C H A P T E R

50
Chinese Ginseng
Mildred S. Yang and Mei Yi Wu

INTRODUCTION have the highest medicinal value (Gui and Ryu, 2014;
Liu and Xiao, 1992). The content of ginsenosides differs
Chinese ginseng refers to the root of a perennial plant, in the different species of ginseng as well as in the dif-
Panax ginseng, which grows in the mountains of north- ferent parts of the plant. Thirty-eight ginsenosides have
ern China, Eastern Siberia, Japan, and Korea (Gillis, been identified in P. ginseng (Choi, 2008).
1997; Park etal., 2005). It is a slow-growing plant with Ginsenosides are saponines that are derivatives of
one leaf that grows in the first year, and then one leaflet triterpene dammarane. Each ginsenoside is character-
appears in each subsequent year until the sixth year. ized by the position of its sugar moiety on the dam-
The root of the plant has two to five ramified rootlets marane and triterpene rings and can be divided into
that also increase in size as the plant matures (Figure three categories: oleanolic, panaxadiol, and panaxatriol
50.1). The thickness of the rhizome has been considered (Liu and Xiao, 1992). The most abundant saponins are
an important indicator of the quality and value of the protopanaxadiol (PPD; e.g., Ra, Rb, Rc, Rd, Rg3, Rh2)
ginseng (WHO, 1999).
Eleven ginseng species of the genus Panax have been
identified (Table 50.1). The Asian ginseng includes Panax
notoginseng, Panax japonicas, and P. ginseng, whereas North
American ginseng belongs to the genus Panax quinque-
folium. Panax notoginseng is commonly found in China,
whereas P. ginseng is grown in areas around the board-
ers between China and Korea (Park et al., 2012; Shim
etal., 2005). Current literature often regards P. ginseng to
be the Chinese ginseng, or renshen (Natural Medicines
Comprehensive Database, 2014; Gardner and McGuffin,
2013).The genus Panax contains the active ingredient
ginsenoside. Other genus, such as the Siberian ginseng
(Eleutherococcus senticosus), are not considered as ginseng
because they do not contain this active ingredient (Yun,
2001). In the following discussion, ginseng refers mainly
to the P. ginseng unless otherwise indicated.

THE CHEMICAL CONTENTS

OF GINSENG

Ginseng contains many valuable substances. Besides

proteins and carbohydrates, ginseng also contains vola-
tile oils, ginsenosides (ginseng saponins), amino acids, FIGURE 50.1 Illustration of ginseng from the Compendium of
vitamins, and fatty acids. Among these, ginsenosides Materia Medica (Ben Cao Gang Mu).

Nutraceuticals.
DOI: http://dx.doi.org/10.1016/B978-0-12-802147-7.00050-4 693 2012
2016 Elsevier Inc. All rights reserved.
694 50. Chinese Ginseng

TABLE 50.1 Classification of Species in Genus Panax

Genus Sections Series Species Common names

Panax Panax Panax P. bipinnatifidus, Seem
P. ginseng, C. A. Meyer
P. japonicas, C. A. Meyer
P. quinquefolius L.
P. vietnamensis, Ha and Grushv
P. wangianus, S. C. Sun
P. zingiberensis, C. Y. Wu and Feng
Notoginseng P. notoginseng, (Burk), F. H. Chen.
Pseudoginseng P. pseudoginseng, Wall
P. stipuleanatus, H. T. Tsai and Feng
Trifolius P. trifolius L.
Zhu zishen, Feather-leaf bamboo ginseng
Chinese ginseng, Korean ginseng, red ginseng, renshen
Japanese ginseng
American ginseng
Vietnamese ginseng, bamboo ginseng
Narrow-leaved pseudoginseng
Ginger ginseng, ginger-like pseudo-ginseng
Tien-qi, Sanchi ginseng, three-seven root
Himalayan ginseng
Pingpien ginseng
Dwarf ginseng, groundnut

