinus linteus have been shown to have antioxidant activities
comparable to Vitamin C in scavenging the stable free radical 1,1-diphenyl-2-picrylhyrazyl
(DPPH). The extracts also inhibited lipid peroxidation (LPO) in a concentration-dependent
manner. The study also reported anti-angiogenic activities of Phellinus linteus (Song et al.,
2003).
Phellinus linteus has been reported to sensitise apoptosis induced by doxorubicin (an anticancer drug) in prostate cancer LNCaP cells suggesting that Phellinus linteus may have
therapeutic potential to augment the magnitude of apoptosis induced by anti-prostate
225
cancer drugs (Collins et al., 2006). Phellinus linteus has also been shown to mediate cellcycle arrest at a low concentration and apoptosis in response to a high dose in mouse and
human lung cancer cells (Guo et al., 2007). A Phellinus linteus extract has also recently
been reported to sensitize advanced prostate cancer cells to apoptosis in athymic nude
mice (Tsuji et al., 2010).
Phellinus linteus has been reported to contain constituents that exhibit potent anti-tumour
effects through activation of immune cells. A study in mice has reported that boiling water
soluble fractions from mycelium of P.linteus contain anti-allergic and immuno-potentiating
properties (Inagaki et al., 2005).
An acidic polysaccharide from Phellinus linteus has been shown to markedly inhibit
melanoma cell metastasis in mice, and directly inhibit cancer cell adhesion to, and
invasion through, the extracellular matrix, but that it had no direct effect on cancer cell
growth. In addition, the authors reported that PL increased macrophage NO production.
These results suggest that Phellinus linteus has two anti-metastatic functions - it acts as
an immuno-potentiator and as a direct inhibitor of cancer cell adhesion (Han et al., 2006).
An extract from Phellinus linteus has been shown to have anti-inflammatory activity (Kim
et al., 2004a) via mediation of heme oxygenase-1 in an in vitro inflammation
(macrophage) model (Kim et al., 2006a).
The effect of a mushroom extract of Phellinus linteus on non-cancerous prostate cells
using an experimentally developed rat benign prostatic hyperplasia model has been
studied. The results showed that prostate weight increased significantly by 37% owing to
treatment with the mushroom extract, and in particular, the stromal component of the
prostate increased significantly by 80%. A suppression of transforming growth factorbeta1 expression by 56% was observed with the mushroom extract treatment. It was
found that the mushroom extract enlarged the prostate and therefore administration of
Phellinus linteus extract should be considered carefully by those with an enlarged prostate
(Shibata et al., 2005).
Phellinus linteus has also been shown to suppress growth, angiogenesis and invasive
behaviour of breast cancer cells (Sliva et al., 2008), while hispolon extracted from
Phellinus linteus has been shown to have antiproliferative effects in breast and bladder
cancer cells (Lu et al., 2009).
226
A polysaccharide isolated from Phellinus linteus has also recently been reported to inhibit
the development of autoimmune diabetes in non-obese diabetic (NOD) mice (Kim et al.,
2010c). In this study, 80% of the NOD mice had developed diabetes by 24 weeks of age,
but none of thepolysaccharide- Phellinus linteus -treated NOD mice developed diabetes.
Histological examination of the pancreatic islets revealed that most of the islets isolated
from treated mice were less infiltrated with lymphocytes compared with those of control
mice. The polysaccharide inhibited the expression of inflammatory cytokines, including
IFN-gamma, IL-2, and TNF-alpha by Th1 cells and macrophages, but up-regulated IL-4
expression by Th2 cells in NOD mice. The polysaccharide did not prevent streptozotocininduced diabetic development in ICR mice. These data suggest that this polysaccharide
isolated from Phellinus linteus inhibits the development of autoimmune diabetes by
regulating cytokine expression.
Hispidin from Phellinus linteus exhibited quenching effects against DPPH radicals,
superoxide radicals, and hydrogen peroxide in a dose-dependent manner. Intracellular
reactive oxygen species scavenging activity of hispidin was approximately 55% at a
concentration of 30 M. In addition, hispidin was shown to inhibit hydrogen peroxideinduced apoptosis and increased insulin secretion in hydrogen peroxide-treated
pancreatic beta-cells indicating that hispidin may have anti-diabetogenic properties via
protection of pancreatic beta-cells from reactive oxygen species in diabetes (Jang et al.,
2010a).
A methanol extract of Phellinus linteus has been reported to inhibit the trafficking process
of Newcastle disease virus hemagglutinin-neuramidase, a viral glycoprotein, in virusinfected baby hamster kidney cells. The results suggested that P. linteus extract inhibits
viral glycoprotein expression on cell surfaces through inhibition of trafficking processes
rather than glycoprotein synthesis (Doseung et al., 2011).
Phellinus linteus has been reported to inhibit tumor growth, invasion, and angiogenesis via
the inhibition of Wnt/beta-catenin signaling in SW480 human colon cancer cells (Song et
al., 2011). Extracts from Phellinus linteus have also been shown to induce proapoptotic
effects in the human leukemia cell line K562 (Shnyreva et al., 2010).
In a rat model of permanent focal cerebral ischemia (using Sprague-Dawley rats), a filtrate
of Phellinus linteus broth significant reduced cortical infarct volume 30 and 60 minutes
before onset of cerebral ischemia compared with the control group, while post-treatment
(30minutes after ischemic onset) also significantly reduced cortical infarct volume. A
227
significant benefit of this neuroprotective effect was a wide therapeutic time window since
significant infarct volume reduction was obtained by administration, even after the
ischemic event (Suzuki et al., 2011).
It has recently been demonstrated that polysaccharides from Phellinus linteus (PL) inhibit
proliferation and colony formation of HepG2 and that the growth inhibition of HepG2 cells
was mediated by S-phase cell cycle arrest. Phellinus linteus also markedly inhibited
cancer cell adhesion and invasion of the extracellular matrix and PL-induced apoptosis
was associated with a reduction in B-cell lymphoma 2 levels and an increase in the
release of cytochrome c. The results suggest that PL exerts a direct antitumor effect by
initiating apoptosis and cell cycle blockade in HepG2 cells (Wang et al., 2012a).
The effects of A Phellinus linteus as a complementary therapy in patients with cancer has
been reviewed (Sliva, 2010).
Phellinus rimosus
A polysaccharide protein complex (PPC-Pr) isolated from the mushroom Phellinus
rimosus has been shown to have a protective effect
(at doses of 5 and 10 mg/kg body weight
intraperitoneally for 5 days consecutively) against
oxidative stress induced by gamma radiation (4 Gy)
in Swiss albino mice. PPC-Pr treatment enhanced
the declined levels of antioxidants and demonstrated
a DNA protective effect (as determined by a Comet
assay) as well as significantly increasing the survival rate of animals (Joseph et al., 2012).
An earlier study from the same group at the same doses of PPC-Pr had reported its effect
on alleviating gamma radiation-induced toxicity in the Swiss albino mouse model (Joseph
et al., 2011).
228
Phellinus robustus
It has been reported that melanins from the medicinal
mushroom Phellinus robustus have high antioxidant
and geno-protective properties (Babitskaya et al.,
2007).
Pholiota nameko (Nameko)
A polysaccharide (20, 40, and 60 mg/kg orally)

isolated from Pholiota nameko has recently
been shown to have a hypolipidemic effect
Wistar rats(Li et al., 2010a).
Hypersensitivity pneumonitis to spores of
Pholiota nameko has been reported in a
mushroom farmer, although separation from
the antigen along with corticosteroid therapy,
resulted in the symptoms and inflammatory effects quickly subsiding (Inage et al., 1996).
Pleurotus citrinopileatus
A nonlectin glycoprotein (PCP-3A) isolated from the fruiting
body of the edible golden oyster mushroom Pleurotus
citrinopileatus has been shown to stimulate human
mononuclear cells to secrete cytokines TNF-alpha, IL-2, and
IFN-gamma, which subsequently inhibited the growth of
U937 human myeloid leukemic cells (Chen et al., 2010a).
Anti-inflammatory effects of a bioactive nonlectin glycoprotein (PCP-3A) isolated from the
fresh fruiting body of the golden oyster mushroom, Pleurotus citrinopileatus have been
229
studied in Raw 264.7 cells. The results showed that PCP-3A failed to affect RAW 264.7
viability at a concentration up to 6.25 g/mL, but inhibited lipopolysaccharide (1 g/mL)induced expression, and the production of NO and PGE2 in lipopolysaccharide-activated
macrophages via the down-regulation of certain pro-inflammatory mediators, including
iNOS and NF-kappaB (Chen et al., 2011a).
Pleurotus cornucopiae
Two different ACE inhibitors (oligopeptides) from
Pleurotus cornucopiae have been identified with IC50
values of 0.46 and 1.14 mg/ml. The amino acid
sequences of the two purified oligopeptides were
RLPSEFDLSAFLRA and RLSGQTIEVTSEYLFRH. The
molecular mass of the purified ACE inhibitors was
estimated to be 1622.85 and 2037.26 Da, respectively. Water extracts of the P.
cornucopiae fruiting body also showed a clear antihypertensive effect on spontaneously
hypertensive rats at a dosage of 600 mg/kg (Jang et al., 2011a).
Pleurotus eryngii
The effects of Pleurotus eryngii extracts (PEX) on bone
metabolism have been studied. PEX treatment showed an
increase in the alkaline phosphatase activity of osteoblasts
and in the osteocalcin mRNA expression from primary
osteoblasts. PEX also increased the expression of the Runx2
gene, and the secretion of osteoprotegerin from the
osteoblasts showed marked increases after treatment with
PEX. In vivo studies, using rats with ovariectomy-induced
osteoporosis revealed that PEX alleviated the decrease in the trabecular bone mineral
density (Kim et al., 2006b).
The ergothioneine content of mushrooms has been reported to be in the range of 0.42.0mg/g (dry weight). The white Agaricus bisporus contained the least ergothioneine and
portabellas (brown) contained the highest within the varieties of A. bisporus studied. The
specialty mushrooms tested (Lentinus edodes, Pleurotus ostreatus, P. eryngii, Grifola
frondosa) all contained a statistically significant greater amount of ergothioneine
230
compared to A. bisporus, however, no significant difference was found between the

specialty mushrooms (Dubost et al., 2006).
The antioxidative potency of commercially available mushrooms in Taiwan has been
studied. The order of inhibitory activity of mushroom extracts on oxidation in emulsion
system was Agaricus bisporus > Hypsizigus marmoreus > Volvariella volvacea >
Flammulina velutipes > Pleurotus eryngii > Pleurotus ostreatus > Hericium erinaceus >
Lentinula edodes. In a thermal oxidative stability test, using lard, the order of antioxidative
activity of the mushroom extracts showed similar tendencies, except for the extract of
Lentinula edodes (Fui et al., 2002).
Mycelial extracts (ethyl acetate and 70% ethanol) of 20 higher Basidiomycetes edible or
medicinal mushrooms and culture media extracts (ethyl acetate and Butan-1-ol) have
been evaluated for in vitro anti-inflammatory activity using the cyclooxygenase-1 and -2
enzymes (COX-1 and -2). In general, 70% ethanolic extracts showed lower inhibitory
activity against both enzymes compared to ethyl acetate extracts. Of the mushrooms
tested, the ethyl acetate extracts of Ganoderma applanata, Naematoloma sublateritium,
Pleurotus eryngii, and P. salmoneostramineus showed the highest COX-2 inhibitory
effects compared to COX-1 inhibition. Of the culture media tested in this study, only the
ethyl acetate extracts of the culture medium of Agrocybe cylindracea exhibited high
inhibition of the COX-2 enzyme (Elgorashi et al., 2008). Ceramide from Agrocybe aegerita
has also been reported to inhibit the cyclooxygenase enzymes, COX-1 and -2
(Diyabalanage et al., 2008).
Hypersensitivity pneumonitis induced by Pleurotus eryngii spores has been reported in a
worker in an Eringi (Pleurotus eryngii) mushroom factory who had worked there for 6
years. Chest radiography showed diffuse fine nodular shadows. Chest computed
tomography demonstrated centrilobular nodules and increased attenuation in both lungs.
The patient suffered from hypoxemia while breathing room air. The lymphocyte count in
the bronchoalveolar lavage fluid was increased, and transbronchial lung biopsy
specimens showed lymphocyte alveolitis with epithelioid cell granulomas in the alveolar
spaces. After admission, the patient's symptoms improved rapidly without medication.
However, on his return to work, fever and hypoxemia appeared again. The lymphocyte
stimulating test was positive against extracts of Eringi spores. Precipitins against the
extracts of Eringi spores were detected by the double immunodiffusion test. The diagnosis
was hypersensitivity pneumonitis (HP) caused by Eringi spores. In Japan, more than 30
cases of HP induced by mushroom spores have been reported and therefore this is an
231
occupational health and safety issue, related to air quality in mushroom factories that
needs to be addressed. The symptoms appear to improve without medication (Miyazaki et
al., 2003).
Apoptotic cell death of human leukaemia U937 cells by ubiquinone-9 purified from
Pleurotus eryngii has been reported (Bae et al., 2009). Ubiquinone-9-induced cell death
was characterised with the cleavage of poly (ADP-ribose) polymerase and pro-caspase 3.
A water-soluble polysaccharide extract of Pleurotus eryngii has been shown to
significantly increase the activitiy of antioxidant enzymes and effectively remove free
radicals in a liver-injury mouse model. Furthermore, in a high-fat-load mouse model, the
extract decreased total cholesterol, total triglyceride, and low-density lipoprotein
cholesterol, and increased high-density lipoprotein cholesterol. Histopathological
observations indicated that the extract could effectively prevent excessive lipid formation
in liver tissue (Chen et al., 2012b).
Antioxidant activity, determined by beta-carotene-linoleic acid, reducing power, DPPH,
ferrous-ion chelating abilities, and xanthine oxidase inhibitory activity have been
demonstrated in aqueous-, acetone- and methanol-extracts from the fruiting bodies of
Pleurotus eryngii (Alam et al., 2011a). Pleurotus eryngii and Auricularia auricula-judae
both exhibit a protective effect against H2O2 induced oxidative cell damage with a P.
eryngii methanolic extract also possessing the higher ferrous iron chelating ability (IC50 =
0.42 mg/ml) (Oke and Aslim, 2011).
The anti-allergenic potential of Pleurotus eryngii extract (PEE) in antigen-stimulated RBL2H3 mast cells has been evaluated with PEE inhibiting allergy markers, including release
of hexosaminidase and histamine, in antigen-sensitized RBL-2H3 cells. PEE also
suppressed the expression and production of interleukin-4 and reduced antigen-induced
NFAT and NF-kappaB transcriptional activity in antigen-sensitized mast cells. PEE also
decreased the levels of proinflammatory cytokines and COX-2 and iNOS expression in
antigen-sensitized mast cells, and suppressed antigen-induced signal protein
phosphorylation of Lyn, PLCgamma2, PKC, Akt, and MAP kinases. The data indicate that
this extract from P. eryngii may provide some insights into the mechanisms for the
possible prevention and treatment of allergic and inflammatory responses (Eun Hee et al.,
2011).
232
Intake of Pleurotus eryngii (5% supplementation with a normal diet) has been shown to
decrease plasma glycated haemoglobin and serum glucose levels in a diabetic (db/db)
mouse model. Intake of Pleurotus eryngii also significantly reduced the homeostasis
model measurement of insulin resistance, total cholesterol and triglyceride, and increased
high density lipoprotein (HDL)-cholesterol levels demonstrating hypoglycaemic and
hypolipidemic effects and an improvement in insulin sensitivity in this mouse model
(Jung-In et al., 2010, Kim et al., 2010d). A hypolipidemic effect of Pleurotus eryngii extract
has also been shown in fat-loaded mice and suggested to be due to low absorption of fat
caused by the inhibition of pancreatic lipase (Mizutani et al., 2010).
Pleurotus ferulae
Ethanol and hot water extracts of Pleurotus ferulae
have been shown to have anti-tumourigenic
properties in human cervical cancer and human
lung cancer cell lines. When A549, SiHa and HeLa
cells were incubated with different concentrations
of ethanol and hot water extracts, the ethanol
extracts showed strong cytotoxicity against A549
cells at concentrations over 10 g/mL and against
SiHa and HeLa cells at concentrations over 40 g/mL. The ethanol extracts were the most
prominent anti-tumour agents (of those studied) toward A549 human lung cancer cells
(Choi et al., 2004a).
Pleurotus florida
Anti-tumour potential of the medicinal mushroom
Pleurotus florida against T24 bladder cancer cell
lines has been demonstrated (Selvi et al., 2011).
A study using isolated goat eye lens has reported
that an extract of Pleurotus florida was able to
prevent glucose-induced cataract in this in vitro
model system (Aditya et al., 2011).
233
Pleurotus nebrodensis
Feeding hypercholesterolemic Sprague-Dawley albino
rats a diet containing 5% fruiting bodies of Pleurotus
nebrodensis reduced plasma total cholesterol,
triglyceride, low-density lipoprotein, total lipid,
phospholipids and LDL/HDL ratio by 31.01, 47.71,
62.50, 31.91, 24.65 and 53.06%, respectively, with
significant reductions in body weight. No adverse
effects were reported on plasma albumin, total bilirubin, direct bilirubin, creatinin, blood
urea nitrogen, uric acid, glucose, total protein, calcium, sodium, potassium, chloride,
inorganic phosphate, magnesium, or enzyme profiles. The feeding of these mushrooms
increased total lipid and cholesterol excretion in feces. The data suggest that P.
nebrodensis was acting on the atherogenic lipid profile in these hypercholesterolemic rats
(Alam et al., 2011b). Essentially identical results were also reported for Pleurotus ferulae
in the same animal model (Alam et al., 2011c).
Pleurotus ostreatus (Oyster Mushrooms)

A human intervention study has evaluated the cholesterol
lowering properties of an Oyster mushroom (Pleurotus
ostreatus) diet. Twenty subjects (9 male, 11 female; 20-34
years) were randomized to take either one portion of soup
containing 30 g dried oyster mushrooms or a tomato soup
as a placebo daily for 21 days. The Oyster mushroom soup
decreased triacylglycerol concentrations (0.44 mmol/L) and
oxidized low density lipoprotein levels (7.2 U/mL)
significantly, and showed a significant tendency in lowering
total cholesterol values (0.47 mmol/L; p = 0.059). No
effects on low density lipoprotein and high density lipoprotein levels were observed
(Schneider et al., 2011).
A single-arm, open-label, proof-of-concept study of 8 weeks duration has been completed
which assessed the safety and efficacy of Pleurotus ostreatus (15 g/day orally) in HIVinfected individuals taking antiretroviral therapy that induced hyperlipidemia. Pleurotus
ostreatus at the concentration taken in this study did not lower non-HDL cholesterol in HIV
234
patients with antiretroviral treatment-induced hypercholesterolemia. Small changes in HDL