and protopanaxatriol (PPT; e.g., Re, Rf, Rg1, Rg2, Rh1)
(Choi, 2008; WHO, 2009). Figure 50.2 shows the chemi-
cal structure of ginsenosides. Ginsenoside Ro and poly-
acetylene ginsenoside-Ro are the only oleanoic acid-type
saponins identified (Zhang et al., 2002). Ginsengosides
can also be used as chromatographic makers for identi-
fication and quality control of the ginseng species. For
example, Ginsenoside Rf is only found in P. ginseng,
not in P. quinquefolius (Fuzzati, 2004). P. quinquefolium
is found to have a higher level of the ginsenoside Rb1,
Re, and Rd than P. ginseng. P. ginseng contains 38 differ-
ent ginsenosides and P. quinquefolius only has 19 (Choi,
2008). Furthermore, P. ginseng also contains more non-
saponin active substances such as compound K, acid
polysaccharides, and polyethylene compounds (Attele
et al., 1999), which are considered more beneficial to
health than P. quinquefolius.
Age, root dry weight, soil fertility, light, and loca-
tion of growth are factors that can affect ginsenoside
contents. Fresh ginseng harvested at less than 4 years
is of least pharmacological interest. It can be used as
a cooking ingredient. The root of P. ginseng harvested
after 5 years or more contains approximately 12% gin-
senosides (Bucci, 2000; Hong et al., 2012). The content
and compositions of ginsenosides in the roots also vary
with processing methods (Gui and Ryu, 2014; Kim,
2015). Ginseng for medicinal use is made into white
and red ginseng, each with different properties. White
ginseng is produced by peeling followed by sun-drying
a 4- to 6-year-old ginseng root. Red ginseng, harvested at
6 years or older, requires repetitive steaming of the fresh
ginseng root at 98100C for 23h; it is then dried until
the moisture content is reduced to less than 15% (Awang
and Li, 2008; Gui and Ryu, 2014; Kim, 2015). Table 50.2
shows the different types of ginsenosides present in
white and red ginseng.
Ginsenosides are generally acid-labile; therefore,
acidic hydrolysis usually occurs with other side reac-
tions like cyclization of side chains and deglycosylation,
followed by chemical transformations of secondary
metabolites during steaming (Yun, 2003). Steaming con-
verts ginsenosides partially to the deglycosylated deriv-
atives. Deglycosylated ginsenosides are reported to be
more bioavailable in humans and result in red ginseng
having better pharmacological functions (Hong et al.,
2011; Hasegawa, 2004). Another compound, malonyl
ginsenosides, such as malonyl ginsenosides Rb1, Rb2,
Rc, and Rd are thermally unstable and can be completely
transformed into the corresponding ginsenosides Rb1,
Rb2, Rc, and Rd after steaming (Fuzzati, 2004). Malonyl
ginsenosides are more abundant in white ginseng than
in red ginseng.
THE HEALTH BENEFITS OF GINSENG
The ancient Chinese pharmacopeia, Shen Nong Ben
Cao Jing (300 BC200 AD), described ginseng as a root
with some resemblance to human form (Figure 50.1), and
thus it is able to nourish all body organs, stabilize the
soul, calm the nerves and spirit, remove bad qi (basic ele-
ment to generate energy and power), improve eyesight,
maintain a cheerful mind, and enhance cognition and
intelligence. Chronic use of Chinese ginseng could help
reduce body weight and prolong life span. According
to traditional Chinese medicinal knowledge, American
ginseng (P. quinquefolius) is a cool or yin tonic used
to treat those suffering from hot symptoms such as
stress, insomnia, palpitations, and headache, whereas
Asian ginseng (P. ginseng) is hot or yang in nature
to invigorate the weakened body (Awan, 1998). Ginseng
is thus considered a panacea acting through balancing

NUTRACEUTICALS
 Biochemical Actions of Ginseng 695

FIGURE 50.2 Chemical structure of different ginsenosides.

the basic elements of the body for optimal health (Park
etal., 2005; Natural Medicines Comprehensive Database,
2014). Yue et al. (2007) suggested that the selected gin-
senosides in ginseng could modulate cellular function
via specific intracellular receptors, thus achieving the
action of homeostasis. In another term, ginseng is con-
sidered an adaptogen (Attele etal., 1999).
BIOCHEMICAL ACTIONS OF GINSENG
Antioxidation is one of the major biochemical
actions of ginsenosides (Gillis, 1997; Kitts and Hu,
2000). Zhang et al. (1996) found that a concentration
of 0.05% ginseng extract can inhibit the conversion of
2,2-diphenyl-1-picrylhydrazyl (DPPH) to its oxidized
form. The same level of ginseng extract was also able
to interrupt the propagation of free radical chain reac-
tion. Kim etal. (2002) also reported that aqueous extract
of red ginseng could quench hydroxyl radicalinduced
DPPH oxidation. Hu and Kitts (2001) demonstrated that
a 30-mg/mL ginseng extract can suppress the oxida-
tion of human low-density lipoprotein when in the pres-
ence of Cu2+, as well as inhibit the cleavage of DNA
via scavenging hydroxyl radical generated through the
Fenton reaction. Ginsenosides Rb1, Rb2, Rb3, Rc, Re,
Rg1, Rg2, and Rh1 all possess significant antioxidant
property (Zhong and Jiang, 1997). Both ginseng extracts
as well as the ginsenoside Rb1 alone were able to pro-
tect breakage of the supercoiled DNA from the attack of

NUTRACEUTICALS
696 50. Chinese Ginseng

TABLE 50.2 Ginsenosides in Panax ginseng weeks, whereas Kim et al. (2011a) reported significant
reduction of lipid peroxidation following administra-
Present in
ginseng (*) tion of a 12g ginseng to healthy participants for the
same period. It must be noted that each ginsenoside
Types of aglycone Ginsenosides White Red might have unique and different potency and function
Protopanaxadiol Ginsenosides Ra1, Ra2, Ra3, * * (Shergis etal., 2013a,b), and interactions among ginsen-
(PPD) Rb1, Rb2, Rb3, Rc, Rd, Rg3 osides would confound the studies, making it difficult
Quinquenoside R1 * * to draw any meaningful conclusion (Zhou etal., 2004).
Besides antioxidant properties, ginsenosides can also
Malonyl-ginsenosides Rb1, *
Rb2, Rc, Rd modulate signaling pathways that regulate cell prolifer-
ation (i.e., the CDKs and cyclins, c-myc, EGFR, vascular
Koryoginsenoside R2 *
endothelial growth factor, tumor suppressors p53 and
Ginsenosides Rg5, Rh2, Rs1, * p21, oncogenes MDM2), cell death (Bcl-2, Bcl-xL, XIAP,
Rs2, Rs3 caspases, and death receptors), inflammatory response
20(S)-ginsenoside Rg3 * molecules (NF-B and COX-2), and many protein kinases
Notoginsenoside R4 * (JNK, Akt, and AMP-activated protein kinase) (Nga etal.,
2012). The action of ginsenosides on the cardiovascular
Protopanaxatriol Ginsenosides Re, Rf, Rg1, * *
(PPT) Rg2, Rh1
system was due to the ability to modify vasomotor func-
tions through reducing platelet adhesion, influencing ion
Ginsenosides Rf2, Rg6, Rh4 *
channels, altering autonomic neurotransmitters release,
Notoginsenoside R1 * * and improving lipid profiles (Kim, 2012). Ginsenosides
20-gluco-ginsenoside Rf * * can also activate cellular release of nitric oxide (NO), a
potent smooth muscle relaxant, to improve physiologi-
Koryoginsenoside R1 *
cal functions ranging from that of the cardiovascular
20(R)-ginsenoside Rg2 * system to sexual performance.
20(R)-ginsenoside Rh1 *
20(E)-ginsenoside F4 *
HEALTH EFFECTS AND
Oleanane Ginsenoside Ro * *
PHARMACOLOGICAL ACTIONS
Polyacetyleneginsenoside Ro *
Chinese ginseng is a nutraceutical that can help
invigorate a weakened body by balancing body func-
peroxyl radicals at a dose-dependent manner (Hu and tions for optimal health (Park et al., 2005). The thera-
Kitts, 2001). Ginsenosides Rb1, Rb2, Rb3, and Rc, but not peutic and pharmacological effects of P. ginseng have
Rd, at 30mg/mL can protect against superoxide radi- been reviewed according to current scientific methods
calinduced damage of cultured cardiac myocytes (Kitts (Attele etal., 1999; Choi, 2008; L etal., 2009; Park etal.,
and Hu, 2000) and ROS-induced damage to pulmonary 2005, 2012; Vogler et al., 1999). Ginseng was found to
endothelium (Gillis, 1997). Besides scavenging free radi- have antidiabetes and anticancer actions and to protect
cals, ginsenosides Rb1 and Rg1 were able to alter hepatic against cardiovascular and nervous system diseases. As
glutathione peroxidase and superoxide dismutase (SOD) a functional food, ginseng can also help improve body
activities and decrease malondialdehyde (MDA) levels strength in exercise and sports, sexual performance, and
(Kitts and Hu, 2000). Ng and Yang (2008) showed that Re relieve menopausal symptoms.
and Rg3 could alter the cellular redox state of cultured
C6 glioma cells in opposite directions through changing
Antidiabetes
the activities of glutathione peroxidase and -glutamyl-
cystienyl synthase, resulting in a change in the intracel- Ginseng has been known to exert hypoglycemic effects
lular reduced/oxidized glutathione ratio, which serves since as early as the 1970s (Yokozawa etal., 1975; Ng and
to reflect the oxidative status of the cell. Despite the Yeung, 1985). Presently, the ginsenosides Rb2 and Rh2,
surmounting evidence that supports the antioxidant protopanaxatriol, (20R)-protopanaxadiol, Rg1, Rc, Rd,
function of ginsenosides, evidence that ginseng could Re, Rf, Rg2, Rh1, and Rb1, and acidic peptide, adenosine,
act as antioxidant in vivo was not clear. The antioxidiz- pyroglutamic acid, and peptidoglycan panaxan B (Choi,
ing effects of P. ginseng on human studies were limited. 2008; Kim et al., 2011b) are found to have antidiabetic
Kim and Lee (2001) were unable to find a significant action. The antidiabetic property of ginseng was mainly
effect in inhibiting MDA-induced lipid peroxidation investigated in STZ-induced type 1 diabetic animal mod-
after administering 1.8g red ginseng to smokers for 4 els (Lai etal., 2006; Lee et al., 2007; Park etal., 2003, 2005).