and triglycerides were not of a clinical magnitude to warrant further study (Abrams et al.,
2011).
Prolonged and exhausting physical activity causes numerous changes in immunity and
sometimes transient increases the risk of upper respiratory tract infections (URTIs). A
double blind, placebo-controlled study has investigated the effect of pleuran, an insoluble
beta-(1,3/1,6) glucan from mushroom Pleurotus ostreatus, on selected cellular immune
responses and incidence of URTI symptoms in athletes. Fifty athletes were randomized to
pleuran or placebo, taking pleuran or placebo supplements during 3 months. Incidence of
URTI symptoms together with characterization of changes in phagocytosis and natural
killer (NK) cell count was monitored.P leuran significantly reduced the incidence of URTI
symptoms and increased the number of circulating NK cells. In addition, the phagocytosis
process remained stable in pleuran group during the study in contrast to placebo group
where significant reduction of phagocytosis was observed. These findings indicate that
pleuran may serve as an effective nutritional supplement for athletes under heavy physical
training. The mechanisms of pleuran function are yet to be determined (Bergendiova et
al., 2011). In a similar double-blind pilot study, 20 elite athletes were randomized to betaglucan (n=9) or placebo ( n=11); these groups consumed 100 mg of beta-glucan
(Imunoglukan) or placebo supplements, respectively, once per day for 2 months. At the
end of the supplementation period, the athletes underwent a 20 min intensive exercise
session. A 28% reduction in natural killer (NK) cell activity below baseline was observed in
the placebo group during the recovery period (1 h after exercise), whereas no significant
reduction in NK cell activity was found in the beta-glucan group, and no significant
decrease in NK cell count was measured in the beta-glucan group during the recovery
period. Immune cell counts did not differ significantly between the groups. These results
indicate that insoluble beta-glucan supplementation from P. ostreatus may play a role in
modulating exercise-induced changes in NK cell activity in intensively training athletes
(Bobovcak et al., 2010).
The effect of Oyster mushrooms on reduction of blood glucose, cholesterol and
triglycerides in diabetic patients has been evaluated in a clinical investigation of 89
subjects. Mushroom consumption significantly reduced systolic and diastolic blood
pressure, lowered plasma glucose, total cholesterol and triglycerides significantly,
whereas there was no significant change in body weight. There were no deleterious
effects on liver or kidney function (Khatun et al., 2007).
235
A hypo-cholesterolemic effect has been shown with Oyster mushrooms (Pleurotus

Ostreatus) in rats with Streptozotocin-induced diabetes. Oyster mushroom (4% dry oyster
mushroom fruit body) lowered cholesterol content by more than 60% in the liver although
it did not significantly affect either the serum triacylglycerol level or the content in liver
(Bobek et al., 1991). Similar results have been observed in rats with a hereditary
hypersensitivity to dietary cholesterol (Bobek et al., 1990). The hypo-cholesterolemic
effects of Oyster mushrooms has been demonstrated to be dose-dependent (Bobek et al.,
1997). A similar hypocholesterolemic effect of the oyster mushroom (Pleurotus ostreatus)
was also observed in hamsters (Bobek et al., 1993b) and in rabbits (Bobek and Galbavy,
1999).
The addition of 4% dried whole oyster mushroom (Pleurotus Ostreatus) to the diet of
Wistar rats has been reported to have led to a reduced level of serum and liver cholesterol
at the end of the 10th week of the experiment. The level of serum triacylglycerols was not
influenced by the mushroom, but was significantly reduced by 13% in liver. The decrease
in serum cholesterol level was a consequence of the decreased cholesterol concentration
in very-low-density lipoproteins (VLDL) and in low-density lipoproteins (LDL). The content
of cholesterol in high-density lipoproteins (HDL) was not influenced by the mushroom.
Dietary Pleurotus ostreatus increased the fractional turnover rate of LDL (by 28%) and
HDL (by 31%) as determined by the analysis of decay curves of 125I-labelled lipoproteins.
The increase in the rate of LDL and HDL catabolism is one of the mechanisms which
mediates the hypocholesterolemic effect of mushrooms in the rat model (Bobek et al.,
1993a).
Feeding of 5% powder of the fruiting bodies of the Oyster mushroom (Pleurotus ostreatus)
to hyper-cholesterolaemic rats reduced their plasma total cholesterol by ~28%, lowdensity lipoprotein-cholesterol by ~55%, triglyceride by ~34%, non-esterified fatty acid by
~30% and total liver cholesterol levels by > 34%, with a concurrent increase in plasma
high-density lipoprotein-cholesterol concentration of > 21%. However, these effects were
not observed in mushroom-fed normocholesterolaemic rats. Mushroom feeding
significantly increased plasma fatty acid unsaturation in both normo- and
hypercholesterolaemic rats, while plasma total antioxidant status was significantly
decreased in mushroom-fed hypercholesterolaemic rats, concomitant with a decrease in
plasma total cholesterol. The study concluded that 5% P. ostreatus supplementation
provides health benefits, at least partially, by acting on the atherogenic lipid profile in the
hyper-cholesterolaemic condition (Hossain et al., 2003).
236
The effects of pleuran, a beta-glucan isolated from Pleurotus ostreatus, have been studied
in a model of acute colitis in rats. Pleuran was given either as a 2% food component or as
a 0.44% pleuran hydrogel drink over 4 weeks. Colitis was induced by intraluminal
instillation of 4% acetic acid and after 48h the extent of colonic damage and several
biochemical parameters were examined. Pleuran supplementation both in food and in
drinking fluid significantly decreased the disposition to colitis. The enhanced activity of
myeloperoxidase in the inflamed colonic segment was reduced by pleuran diets, reflecting
decreased neutrophil infiltration. The mechanism of the described protective effect of
pleuran is not yet clear, but the authors suggest that the pleuran-enhanced antioxidant
defence of the colonic wall against the inflammatory attack maybe a factor (Bobek et al.,
2001).
In vivo injection of three water-soluble proteoglycan fractions from Pleurotus ostreatus
mycelia, which had polysaccharide to protein ratios 14.2, 26.4 and 18.3 respectively, into
Sarcoma-180-bearing mice decreased the number of tumour cells and cell cycle analysis
showed that most of the cells were found to be arrested in pre-G(0)/G(1) phase of the cell
cycle. All of the three proteoglycans elevated mouse natural killer (NK) cell cytotoxicity
and stimulated macrophages to produce nitric oxide. Fourier transform infra red (FTIR)
spectra suggested the presence of a beta-glycosidic bond in all the fractions (Sarangi et
al., 2006).
Anti-proliferative and pro-apoptotic activities of fractions of Pleurotus ostreatus have been
evaluated in HT-29 colon cancer cells in vitro. A hot-water-soluble fraction of the mycelium
of the liquid cultured mushroom was partially isolated and chemically characterized as a
low-molecular-weight alpha-glucan. This low-molecular-weight alpha-glucan possessed
anti-tumourigenic properties, and demonstrated its direct effect on colon cancer cell
proliferation via induction of apoptosis - programmed cell death (Lavi et al., 2006).
Treatment of mice with Pleurotus ostreatus at 100 and 500 mg/kg has suggested that P.
ostreatus may prevent inflammation-associated colon carcinogenesis induced by 2-amino-1methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and promoted by dextran sodium sulfate (DSS),
via combined modulatory mechanisms of inflammation and tumor growth via suppression of
COX-2, F4/80, Ki-67 and cyclin D1 expression in mice. However, incidence of colon tumors
and high grade dysplasia was reduced by 50 and 63% only in the 500 mg/kg dose (Jedinak et
al., 2010). A further study by the same group also showed that the anti-inflammatory activity
of Pleurotus ostreatus is mediated through the inhibition of NF-kappaB and AP-1 signaling
(Jedinak et al., 2011a).
237
A dimeric lectin isolated from fresh fruiting bodies of Pleurotus ostreatus has been shown
to possess potent anti-tumour activity in mice bearing sarcoma S-180 and hepatoma H22. Survival in these mice was prolonged and body weight increase reduced after lectin
treatment (Wang et al., 2000).
Treatment with mushroom Pleurotus ostreatus extract has been suggested to reduce high
blood glucose level, genetic alterations (DNA fragmentation, chromosome aberrations)
and sperm abnormalities in streptozotocin-induced diabetic rats (Ghaly et al., 2011).
An extract of Pleurotus ostreatus (200 mg/kg body weight), has been shown to increase
gene expression of the antioxidant enzyme catalase and reduce the incidence of free
radical-induced protein oxidation during aging in rats, thereby potentially protecting
against the occurrence of age-associated disorders that involve free radicals (Jayakumar
et al., 2010a). A further study by the same group also showed that administration of an
extract of P.ostreatus to aged rats resulted in a significant increase in the levels of
reduced glutathione (GSH) and elevated activities of glutathione S-transferase (GST),
glutathione reductase (GR), and glucose 6-phosphate dehydrogenase (G6PDH) in liver,
kidney, heart, and brain tissues of rats. The results suggest that this extract of P.
ostreatus can prevent the oxidation of GSH and protect its related enzymes during aging
(Jayakumar et al., 2010b). The in-vitro and in-vivo antioxidant effects of the oyster
mushroom Pleurotus ostreatus have recently been reviewed (Jayakumar et al., 2011).
Selenium in selenium-enriched Pleurotus ostreatus has been shown to be highly
bioavailable in a study in Wistar rats (da Silva et al., 2010a).
Pleurotus pulmonarius
Hypoglycaemic activity of an aqueous extract

of Pleurotus pulmonarius in alloxan-induced
diabetic mice has been reported. Pleurotus
pulmonarius extract was administrated orally at
doses of 250, 500, and 1,000mg/kg to separate
groups of mice (normal and alloxan-treated
mice), and serum glucose and body weight
238
were measured. In the separate group of mice, an oral glucose tolerance test was carried
out. Acute oral toxicity data showed no mortality in the normal mice up to 5,000mg/kg,
while oral administration of extracts reduced the serum glucose level in alloxan-treated
diabetic mice at all the doses tested after acute and chronic (28 days) administration. The
extract also showed increased glucose tolerance in both normal and diabetic mice. The
data suggest that the extract possesses hypoglycaemic activity (Badole et al., 2006).
In a subsequent study by the same group, the interaction of an aqueous extract of
Pleurotus pulmonarius with acarbose on serum glucose levels, and on an oral glucosetolerance test in alloxan induced diabetic mice was studied. The anti-hyperglycaemic
effects of aqueous extract and acarbose alone were similar but combination treatment of
the Pleurotus pulmonarius extract with acarbose produced a more synergistic antihyperglycaemic effect than either agent alone (Badole and Bodhankar, 2007).
Orally administered glucans from Pleurotus pulmonarius have also been recently reported
to reduce acute inflammation in dextran sulfate sodium-induced experimental colitis in
mice (Lavi et al., 2010).
Dietary administration of the fruiting body extract or mycelia extract of the edible
mushroom Pleurotus pulmonarius to mice reduced the formation of aberrant crypt foci,
which precedes colorectal cancer, and of microadenomas. The treatments significantly
lowered the expression of proliferating cell nuclear antigen and increased the number of
cells undergoing apoptosis in the colon as well as inhibiting the expression of the
proinflammatory cytokine TNF-alpha in colonic tissue. The extracts inhibited colitisassociated colon carcinogenesis induced in mice through the modulation of cell
proliferation, induction of apoptosis, and inhibition of inflammation (Lavi et al., 2011).
Podaxis pistillaris
Anti-bacterial components of the mushroom Podaxis pistillaris have
recently been reported. Podaxis pistillaris (Podaxales, Podaxaceae,
Basidiomycetes) was found to exhibit anti-bacterial activity against
Staphylococcus aureus, Micrococcus flavus, Bacillus subtilis, Proteus
mirabilis, Serratia marcescens and Escherichia coli. In a culture medium
of P. pistillaris, three epidithiodiketopiperazines were identified by activityguided isolation. Based on spectral data their identity was established as
239
epicorazine A(1), epicorazine B(2) and epicorazine C (3, antibiotic F 3822), which have
not previously been reported as constituents of P. pistillaris (Al-Fatimi et al., 2006).
Schizophyllum Commune (Split Gills Mushroom)

A case of mucoid impaction of the bronchi due to a
hypersensitivity reaction to the monokaryotic mycelium
of Schizophyllum commune has been reported. The
patient was hospitalized because of mild asthma
attacks, persistent cough, peripheral eosinophilia, and
"gloved finger" shadows on a chest roentgenogram.
Cultures of the mucous plugs and sputum samples
yielded white, felt-like mycelial colonies that were later
identified as the monokaryotic mycelium of S. commune
by use of mating tests with established monokaryotic and dikaryotic strains of S.
commune. The results of tests for serum antibody to S. commune cytosol antigen were
positive. Bronchoscopies were effective in removing the mucous plugs and relieving the
patient's symptoms. The authors suggested that the monokaryotic mycelium of S.
commune should be considered as one of the fungi that can cause hypersensitivityrelated lung diseases (Amitani et al., 1996). The incidence of Schizophyllum commune
related effects in patients suffering from diseases of the nasal sinuses also appears to be
on the increase (Buzina et al., 2003).
A lectin from the split gill mushroom Schizophyllum commune has been shown to exhibit
potent mitogenic activity toward mouse splenocytes, anti-proliferative activity toward
tumour cell lines, and inhibitory activity toward HIV-1 reverse transcriptase, but did not
possess any anti-fungal activity (Han et al., 2005).
Aqueous extracts of Schizophyllum commune (27.6%) showed a relatively high
Antioxidant Index (% relative to quercetin) in vitro (Abdullah et al., 2012).
240
Tremella fuciformis (White Wood Ear, White Jelly Leaf)

Tremella fuciformis has been shown to have hypocholesterolemic properties in rats (Cheung, 1996b).
Trametes (=Coriolus) versicolor (Turkey Tail, Yunzhi)
A systematic review of human clinical trials has

concluded that numerous dietary
polysaccharides, particularly glucans, appear to
elicit diverse immunomodulatory effects in animal
tissues, including the blood, GI tract and spleen.
Glucan extracts from the Trametes versicolor
mushroom improved survival and immune
function in human randomised clinical trials of cancer patients. Glucans, arabinogalactans
and fucoidans elicited immunomodulatory effects in controlled studies of healthy adults
and patients with canker sores and seasonal allergies. This systematic review provides a
high level of evidence for these effects (Ramberg et al., 2010)
A polysaccharide isolated from the Trametes (=Coriolus) versicolor (L.: Fr.) Lloyd
(Aphyllophoromycetideae) mushroom has been shown to induce apoptosis in a human
hepatoma cancer (QGY) cell line. The polysaccharide inhibited the proliferation of QGY in
low concentrations (<20 mg/L) and the IC50 value was 4.25 mg/L. Changes that are
characteristic of apoptosis, such as a found trapezoidal belt with DNA, were observed in
the QGY cells treated with the polysaccharide. There was a significant decrease in the
expression of the cell cycle-related genes (p53, Bc1-2, and Fas) in these cells following
treatment with the polysaccharide. The results indicated that the polysaccharide may be a
potential candidate to ameliorate toxic effects when used in cancer therapy (Cai et al.,
2010).
241
Polysaccharide krestin (PSK) is an extract from Trametes versicolor, that has been shown
to be a selective toll-like receptor TLR2 agonist (Lu et al., 2011a), and the activation of
dendritic cells (DC) and T cells by PSK is dependent on TLR2. Oral administration of PSK
in neu transgenic mice significantly inhibited breast cancer growth, with the antitumor
effect of PSK being dependent on both CD8(+) T cell and NK cells, but not CD4(+) T cells.
PSK did not inhibit tumor growth in TLR2(-/-) mice suggesting that the antitumor effect is
mediated by TLR2. The data indicate that PSK is a specific TLR2 agonist and has potent
antitumor effects via stimulation of both innate and adaptive immune pathways (Lu et al.,
2011b). Components of PSK have also been reported to act as ligands for TLR4 receptors
leading to induction of TNF-alpha and IL-6 inflammatory cytokines (Price et al., 2010).
PSK has also been reported to reduce toxicity of current treatments used in patients with
metastatic colorectal cancer (Shibata et al., 2011). The effects of PSK in cancer therapy
and the possible mechanism of action have recently been reviewed (Sun et al., 2012).
Polysaccharide-K (PSK), an extract of the mushroom Trametes versicolor, has been
shown to enhance docetaxel-induced prostate cancer tumor suppression, apoptosis and
antitumor responses in transgenic adenocarcinomas of mouse prostate (TRAMP)-C2bearing mice. Combining PSK with docetaxel significantly induced higher tumor
suppression than either treatment alone, including a reduction in tumor proliferation and
enhanced apoptosis. Combined PSK and docetaxel treatment led to a lower decrease in
number of white blood cells than docetaxel alone, an effect accompanied by increased
numbers of tumor-infiltrating CD4+ and CD8+ T cells. PSK with or without docetaxel
significantly enhanced mRNA expression of IFN-gamma compared to control, but did not
significantly alter T-regulatory FoxP3 mRNA expression in tumors (Wenner et al., 2012).
Yunzhi (Coriolus versicolor) has been reported to modulate various immunological
functions in vitro, in vivo, and in human clinical trials, while Danshen (Salvia miltiorrhiza)
has been shown to benefit the circulatory system by its vasodilating activity. A clinical trial
has been carried out to evaluate the immunomodulatory effects of Yunzhi-Danshen
capsules in post-treatment breast cancer patients. Eighty-two patients with breast cancer
were recruited to take Yunzhi and Danshen capsules with the data showing that the
percentage and the absolute counts of B-lymphocytes were significantly elevated in
patients with breast cancer after taking Yunzhi-Danshen capsules, while plasma sIL-2R
concentration was significantly decreased (Wong et al., 2005). The significance of these
findings is not yet clear.
A polysaccharopeptide from the Turkey Tail fungus Trametes (=Coriolus) versicolor has
242
been reported to be capable of inhibiting human immunodeficiency virus type 1 (HIV-1)