NUTRACEUTICALS
 Health Effects and Pharmacological Actions
In these studies, red ginseng was found to be supe-
rior over white ginseng and P. quinquefolius (Park etal.,
2003). Ginsenoside Rh2 showed its efficacy in improv-
ing diabetes mellitus through reducing blood glucose
level and increasing insulin sensitivity in STZ-induced
diabetic rats (Lai et al., 2006; Lee et al., 2007). Xiang
et al. (2008) also showed that ginsenoside Re had an
antidiabetic effect in mice. Malonylginsenosides in white
ginseng were reported to have hypoglycemic effects in
these animals (Liu etal., 2009). The possible action was
by accelerating hepatic lipogenesis and increasing glyco-
gen storage (Yokozawa etal., 1975; Oshima etal., 1985;
Sotaniemi etal., 1995). Other studies indicated that the
antidiabetic action of ginsenosides might be related to
other molecules such as adenosine and pyroglutamic,
which could act as insulin-like substances (Choi, 2008;
Kimura and Okuda, 2002).
The clinical efficacy of administering ginseng orally
to the more prevalent type 2 diabetic patients has been
reported (Kim et al., 2011b; Kimura and Okuda, 2002;
Park etal., 2005; Shishtar etal., 2014). Kim etal. (2011b)
reviewed 526 publications, of which four were on ran-
domized human studies on the use of ginseng. The
authors concluded that there was no convincing evi-
dence supporting the efficacy of ginseng in controlling
blood glucose level in type 2 diabetes using extracts from
6-year-old red ginseng. Lee and Son (2011) also found
variable results in other studies (Vuksan et al., 2008;
Sievenpiper etal., 2003; Shishtar etal., 2014) concerning
the ability of ginsenosides to improve glucose metabo-
lism in type 2 diabetic patients. Despite these uncertain-
ties, the current suggested antidiabetic dose of ginseng
is 200mg per day (Natural Medicines Comprehensive
Database, 2014), which is much lower than the dosages
being administered in previous literature studies of 780
and 6000mg of red ginseng concentrate or 2.7g red gin-
seng (Kim et al., 2011b), or 212g of 4-year-old white
ginseng powder (Shishtar etal., 2014).
Protection Against Cardiovascular Diseases
Approximately 40 ginsenosides have been identified
to possess cardiovascular effects. Among them, gin-
senosides Rb1, Rg1, Rg3, Rh1, Re, and Rd have been
extensively studied. The pharmacological effects of
ginsenosides include regulating blood pressure (Caron
et al., 2002), inhibition of platelet aggregation (Kitts
and Hu, 2000), preventing the formation of atheroscle-
rotic plaque formation and various vascular injuries
(Zhou et al., 2004), lowering low-density lipoprotein,
and increasing high-density lipoprotein levels (Park
etal., 2005). The hypotensive effects of ginseng on car-
diovascular function have been shown to related to its
ability to increase blood NO, causing vasorelaxation
(Gillis, 1997; Kim, 2012; Yue et al., 2007). NO can also
NUTRACEUTICALS
697
relieve cardiovascular burden by causing relaxation of
tracheal and bronchial smooth muscle and pulmonary
arteries (Han etal., 2005). Ginsenoside Rg3 can cause a
relaxation of smooth muscle through induction of NO
synthase activity (Xiang et al., 2008). Chen et al. (2008)
showed that ginsenoside Rb1 can cause relaxation of
smooth muscle via acting as a CNS depressant. On the
contrary, Rg1 was reported to cause vasoconstriction
and an increase in blood pressure (Gillis, 1997), possi-
bly via CNS stimulation and cortisol stimulation as well
as endothelin degradation, leading to sodium-induced
fluid retention and vasoconstriction, respectively (Caron
et al., 2002). Another study reported that ginsenosides
protected against myocardial reperfusion damage with
a concomitant increase in 6-keto-prostaglandin F1a and
a decrease in lipid peroxidation (Chen, 1996).
The cardioprotection function of ginseng was not
fully supported in clinical studies. Kim and Lee (2001)
did not find a significant effect on improving triglyceride
and cholesterol levels after smokers were given 1.8g red
ginseng for 4 weeks. In a systematic review, Lee and
Son (2011) found that there was moderate evidence that
supported the use of ginseng in the treatment of cardiac
diseases. Of the four studies on P. ginseng, only one was
conducted in healthy participants and can be scored as
high-quality (Caron etal., 2002). The study showed that
in 30 healthy adult participants there was an increase in
QTc interval and a decrease in diastolic blood pressure
2h after administration of 200mg P. ginseng (Caron etal.,
2002). In addition, no electrocardiographic effect was
found at any other time during a 28-day study period.
Anticancer
The anticancer action of ginsenosides was reviewed
in detail (Nga et al., 2012). The anticancer potency of
ginsenosides depends on the molecular structure, ste-
reo-specificity, the number of sugar molecules that are
attached to the specific position of the saponine skeleton
(Nga etal., 2012). The steaming process, which can con-
vert ginsenosides Rg3, Rg5, and Rh2 to partially degly-
cosylated derivatives, could enhance their uptake and
thus improve anticancer activity (Awang and Li, 2008;
Gui and Ryu, 2014). Polyacetylene compounds such as
panaxydol, panaxynol, and panaxytriol are also found
to have inhibitory effects on cancer cell growth (Choi,
2008). Ginsenoside Rg3, Rg5, and their mixture appeared
to be the active components with anticarcinogenic activ-
ity; ginsenoside Rh2 could potentially inhibit the inci-
dence of tumors (Yun, 2003).
The possible molecular mechanisms involve the
actions of the molecule on different signaling path-
ways that can lead to antiangiogenesis, antimetastasis,
and cancer cell apoptosis (Kitts and Hu, 2000; Yang
et al., 2011; Kim, 2015). Aberrant angiogenesis is an
698 50. Chinese Ginseng
essential step for the progression of solid tumors. The
(20R)-ginsenoside Rg3 has been shown to inhibit the
proliferation of human umbilical vein endothelial cells
(HUVEC) at IC50 of 10nM to form channels in a matrigel
experiment, demonstrating its ability to inhibit vascular
proliferation and thus suppressing angiogenesis (Yue
et al., 2007). The action was due to a decrease in the
matrix metalloproteinase activities (Yue etal., 2007). Yun
(2003) showed that administration of extract of 6-year-
old red ginseng can significantly decrease the incidence
of lung adenoma and liver cancer in mice. No inhibition
of lung tumor incidence in mice was found following
the administration of fresh ginseng younger than 5 years
old. A 10-day treatment with 50400mg red ginseng per
kg body mass in mice was found to inhibit tumor activi-
ties in a dose-dependent manner (Chen etal., 1998).
Metastasis occurs when malignant cells travel through
and penetrate into the blood, lymph, spinal cord, or a
cavity in the body (Park etal., 2005). The lung metastasis
of two different tumor cells in mice was inhibited by 20
(R)- and 20 (S)-ginsenoside-Rg3 obtained from 6-year-old
red ginseng by inhibiting the adhesion and invasion of
tumor cells (Mochizuki etal., 1995). Both intravenous and
oral administrations at doses of 1001000g per mouse
of ginsenoside Rb2, 20 (R)-, and 20 (S)-ginsenoside-Rg3
were effective in inhibiting lung metastasis of B16-B16
melanoma and colon 26-M3.1 carcinoma cells. However,
ginsenoside Rb2 did not exhibit the inhibitory effect on
colon 26-M3.1 when administrated orally and on tumor
cell adhesion in vitro. The suggestions that oral adminis-
tration of 20 (R)- and 20 (S)-ginsenoside-Rg3 for antime-
tastasis with the inhibition of the tumor cell invasion and
adhesion as well as tumor-induced angiogenesis are not
clear and need further investigation (Park et al., 2005).
Xiang etal. (2008) also found that ginsenosides Rb2, Rc,
Rg3, Rg1, and Re can inhibit lung tumor metastasis and
tumor-associated angiogenesis in B16-BL6 melanoma
cells, inducing c-Fos expression in MCF-7 cells, inhibit-
ing the proliferation and suppressing the capillary tube
formation in HUVEC. The actions of these ginsenosides
were associated with antiapoptosis via increasing mem-
brane fluidity in rats, and protection against methyl-
4-phenyl-1,2,3,6-tetrahydropyridine induced apoptosis
in mouse.
Besides animal studies, the administration of gin-
seng for human cancer prevention was also studied. In
a long-term case-controlled study including 1,987 pairs