reverse transcriptase and protease, the two enzymes of paramount importance to the life
cycle of the HIV. The polysaccharopeptide inhibited other proteases including trypsin,
chymotrypsin, proteinase K, subtilisin, and elastase to a lesser extent. The anti-HIV
enzyme and immuno-stimulatory activities of the mushroom polysaccharopeptide make it
an interesting potential candidate for the therapeutic treatment of AIDS (Tzi et al., 2006),
although clearly further studies are required to confirm such effects. A recent report has
also suggested that the culture (harvest) duration affects the immunomodulatory and anticancer effects of polysaccharopeptides derived from Coriolus versicolor (Lee et al., 2006).
Coriolus versicolor (CV), also known as Trametes versicolor, has been evaluated for its
cytotoxic activities on a B-cell lymphoma (Raji) and two human promyelocytic leukemia
(HL-60, NB-4) cell lines. The results demonstrated that CV extract at 50 to 800mg/ml
dose-dependently suppressed the proliferation of Raji, NB-4, and HL-60 cells by more
than 90%. The extract however did not exert any significant cytotoxic effect on the normal
liver cell line WRL when compared with a chemotherapeutic anti-cancer drug, mitomycin
C, confirming the tumour-selective cytotoxicity. Nucleosome production in HL-60, NB-4
and Raji cells was significantly increased by 3.6-, 3.6- and 5.6-fold respectively upon the
treatment of CV extract, while no significant nucleosome production was detected in
extract-treated WRL cells. The CV extract was found to selectively and dose-dependently
inhibit the proliferation of lymphoma and leukemic cells possibly via an apoptosisdependent pathway (Lau et al., 2004).
Coriolus versicolor polysaccharide (CVP) extracted from C. versicolor dry fruit bodies by
hot-water extraction and ethanol precipitation has been evaluated against four human liver
cancer (7703, HepG2, 7721, PLC) and four human breast cancer (Bcap37, ZR75-30,
MCF-7, T-47D) cell lines using a cytotoxicity assay. The results showed that the CVP
inhibited the proliferation of 7703, Bcap37, T-47D in low concentration and also inhibited
the proliferation of MCF-7 and ZR75-30, but at high concentrations. The CVP did not
inhibit the proliferation of HepG2, 7721, PLC and human normal liver cell line (WRL). The
CVP was found to selectively inhibit the proliferation of human liver cancer and human
breast cancer (Zhou et al., 2007).
The effect of dietary supplementation with a protein-bound polysaccharide (PSP)containing extract derived from mycelia of Coriolus versicolor on in vitro and in vivo
indices of immune function of young and old C57BL/6NIA mice has been studied. Young
(5 month) and old (23 month) mice were fed purified diets containing 0%, 0.1%, 0.5% or
243
1.0% PSP for 1 month after which time indices of immune function were measured. PSP
supplementation had no significant effect on mitogenic response to concanavalin A (Con
A), phytohemagglutinin (PHA) or lipopolysaccharide (LPS), or on the production of
interleukin (IL)-1, IL-2, IL-4 and prostaglandin E-2 (PGE(2)). Of the in vivo indices of
immune function tested, old mice fed 1.0% PSP had significantly higher delayed-type
hypersensitivity (DTH) response than those fed 0% PSP. No significant effect of PSP was
observed on the DTH response of young mice. The antibody response to sheep red blood
cells was not significantly influenced by PSP in young or old mice, suggesting that the
PSP-containing extract from mycelia of Coriolus versicolor might have a modest immunoenhancing effect in aged mice, but not in young mice (Wu et al., 1998).
Toth et al. have reported the inhibition of intestinal cancer by a hot water extract of the
Coriolus versicolor (Turkey Tail) mushroom in C57bl/6j-Apc(Min) mice (Toth et al., 2007).
A highly N-methylated cyclic heptapeptide, isolated from the mushroom Coriolus
versicolor, has been shown to have an inhibitory effect on fat accumulation by 3T3-L1
murine adipocytes (EC50 = 0.02g/mL) (Shimokawa et al., 2008).
The potential toxicity of Coriolus versicolor standardized water extract after acute and
subchronic administration in rats has been studied. In the acute toxicity study, Coriolus
versicolor water extract was administered by oral gavage to Sprague-Dawley (SD) rats (6
males, 6 females) at single doses of 1250, 2500 and 5000 mg/kg. In the subchronic toxicity
study, the extract was administered orally at doses of 1250, 2500 and 5000 mg/kg/day for 28
days to male and female SD rats respectively. There was no mortality or signs of toxicity in the
acute and subchronic toxicity studies under the above conditions (Hor et al., 2011).
PSP, an active component extracted from Coriolus versicolor has been reported to be
effective in targeting prostate cancer stem/progenitor cells (CSCs). Treatment of the
prostate cancer cell line PC-3 with PSP led to the down-regulation of CSC markers
(CD133 and CD44) in a time and dose-dependent manner. PSP treatment also inhibited
PC-3 cell tumorigenicity in vivo, indicating that PSP can suppress prostate CSC
properties. Transgenic mice (TgMAP) that spontaneously develop prostate tumors, that
were orally fed with PSP for 20 weeks did not develop tomours, while 100% of the mice
that were fed with water only developed prostate tumors at the end of the 20 weeks,
suggesting that PSP treatment can inhibit prostate tumor formation in these mice (Luk et
al., 2011).
244
Volvariella volvacea (Straw Mushroom)

Methanol and water extracts from Volvariella volvacea have
been shown to have antioxidant activity against lipid
peroxidation of rat brain homogenate. The ethyl acetate
sub-fraction of the methanol extract of V. volvacea was
found to have comparable antioxidant activity to caffeic acid
against the oxidation of human low-density lipoprotein
(LDL). The antioxidant activities against lipid peroxidation
were found to correlate with the phenolic content in different
sub-fractions of the mushroom extracts (Cheung and Cheung, 2005).
A report on the fractionation of extracts of the edible mushroom, Volvariella volvacea, has
shown the isolation of two heterocyclic carboxylic acids, namely pyridine-3-carboxylic acid
[nicotinic acid] and pyrazole-3(5)-carboxylic acid and four steroidal metabolites ergosterol,
5-dihydroergosterol, ergosterol peroxide, and cerevisterol. In light of the structural
similarity of pyrazole-3(5)-carboxylic acid to pyrazole-3-carboxylic acids, which act as
agonists for nicotinic acid receptors, the levels of pyridine-3-carboxylic acid and pyrazole3(5)-carboxylic acid were estimated in V. volvacea and two other edible mushrooms,
namely Agaricus bisporus and Calocybe indica. Significant levels of pyridine-3-carboxylic
acid (nicotinic acid) were found in C. indica, and pyrazole-3(5)-carboxylic acid was found
in abundance in A. bisporus. Correlations have been suggested between the occurrence
of these compounds in mushrooms and consumption as well as beneficial health effects
(Mallavadhani et al., 2006).
Volvariella volvacea has been reported to produce a hypotensive response in animals. An
aqueous extract of the mushroom (SME) was prepared and given through intravenous
injections to normotensive rats. An i.v. injection of SME produced a hypotensive effect in
rats with an ED50 of 25mg dry weight/kg body weight. SME did not increase urinary
excretion or sodium diuresis. It produced positive chronotropic and inotropic effects on
isolated right atria and induced contraction of isolated tail artery strips. This latter
contractile response was inhibited by antagonists of serotonin and alpha-adrenoceptor,
ketanserin and phentolamine respectively. Partial purification using dialysis and liquid
chromatography revealed that the hypotensive active substances had molecular weights
between 8,000 and 12,000 daltons. These substances were heat stable and resistant to
trypsin digestion (Chiu et al., 1995). Volvariella volvacea has also been shown to have
hypo-cholesterolemic properties (Cheung, 1996a, Cheung, 1998)
245
Activity against the Gram-positive bacteria Staphylococcus aureus, has been

demonstrated in Volvariella volvacea strain R83, while Volvariella volvacea strain
ATCC62890 showed significantly less antimicrobial activity, but was reported to be a
source of antioxidants (da Silva et al., 2010b).
Wild Edible Fungi

While fungi are a good source of digestible proteins and
fibre, are low in fat and energy and make a useful
contribution to vitamin and mineral intake, nevertheless,
there are some safety concerns with wild fungi. Edible
species might be mistaken for poisonous ones, high heavymetal concentrations (in some regions and countries) in
wild edible fungi (WEF) are a known source of chronic
poisoning and the consumption of WEF can contribute
markedly to the radiocaesium intake of human subjects
(reported for the UK). Some regions of Europe have a
strong WEF tradition, particularly eastern Europe. Only
one-third of adults consume fungi (cultivated species and
WEF) throughout the UK; the average intake of fungi in the UK being estimated to be 0.12
kg fresh weight per capita per year. At least eighty-two species of wild fungi are recorded
as being consumed in the UK, although certain species (e.g. chanterelle (Cantharellus
cibarius), cep (Boletus edulis), Oyster mushroom (Pleurotus ostreatus)) are favoured over
others. Although wild edible fungi are not essential components in the daily diet, they have
been reported to be a nutritionally-valuable addition to the range of vegetables consumed
(de Roman et al., 2006).
In contrast to the above study, a recent analysis of a large variety (7 different families) of
wild edible mushrooms in Greece has shown high mineral contents and low contents of
heavy metals (Pb, Cd and As) suggesting that the mushroom species studied can be
consumed without a risk to health (Ouzouni et al., 2007).
246
25. Conclusions
Although there have been relatively few direct intervention trials of mushroom consumption in
humans, those that have been completed to date indicate that mushrooms and their extracts
are generally well-tolerated with few, if any, side-effects. The most promising data appear to be
those indicating an inverse relationship between mushroom consumption and breast cancer
risk, although the data are generally based on food frequency questionnaires, which can be
affected by recall bias, and therefore these effects need to be confirmed via direct intervention
trials involving mushroom consumption. Although preliminary, new studies reporting protective
effects of mushrooms on beta-amyloid peptide toxicity and mild cognitive impairment (both
precursors to dementia) appear promising and warrant further research. Studies in humans
have shown an increase in the antioxidant capacity in urine and no evidence of liver, renal or
DNA toxicity, and no clinical problems with regard to blood test results, liver and renal function,
glucose and lipid metabolism, or blood pressure. Mushroom components/extracts have been
reported to have stronger health effects/benefits than whole mushrooms in the limited number
of direct human trials to date.
Mushrooms and mushroom components have been reported to have a myriad of positive
health benefits, mainly on the basis of in vitro and in vivo animal trials. However, the majority of
these effects are indirect in that they are due to a stimulation or modulation of natural cellular
immunity. Mushrooms and mushroom components exert many of their positive effects on
health via a balance of T helper cells, the induction of interferon-gamma and certain
interleukins or NO-mediated mechanisms. Many of these immunomodulating effects are due to
the polysaccharide content of mushrooms, either from beta-glucans or from polysaccharide
protein complexes.
247
26. About the authors