of Korean participants, red ginseng was shown to have
an inverse dose-response relationship between the risk
of cancers and the frequency and duration of intake.
Significant reductions in many different types of malig-
nancies, including lung, colorectal, and other cancers,
were found (Yun, 2003). However, no association was
found between the ginseng intake and the cancers of
NUTRACEUTICALS
breast, cervix, urinary bladder, and thyroid gland in
females. Another questionnaire-type cohort study with
2,362 male and 2,272 females in Korea found that fresh
ginseng extract decreased relative risk with increased
intake frequency of ginseng, and no cancer death was
reported following the administration of red ginseng
(Yun, 2003). Kim (2015) questioned the validity of many
human studies because the quality of ginseng used
and the reporting were not of international standards.
Further clinical studies with specification of the part of
ginseng extract or the type of ginseng may be required
to verify any merit of ginseng for anticancer activities.
Neurological Effects
The efficacy of P. ginseng on the brain and nervous
system has been reviewed (Choi, 2008; Choi etal., 2013;
Coleman et al., 2003; Geng et al., 2010; Kitts and Hu,
2000; Lee etal., 2009; Park etal., 2005). Administration of
100mg of the standard ginseng extract, G115, twice daily
to a group of 16 health male volunteers over a 12-week
experimental period was able to improve psychomo-
tor functions such as attention, information processing,
integrated sensory-motor function, and auditory reac-
tion time when compared to the baseline. However, the
group performed better than the placebo group only in
the information processing task, but no difference was
found between the two groups regarding the impaired
motor function, recognition, and visual reaction time
(DAngelo etal., 1986).
A series of placebo-controlled trials was conducted
on administrating a single dose of G115 extract alone
(Kennedy etal., 2001) or in combination with other natural
products including ginkgo (Kennedy etal., 2002; Scholey
and Kennedy, 2002) and guarana extract (Kennedy etal.,
2004) on mood and different aspects of cognitive perfor-
mance in healthy volunteers. Kennedy etal. (2001) found
that treatment with 400mg of ginseng extract was able to
improve the quality of memory and secondary memory
performance up to 6h after the dose. Both 200- and 600-
mg ginseng extracts were associated with a significant
improvement in attention speed in 20 healthy participants.
In another study, 20 healthy participants were found to
have improved secondary memory performance, speed
of performing memory tasks, and accuracy of attentional
tasks following 400mg of ginseng extract (Kennedy etal.,
2002). However, improvements in a self-reported state of
mood were found following 360mg of ginkgo and to a
lesser extent the 960mg of ginkgo/ginseng product, but
not in 400mg of ginseng extract alone (Kennedy et al.,
2002). Kennedy et al. (2004) found that 200mg of gin-
seng extract improved cognitive performance in terms
of shortening the speed during the attention task and
memory task, with little evidence of accuracy, up to 6h
 Toxicity of Ginseng
after ginseng intake when compared to placebo in 28
healthy young participants. The quality of interpretation
bias of a controlled trial is of concern. Another study from
Srensen and Sonne (1996) reported that amongst 112
healthy volunteers, positive changes in cognitive function
were found in the ginseng group of 55 (compared with a
placebo group of 57 participants). However, concentra-
tion, memory, and subjective experience in the middle-
aged participants were comparable between ginseng and
placebo groups (Srensen and Sonne, 1996).
P. ginseng is considered to be a stimulant in cogni-
tion. Xiang etal. (2008) summarized mainly from animal
studies that ginsenosides Rb1, Rc, Rg3, Rg1, and Rg2
had effects on the central nervous system (CNS). Both
ginsenosides Rg1 and Rb1 enhanced activities of CNS,
whereas ginsenoside Rb1 had a much weaker potency.
The improvement of cognitive performance was attrib-
uted to the higher ratio of ginsenoside Rg1/Rb1 (Chen
et al., 2008). Ginsenosides Rg1 and Rb1 also helped
to facilitate acquisition and retrieval of memory (Wee
etal., 2011).
A systematic review by Geng etal. (2010) suggested
that panaxydol and panaxynol may have an antiapoptotic
effect in reducing neurodegeneration. Ginsenosides Re,
Rg1, Rg3, and Rh2 may attenuate Alzheimers associated
amyloid peptide accumulation, with Rg3 doing so in
a dose-dependent manner. In addition, ginsenoside Rg2
may have antioxidizing actions in Alzheimers disease
(AD) to protect memory impairment and modulate gene
expression associated with apoptosis to treat vascular
dementia or other ischemia (Geng etal., 2010). Lee and
Son (2011) concluded from eight trials that the strength
of evidence of P. ginseng on psychomotor function was
strong; of these eight trials, six were scored as good qual-
ity and provided doses of P. ginseng extract between 0.2
0.6g to healthy participants. Dose-dependent response
was also found in two studies (Kennedy et al., 2001;
Scholey and Kennedy, 2002). Regarding the improve-
ment of cognitive performance, better concentration and
attention, calmness, and reduced mental fatigue during
mental stress in healthy participants or subjects with AD
were evaluated (Lee and Son, 2011). Wee etal. (2011) also
suggested that ginsenosides Rg1 and Rb1 may reverse
memory loss and cognitive deficit under medical condi-
tions like cerebral ischemia and dementia. Moreover,
ginsenoside Rg1, Rg3, and Re were found to reduce
-amyloid peptide in animal brains following a single
dose (Chen etal., 2006).
Other Health Effects
Sexual Performance
P. ginseng is used to treat erectile dysfunction in males.
The suggested dose of P. ginseng extract for erectile
NUTRACEUTICALS
699
dysfunction is 900mg three times per day (Natural
Medicines Comprehensive Database, 2014). Seven high-
quality clinical trials conducted by RCTS, Inc. reported
no or mild responses to treatment with red ginseng
extract over a dose range of 1.83g per day for up to 12
weeks (Jang et al., 2008; Lee and Son, 2011). Thus, the
support was considered moderate and further studies
are needed.
Exercise and Sports
Approximately 85% of elite track and field athletes
use dietary supplements as part of their regular training
or competition routine (Maughan et al., 2007). There is
a strong interest in using ginseng to enhance physical
performance in competitive sports. The potential ben-
efit to exercise performance is thought to result from
an increase in production of NO (Murphy and Lee,
2002). More recently, Lee and Son (2011) reviewed seven
studies in which ginseng was administered to healthy
athletes at a dose of 3g or ginseng extract 200400mg
per day for 3 or 8 weeks. Neither ginseng nor ginseng
extract showed strong evidence regarding enhancement
of physical performance indicated by studies of aero-
bic and anaerobic performance, lactate threshold, heart
rate recovery, postexercise secretary immunoglobulin A
level, recovery from short and supramaximal exercise,
and energy metabolism (Lee and Son, 2011).
Relieving Menopausal Symptoms
The use of P. ginseng in the relief of menopausal symp-
toms in women was also suggested. Ginsenosides, simi-
lar in structure to hormones, might act through binding
with steroid hormone receptors, including estrogen and
progesterone receptors, to modulate menopausal func-
tions (Yue etal., 2007). A systematic review focused on
a group of 40- to 65-year-old women showed that sexual
arousal, relief of depression, and improved well-being
occurred following red ginseng extract of either 300mg
for 8 weeks or 3,000mg for 12 weeks. Menopausal symp-
toms were also relieved following 200mg G115 for 16
weeks. Nevertheless, these studies had a high risk of
bias and the evidence of using ginseng for managing
menopause was not conclusive (Kim etal., 2013).
TOXICITY OF GINSENG
Toxic Effects
Ginseng is a relatively safe substance with few
adverse effects (IARC Working Group on the Evaluation
of Carcinogenic Risks to Humans, 2002) at a daily dose
between 3 and 9g of powdered ginseng root (Bucci, 2000)
or 200400mg ginseng extract (Dunnick and Nyska,
TABLE 50.3Reports of Adverse Effects