Dr Peter Roupas
Dr Roupas obtained his PhD from the Department of Medicine at Monash University,
Melbourne, Australia in 1988 and completed his postdoctoral research at the University of
Michigan Medical School, USA. During his 3 years at the University of Michigan, he was
awarded fellowships from the American Diabetes Association (Michigan) and the Juvenile
Diabetes Foundation International (New York). On his return to Australia, to the
Department of Clinical Biochemistry at the Royal Childrens Hospital, Melbourne, he was
awarded the 1991 Eli Lilly Diabetes Fellowship and a 4-year fellowship from the National
Health and Medical Research Council (NHMRC) of Australia. For the past 16 years, Dr
Roupas has been a Research Team Leader at CSIRO and a Project Leader of projects for
the CSIRO Food Futures Flagship, the Preventative Health Flagship, and the National
Centre of Excellence in Functional Foods relating to the scientific substantiation of health
messages for dietary guidelines and health claims for food standards / regulatory
applications. He is currently the Team Leader of the Knowledge Management team within
the Pre-Clinical and Clinical Health Substantiation group within CSIRO Food and
Nutritional Sciences. Dr Roupas has been an editorial reviewer for 8 scientific journals, an
author of 46 papers in peer-reviewed scientific journals, 30 conference papers and 7 book
chapters. Dr Roupas is also a Scientific Editor for Elsevier Science UK, a member of the
Editorial Board of the Journal of Functional Foods, and a member of the Society of
Editors. Dr Roupas is the Deputy Director of CSIRO Food and Health, and Affiliate Centre
of the Joanna Briggs Institute (JBI), an international collaboration of JBI Centres in 40
countries focussed on evidence-based healthcare and practice. Dr Roupas is also
accredited as a Systematic Scientific Reviewer by the Joanna Briggs Institute.
Associate Professor Manny Noakes
Dr Noakes is currently the Senior Research Dietitian and Research Scientist at CSIRO Food
Sciences and Nutrition where she is the Stream Leader for Diet and Lifestyle Programs. This
stream is a multidisciplinary team aimed at developing substantiated lifestyle intervention
strategies for overweight groups with obesity related morbidities. It relies on the
integration of CSIROs capabilities in nutrition, clinical science, physical activity,
behavioural science and nutritional genomics. Dr Noakes has managed clinical nutritional
trials for the CSIRO Clinical Research Unit since 1990 and has been involved in the
conduct of many published clinical studies to establish the health potential of diets, food
products, nutrients, supplements and pharmaceuticals. Further to this, CSIRO capabilities
248
in analytical techniques related to food composition and the limitation of food composition
databases is critical in understanding the usefulness and limitations of nutrient intake
assessment. These skills are highly relevant to the assessment and interpretation of
nutrient composition derived from dietary studies.
Dr Noakes was actively involved in the research, development and communication of the
CSIRO Total Wellbeing Diet Books 1 and 2 which are aimed at minimising health risks
through better nutrition and weight management. The books have collectively sold over 1
million copies in Australia as well as gaining international recognition with translations into
13 languages. The books success has sparked considerable community activity in
healthy lifestyle behaviours. In recognition of both the commercial success and the
science which underpins the CSIRO Total Wellbeing Diet, Dr Noakes was awarded 2
CSIRO medals for both Business Excellence and Research Excellence in 2005. In
addition, she was awarded an Outstanding Achievement Alumni Award by Flinders
University, Australia in 2006 in recognition of her achievements in nutritional science. Dr
Noakes is a former Chair of the Heart Foundation's Nutrition and Metabolism Advisory
Committee, Australia and has been involved in the development and oversight of several
comprehensive evidence-based position papers on key nutrition issues that relate to diet
and cardiovascular disease. She is also on the advisory panel for the Food Information
Program Criteria Working Group which has provided an excellent framework for
developing nutrition benchmarks for food categories based on knowledge of current
population intakes of these foods, food composition profiles and technological barriers to
changing nutrient profiles. Dr Noakes is the author of over 100 scientific papers, including
several scientific book chapters, and contributes to peer review of papers for many
nutrition journals. Dr Noakes is the Director of CSIRO Food and Health, and Affiliate
Centre of the Joanna Briggs Institute (JBI), an international collaboration of JBI Centres in
40 countries focussed on evidence-based healthcare and practice. Dr Noakes is also
accredited as a Systematic Scientific Reviewer by the Joanna Briggs Institute.
Christine Margetts
Ms Margetts has qualifications in librarianship, information management, and writing and
editing. She has over 25 years experience in providing information services to scientists
and researchers working in agriculture, engineering and food sciences. As part of the
Knowledge Management team within CSIRO Food and Nutritional Sciences, Ms Margetts
provides intensive information services in food and ingredient innovations to scientific
groups. This includes developing in-depth literature searches and reviews, assistance with
scoping studies and project reports and alerting researchers and business staff
249
on scientific, marketing and intellectual property developments in the food industry. Ms

Margetts is also accredited as a Systematic Scientific Reviewer by the Joanna Briggs
Institute (JBI), an international collaboration of JBI Centres in 40 countries focussed on
evidence-based healthcare and practice.
Debra Krause
Ms Krause has a Bachelor of Science degree from Deakin University, Melbourne with
over 26 years experience in food research organisations. This includes 10 years dairy and
meat research and extension experience, 3 years business development experience, 10
years experience in confectionery research and applications, including 5 years concurrent
experience in milkfat research and extension activities. Ms Krause has held Secretariat
roles for Dairy Australia's Ingredients by Design program and for CSIROs Innovative
Foods Centre (IFC) 'Advanced processing and innovative foods program', where she has
organised and participated in industry days and conferences, prepared fact sheets,
industry awareness articles, annual and final reports, liaised with stakeholders from
government, universities, research directors, researchers and companies to deliver
outcomes of the $9.8M IFC program. Ms Krause is currently part of the CSIRO Food and
Nutritional Sciences (CFNS) Knowledge Management team, undertaking scientific
literature searches and reviews for a range of projects and project proposals including the
development of the Healthy Brain Book proposal as part of CSIROs Preventive Health
Flagship. Ms Krause is also accredited as a Systematic Scientific Reviewer by the Joanna
Briggs Institute (JBI), an international collaboration of JBI Centres in 40 countries
focussed on evidence-based healthcare and practice.
Pennie Taylor
Ms Taylor is an Accredited Practising Dietitian and the Senior Research Dietitian for the
Clinical Research Unit at CSIRO Food and Nutritional Sciences. Ms Taylor has worked in
the health and fitness industry for over 10 years and also works part-time in her own
private practice, specialising in weight management, weight-loss surgery and diabetes
care. Her role at CSIRO is to provide dietetic expertise to senior scientists to develop and
deliver designer diets for clinical trials, analyse dietary data and assist in preparing
scientific and commercial publications. She has a strong interest in dietary patterns
associated with weight-loss surgery and the impact of surgery on dietary tolerance and
long-term weight loss. Ms Taylor is also accredited as a Systematic Scientific Reviewer by
the Joanna Briggs Institute (JBI), an international collaboration of JBI Centres in 40
countries focussed on evidence-based healthcare and practice.
250
Anti- Cancer
(Cervical, Ovarian,
Endometrial)
Unspecified extract
Lingzi
Lentinan
Clitocinet
Anti-cancer (Gastric) Polysaccharide K
Lentinan (in adjunct with
immuno-chemotherapy)
Anti-cancer
Ethanol extract of whole
(Prostate)
mushroom
Anti-Cancer
(Pancreatic
advanced solid
malignancy)
Immuno-
modulation:
(Post-menopausal
Breast Cancer)
Immuno-
Agaricus blazei Murill Kyowa

(AbMK)
Ganoderma lucidium
Lentinus edodes
Leucopaxillus giganteus
Lentinus edodes
Ganoderma lucidum
extract
Ganoderma lucidum
Extract
Agaricus bisporus
Irofulven (cytotoxin)
Omphalotus olearius
Note: Not an edible mushroom
Grifola frondosa
Andosan
Agaricus blazei Murill (AbM)
30
colonic cancer cells via up-regulation of expression

of pro-apoptotic proteins and down-regulation of
anti-apoptotic proteins
Increase activity of natural killer cells
Ahn et al 2004
Improve chemotherapy side effects (e.g. appetite,
alopecia, emotional stability & general weakness)
(in vivo undergoing chemotherapy)
Anti-proliferative effects via induction of apoptosis Chen et al 2010;
Liu et al 2009;
Ren et al 2008
Prolong survival; more effective in patients with
Oba et al 2009
lymph-node metastasis vs. non- node metastasis
( in vivo)
Dose extract 6mg per day improve the total
Noguchi et al 2008a, b
International Prostate Symptom Score (IPSS) of
men with lower urinary tract symptoms via strong
5-alphal-reductase inhibitory activity (in vivo)
Inhibit proliferation and induce apoptosis in PC-3
Jiang et al 2004b;
human prostate cancer cells. Inhibition of prostate Stanley et al 2005
cancer-dependent angiogenesis is suggested to be
due to modulation of MAPK and Akt signalling
Effect of 4-14g of extract for a year in patients
NCT00779168
with biochemically recurrent prostate cancer and Ongoing study
and toxicity of prolonged use. (clinical trial first
registered 2008)
Daily dose of 10.64mg/m2 as a 5 minute i.v.
Eckhardt et al 2000
infusion for 5 days every 4 weeks resulted in anti-
tumor activity; and intermittent dosing schedules
had positive pre-clinical anti-tumor effects (in vivo)
Immunologically stimulatory and inhibitory
Deng et al 2009
measurable effects in peripheral blood of patients
free of disease after 1st treatment (in vivo)
Stimulation of whole blood ex vivo with 0.5-5.0%
Johnson et al 2009
modulation
(Healthy Volunteers)
(Himematsutake) 82%
Hericiums erinaceum
(Yamabushitake) 14.7%
Grifolia frondosa 2.9%
Immuno-modulation Alpha-glucans
(Mild
hypercholesterolae
mia)
Agaricus bisporus
Immuno-modulation Glucan
(Cancer)
Immuno-modulation Various mushroom
(variety of disease
bioactive(s)/ extract(s)
states)
Trametes versicolor
Diabetes (Type II)
AbM extract (in

combination with
metformain and
gliclazide)
extract
Agaricus blazei Murill (AbM)
Protein-bound
polysaccharides (A-PBP
and L-PBP)
extract
Agaricus blazei
Lentinus edodes
Cardiovascular
Disease
(Biomarkers)
Brain Health &

Cognition
of extract containing AbM produced a dose-

dependent increase in all cytokines studied from 2
to 399-fold (TNF-alpha). In vivo there was a
significant reduction in levels of IL-1-beta (97%),
TNF- alpha (84%), IL-17 (50%) and IL-2 (46%).
Discrepancy in results associated with antioxidant
activity of AbM in vivo and limited absorption of
its large beta-glucans across the intestinal mucosa
to the reticuloendothelial system and blood.
Consumption of fruit juice enriched with 5g
Volman et al 2010a
glucans/ day lowered lipopolysaccharide-induced
TNF alpha production by 69%. No effects on IL-
1beta and IL-6 and decreased production of IL-12
and IL-10 was observed (in vivo). Contrarily alpha
glucans has been observed to stimulate immune
response in an in vitro mouse model.
Improved survival and immune function (in vivo)
Ramberg et al 2010
Multiple variety
Pleurotus ostreatus (Oyster

Mushroom)
Hericium erinaceus
(Yamabushitake)
31
Effects on natural killer cells, macrophages, T cells

and their cytokine production; and via the
activation of Mitogen Activated Protein Kinase
(MAPK) pathways
Improve insulin resistance potentially by the
mechanism that caused an increase in adiponectin
concentration after taking the extract for 12
weeks (in vivo)
Significant reduction in systolic and diastolic blood
pressure, blood glucose, total cholesterol and
triglycerides (in vivo)
Weight-controlling and hypolipidemic effect via a
mechanism involving absorption of cholesterol (in
vivo)
Increase in scores on cognitive function scales in
men and women diagnosed with mild cognitive
Kim et al 2007
Hsu et al 2007
Khatun et al 2007
Kweon et al 2002
Mori et al 2009
Hepatitis B
Anti-viral (HIV)
Anti-viral
(Poliomyelitis)
Asthma
Dilinoleoyl-
phosphatidylethanolamin
e (DLPE)
Hericium erinacium
Hericenones C to H;
Erinacines A to I
Hericium erinacium
impairment (in vivo)

Protect against neuronal cell death caused by
beta-amyloid peptide (A beta) toxicity,
endoplasmic reticulum (ER) stress and oxidative
stress
Improves the Functional Independence Measure
(FIM) score or retard disease progression in
patients with dementia (in vivo)
Induce synthesis of nerve growth factor (NGF) (in
vitro and in vivo)
Agarius blazei Murill (AbM)
Ganopoly
Ganoderma lucidum
1. Farnesyl
Ganoderma colossum
hydroquinone,
ganomycin I
2. Ganomycin B
Polysaccharides
Unspecified bioactive
extract
Agarius brasiliensis (previously

Agarius blazei ss Heinem)
Cordyceps (unspecified variety)
32
Decrease levels aspartate aminotransferase and

alanine aminotransferase, hence normalising liver
function of patients with Hepatitis B (in vivo).
To be noted: results based on a sample of 4
patients thus larger and controlled studies are
required to confirm the effects.
Hypoglycaemic activity, anti-viral and liver
protective effects in chronic hepatitis B (in vivo).
To be noted: authors indicated despite
pharmacological activities, clinical proof is lacking.
Competitive inhibition of the HIV-1 protease
enzyme by ganomycin B and docking with the HIV-
1 protease crystal structure by both compounds
Kawagishi and Zhuang

2008
Kawagishi and Zhuang

2008
Hsu et al 2008a
Zhou et al 2005
El Dine et al 2009
Anti-viral activity when added during poliovirus

Faccin et al 2007
infection: potentially acting at the initial stage of
viral replication
Inhibit proliferation and differentiation of Th2 cells Sun et al 2010
& reduce the expression of cytokines by down-
regulating the expression of GATA-3 mRNA and
up-regulating the expression of Foxp3 mRNA in
peripheral blood mononuclear cells. Alleviate
chronic allergic inflammation by increasing the
Constipation
Fiber
Auricularia (Ear mushrooms)
Osteoporosis
Polycan, purified -
glucan extract
Aureobasidium pullulans
Nutritional status of
Hepatitis C patients
Dehydrated powder
Agaricus Blazei (Murrill) ss.

Heinemann (Sun mushroom)
Weight loss and

control
Mushrooms
Not stated
Weight loss
Mushrooms
Agaricus bisporus
Antihperlipidaemia
(HIV patients)
Oyster mushroom
powder
Pleurotus ostreatus
Glaucoma
Aqueous extract
Pleurotus tuberregium
Immune function
Not stated
Not stated
Immune function
(enhancement of
hematopoiesis in
myelodysplasia)
Extract
Grifola Frondosa (Maitake)
33
level of interleukin-10 (in vivo)

Fiber supplements using ear mushrooms improve
constipation related symptoms without serious
side effects (in vivo)
Kim et al 2004
Effect of 150mg/day for 12 weeks of Polycan on

biochemical markers of bone metabolism (clinical
trial first registered 2011))
Effect on nutritional status and liver function of
10g/day for 5 months on hepatitis C patients
(clinical trial first registered 2007)
Substituting mushrooms for meat to control body
weight in a caloric restricted diet to result in a
20lb weight loss over 6 months(clinical trial first
registered 2008)
Dietary compensation for potential calorie and fat
savings by substitution of white button
mushrooms for meat products over 4 days (clinical
trial first registered 2008)
No effect on lowering of lipid levels in HIV patients
receiving Antiretroviral treatment (ART) regimens
which commonly cause significant lipid elevations,
Effect of 1-4g/100mL treatment dose on
intraocular pressure of the eye (clinical trial first
registered 2009)
Effect of consumption of 3oz or 6oz of mushrooms
per day in the form of a dietary supplement is
effective in enhancing the function of T cells.
(clinical trial first registered 2011)
NCT01402115
Completed*
Effect of 3mg/kg body weight of extract given 2

times /day for 3months to patients with
myelodysplasia to determine any improvement in
their neutrophil count and function. Laboratory
studies have shown that Maitake can reduce the
NCT01099917
Recruiting
NCT00564811
Completed*
NCT01177085
Completed*
NCT00198770
Completed*
Abrams et al 2011
NCT01017068
Status unknown
NCT01398176
Ongoing
growth of cancer in animals through enhancement

of immune function. (clinical trial first registered
2010)
Inflammatory bowel
disease
(anti-inflammatory)
Andosan
Inflammatory bowel Andosan

disease
(antit-inflammatory)
Immuno-modulation Extract
(Multiple myeloma)
Effect of daily oral ingestion of 30mL x2 for 21

NCT01496053
days AndoSanTM in patients with ulcerative colitis Recruiting
(UC) and Crohn`s disease (CD), to experience
clinical, biochemical and genetical improvement in
their disease. (clinical trial first registered 2011)
Agaricus blazei Murill
After 12 days' ingestion of AndoSan, baseline

Forland et al 2011
plasma cytokine levels in ulcerative colitis was
reduced for MCP-1 (40%) and in LPS-stimulated
blood for MIP-1beta (78%), IL-6 (44%), IL-1beta
(41%), IL-8 (30%), G-CSF (29%), MCP-1 (18%) and
GM-CSF (17%). There were corresponding
reductions in Crohns disease: IL-2 (100%), IL-17
(55%) and IL-8 (29%) and for IL-1beta (35%), MIP-
1beta (30%), MCP-1 (22%), IL-8 (18%), IL-17 (17%)
and G-CSF (14%), respectively. Baseline
concentrations for the 17 cytokines in the UC and
CD patient groups were largely similar. Faecal
calprotectin was reduced in the UC group.
Ingestion of an AbM-based medicinal mushroom
by patients with IBD resulted in interesting anti-
inflammatory effects as demonstrated by declined
levels of pathogenic cytokines in blood and
calprotectin in faeces.
Effect of 60mL extract daily as a supplementary

NCT00970021
treatment in addition to chemotherapy in patients Recruiting
with multiple myeloma. (clinical trial first
registered 2011)

*No results reported as of 15 June 2012
34
Table 8: Properties and mechanisms of bioactive compounds and mushroom extracts evaluated in animal models or animal cell lines
EFFECT/ DISEASE
BIOACTIVE or EXTRACT
MUSHROOM VARIETY
MECHANISM
REFERENCE
STATE
(in vitro/ in vivo)
Maitake
M
ushroom
D

Grifola
f
rondosa

Reduce
g
rowth
i
n
T24 bladder cancer cells
Anticancer (-
Louie et al 2010
Fraction (in combination
potentially by triggering double-stranded DNA-
(Bladder)
with interferon-alpha 2b)
dependent protein kinase activation that may act
on the cell cycle to cease cancer cell growth (in
vitro)
Inhibit growth during cell-cycle progression of 5637
and T-24 bladder cancer cells largely due to G2/M-
phase arrest (in vitro)
Inhibit proliferation of leukemic tumor cell lines
(e.g. U937, MOLT4,HL60, K562)
Inhibit proliferation of HL-60 leukemia cells & other
leukemia human cell lines via induction of
apoptosis.
Exhibit tumor-selective cytotoxicity with no
significant cytotoxic effects on normal cell lines (in
vitro)
Cordycepin (3-
deoxyadenosine)
Cordyceps militaris
Anti-cancer
(Leukemia)
Agaritine
Various unspecified
bioactives/ extracts
Agaricus bisporus; Agaricus

blazei; Hypsizigus marmoreus;
other unspecified varieties

Anti-cancer (Liver)
1.
2.
Triterpenoids
Hyper-branched
beta-glucan
3.
Unspecified
bioactive/ extract(s)
extract(s)
Ganoderma lucidum
Pleurotus tuberregium
Cordyceps sinensis and
Inonotus obliquus
Inhibit proliferation of HepG2 human

hepatocellular carcinomas
Exhibit tumor-selective cytotoxicity (in vitro)
Agaricus blazei
Pleurotus pulmonarius
Hepato-protective effects on both chemically-

induced liver toxicity and hepato-carcinogenesis in
rodents (in vivo)
Aqueous extract
Hypsizigus marmoreus
Intraperitoneal administration exhibit inhibitory

activity against spontaneous tumor metastasis and
decreases number of metastasised nodules in mice
with Lewis lung carcinoma (in vivo)
Anti-cancer (Lung)
Lee et al 2009c
Endo et al 2010
Gao et al 2007; Jin et al
2007; Bae et al 2009;
Mizumoto et al 2008;
Hsu et al 2008b;
Calvino et al 2010; Lau
et al 2004
Weng et al 2007; Tao
et al 2006; Wu et al
2007; Youn et al 2008;
Lin et al 2003
Barbisan et al 2002;
Pinheiro et al 2003;
Wasonga et al 2008
Saitoh et al 1997
Lucialdehydes A-C
Ganoderma lucidum
extract(s)
Phellinus linteus
Anti-cancer (Lung & Blazein

stomach)
Anti-cancer ( Lung
and cervical
Anti cancer (Skin)
DNA damage


(Himematsutake)
extract(s)
Pleurotus ferulae
extract(s)
Methanol extract
Lentinula edodes
Proflamin
Flammulina velutipes
Acidic polysaccharide
Phellinius linteus
Unspecified aqueous
bioactive/ extract(s)
Heat- labile protein
Agaricus bisporus
1. Cold (20) water

extracts
2. Hot (100) water
Agaricus bisporus
Ganoderma lucidum
Coriolus versicolour
36
Cytotoxic against murine and human tumor cells

(Lewis lung carcinoma, T-47D, Sarcoma 180, Meth-
A tumor cell lines) (in vivo)
Mediate cell-cycle arrest at a low concentration and
apoptosis in response to a high dose in mouse and
human lung cancer cell (in vivo and in vitro)
Induce cell death and morphological change
indicative of apoptopic chromatin condensation in
human lung cancer LU99 and stomach cancer
KATOIII cells
Exhibit cytotoxic effects on human lung and cancer
cell lines (A549, SiHa and HeLa cells) ( in vitro)
Gao et al 2002

Reduce cell proliferation and induce apoptosis in

CH72 mouse skin carcinoma cells (in vivo)
Reduce B-16 melanoma cell viability and the
proliferation of tumor cells (arrest in the G-/G1
phase of the cell cycle) followed by apoptotic and
secondary necrotic cell death (in vitro)
Increase median survival time of mice treated with
B-16 and Ca-744 (in vivo)
Inhibit melanoma cell metastasis in mice
Directly inhibit cancer cell adhesion to and invasion
through the extracellular matrix
Increase macrophage NO production (in vivo)
Reduce DNA damage in liver (induced by
diethylnitrosamine (DEN) in adult male Wistar rats)
(in vivo)
Protect Raji cells (human lymphoma cell line)
against H2O2O-induced oxidative damage to cellular
DNA (in vitro)
Protective against H2O2O-induced oxidative damage
to cellular DNA (in vitro)
Gu & Belury 2005
Guo et al 2007

Itoh et al 2008
Choi et al 2004
Harhaji et al 2008
Ikekawa et al 1985
Han et al 2006
Barbisan et al 2003
Shi et al 2002
Rocha et al 2002
extracts
extract(s)
Inonotus obliquus
Reduce DNA fragmentation
Aqueous extract
Agrocybe cylindracea (strain B)
Beta-glucan
Agaricus brasiliensis
Beta-glucan
Agaricus blazei
3. Water-soluble
Ganoderma lucidum
Protects DNA against OH-mediated strand breaks

damage in HepG2 cells
In the dose range 20-80 g/ml exhibited significant
dose-dependent protective effect against damage
induced by hydrogen peroxide and Trp-P-2
Protective against DNA damage caused by
benzo[a]pyrene possibly mediated via binding to
benzo[a]pyrene or the capture of free radicals
produced during its activation
Protective against hydroxyl radical-induced DNA
strand breaks
polysaccharide;
4. Hot water extract
Aqueous extract
Protein extract
Ganoderma lucidum
Ganoderma lucidum (Selenium-

enriched )
Anti- Arthritic
Beta-(1,3/1,6)-D-glucan
Pleurotus ostreatus
Bone Health
Ethanol extracts
Vitamin D2 and/or
calcium
Ganoderma lucidum
Lentinula edodes
(UV irradiated)

Aqueous extract
Grifola frondosa
37
Protection of radiation-induced plasmid pBR322

DNA strand breaks and inhibition of lipid
peroxidation
Strong protective effects against oxidative damage
possibly associated with Ses role in increasing
antioxidant activities of protein extracts
Protection of DNA from hydroxyl radical oxidative
damage
Immuno-modulating effect on all cytokine plasma
levels measured (in vivo)
Improve bone density in rats
May improve bone mineralisation through a direct
effect on the bone and by inducing the expression
of calcium absorbing genes in the duodenum and
kidney (in vivo)
Increase alkaline phosphatase activity of
osteoblasts
Increase mineralisation hence acting as a bone-
Park et al 2004

Wang et al 2004
Angeli et al 2006
Angeli et al 2009
Kim & Kim 1999

Pillai et al 2006
Zhao et al 2004

Zhao et al 2008
Bauerova et al 2009
Miyamoto et al 2009
Lee et al 2009a
Saif et al 2007
inducing agent
Alleviate the decrease in trabecular bone mineral
density in ovariectomy-induced osteporosis in rats
(in vivo)
Protect against bone loss caused by oestrogen
deficiency
Dose-dependent inhibition of proliferation and
lattice contraction in an in vitro model of wound
healing (human ocular firoblasts in monolayers and
in 3-D collagen lattices)
Accelerate wound healing in diabetes mellitus via
an increase in the migration of macrophages and
fibroblasts, and beta-glucan from SC directly
increasing the synthesis of type I collagen (in vivo)
Active component with healing efficacy on acetic
acid-induced ulcers in rats (in vivo)
Reduce ulceration when used in pre-treatment in
ethanol-induced gastric ulcers in rats (in vivo)
Increase activities of serum antioxidant enzymes
and decrease levels of serum mucosal interleukin-2
(IL-2) and TNF--a in rats with oral ulceration (in
vivo)
In vitro: incubation of extract with selenite-
challenged lenses result in a decrease in lens
opacification by maintaining antioxidant
components at near normal levels
In vivo: extract prevents cataracts in 75% of rats
Pleurotus eryngii extracts Pleurotus eryngii

(PEX)
Wound Healing
Eye Health
Ethanol extract
Pleurotus eryngii
extract(s)
Agaricus bisporus
Includes beta-glucan
Sparassis crispa (SC)
Polysaccharide fractions
Ganoderma lucidum
extract(s)
Polysaccharide
Hericium erinaceus
extract(s)
Pleurotus ostreatus
Lentinus edodes
38
Kim et al 2006
Shimizu et al 2006
Batterbury et al 2002
Kwon et al 2009
Gao et al 2004
Mahmood et al 2008
Yu et al 2009b
Isai et al 2009

Mushrooms and Health Report 2012

Uploaded by

Document Information

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Mushrooms and Health Report 2012

Uploaded by

Copyright:

Available Formats

Mushrooms

Report prepared for:

5. EFFECTS OF MUSHROOMS AND MUSHROOM COMPONENTS ON HEALTH .................................. 28

10.1 BLADDER CANCER........................................................................................................................................... 82

17. EFFECTS ON OSTEOPOROSIS / BONE MINERAL DENSITY .............................................................. 135

Nutritional Profiling: The current review of nutritional data identified an additional 31

In comparison to common vegetables, the common white button mushroom (Agaricus

Cultivated mushrooms (e.g. Agaricus bisporus/white, Agaricus bisporus/brown, Lentinus

by mushroom extracts. A decrease in aromatase activity has recently been demonstrated in

Anti-Diabetogenic Effects: The consistency between the effects of mushroom extracts in

Anti-Microbial Properties: Initial studies in humans have suggested anti-microbial

Anti-Oxidant Activity: A recent (2012) comparison of the antioxidant properties and

Cardiovascular Health: A reduction in total cholesterol following mushroom consumption

Immune Function: A recent systematic review of immunomodulatory dietary

activation of Mitogen Activated Protein Kinase (MAPK) pathways.

Cognition / Brain Health: Although preliminary, data showing protective effects of

Hypersensitivity to Mushrooms: Spores of mushrooms are airborne components and can

Bio-accumulation: Mushrooms can bioaccumulate undesirable levels of compounds such

Food Safety Studies / Agaritine: A number of safety assessments on consumption of

Medline on Pub Med

Science Citation Index (searched on CSIRO Network)

Cochrane Central (Database of Systematic Reviews and Cochrane Collaboration

Centre for Reviews and Dissemination Databases (Database of Reviews of Effects

Joanna Briggs Institute (JBI) Library of Systematic Reviews.

ISRCTN International metaRegister of Current Controlled Trials which includes the

Action Medical Research (UK)

Medical Research Council (UK)

The Wellcome Trust (UK)

NIHR Health Technology Assessment Program (HTA) (UK)

NIH Clinical Trials.gov Register

Cochrane Collaboration Central Register of Controlled Trials

Australian and New Zealand Clinical Trials Registry (ANZCTR)

Australian New Zealand Clinical Trials Registry

Chinese Clinical Trial Registry

Clinical Trials Registry - India

German Clinical Trials Register

Iranian Registry of Clinical Trials

Japan Primary Registries Network

Sri Lanka Clinical Trials Register

The Netherlands National Trial Register

4. Nutrient Profiling of Mushrooms

Table 1: Mushroom varieties added to 2012 Report

Common Mushroom (Agaricus Bisphorus)

Common Mushroom (Agaricus Bisphorus)

Mushroom Portabella (Portobello), raw (Can)

Mushrooms, white microwaved (Can)

Mushroom Brown Italian (Crimini) raw (Can)

Boletus edible (Fin)

Matsutake, canned in brine solids (Jap)

Mushroom Boletus, Russula (Fin)

Mushroom fried Agaricus bisporus (Fin)

Boletus edible, boiled (Fin)

False Morel (Fin)

Mushroom, boiled, drained with salt (Can)

Milk-cap Northern (Fin)

Mushroom, straw, canned, drained solids (Can)

Yanagimatsutake, raw (Jap)

Mushroom Portabella (Portabello), grilled (Can)

Shimeji Honshimeji, raw (Jap)

Mushroom, straw, canned, drained solids (USDA)

Culinary Specialty Mushrooms

Numeisugitake, raw (Jap)

Culinary Specialty Mushrooms

Tamogitake, raw (Jap)