Sex-related
References Cognition Exercise functions Glucose metabolism CVD Cancer Others
a
Jang etal. (2008) 5 (7) studies,
337M, 12 AE
Lee etal. (2009) 2 (2) study,
88M & F, 16 AE
Kim etal. (2011b) 1 (4) studies,
19M & F, 1 AE
Lee and Son (2011)b 2 (8) studies, 3 (8) studies, 4 (7) studies, 2 (7) studies, 4 (5) studies, 1 (2) study for
158M & F, 7 AE 88M & F, 6 AE 190M, 6 AE 58M & F, 1 AE 590M & F, 1 AE pulmonary, 100M &
F, 0 AE
1 (2) study for
cerebrovascular, 10M,
0 AE
Choi etal. (2013) 1 (1) study, 4 (6) studies, 0 (2) study, 0 (1) study, 1 (4) study, 1 (1) study for weight
50M & F, 0 AE 119M, 14 AE 34M & F unknown subject 23M & F; 0 AE management, 45F,
number 0 AE
0 (1) study for 1 (1) study for dry
metabolic syndrome, mouth, 90M & F; 7 AE
23M & F
0 (1) study for
glaucoma, 18M & F
0 (1) study for gastric
problem, 67M & F
Kim etal. (2013) 3 (4) studies, 442F,
131 AE
Shergis etal. (2013a) 6 (17) studies, 8 (10) studies, 4 (4) studies, 4 (9) studies, 7 (8) studies, 2 (2) studies, 3 (5) studies for
232M & F, 12 AE 137M & F, 10 AE 180M, 7 AE 99M & F, 4 AE 160M & F, 8 AE 347M & F, 19 AE respiratory, 198M &
F, 9 AE
1 (4) study for 2 (3) studies, 0 (5) study for
quality of life, 82F, 9 AE immunomodulation,
240M & F, 6 AE 69M & F
1 (2) study, 55M &
F, 3 AE
a
n: number of studies with adverse events stated (number of studies).
b
AE not specified from ginseng and control group; AE, adverse events on ginseng group; CVD, cardiovascular diseases; F, female; M, male.
 Toxicity of Ginseng
2013). Toxic effects may appear with increased admin-
istered doses. A report by Siegel (1979) showed that 14
out of 133 participants suffered from adverse symptoms
following exposure to 15g/day ginseng over a 2-year
period. Nausea and vomiting were reported by a healthy
participant 3 weeks after using 200mg ginseng in a study
on cardiac function (Caron etal., 2002). Hypoglycemia,
tachycardia, headache, blurry vision, insomnia, and irri-
tability were reported in type 2 diabetic patients using
red ginseng (Kim etal., 2011b). Symptoms ranging from
mild discomforts to gastrointestinal problems such as
nausea, vomiting, gastric upset, constipation, or diar-
rhea have been reported in human studies (Lee and Son,
2011). In addition, hypoglycemic symptoms have been
reported in participants with type 2 diabetes following
administration of 6g of red ginseng for 12 weeks (Lee
and Son, 2011; Vuksan etal., 2008). Other adverse events
such as hyperglycemia (Sievenpiper et al., 2004) and
increase in heart rate and blood pressure (Posadzki etal.,
2013b) were also reported. The withdraw rate of patients
enrolled in clinical trials due to adverse events was less
than 10% (Table 50.3), comparable to that of the placebo
group.
DrugHerb Interaction
A review by Posadzki etal. (2013a) showed that gin-
seng can interact with conventional drugs for treatment
of some diseases. It can act synergistically with drugs
that are used for treatment of depression and diabetic
mellitus, some hormones, and those for lowering lipids.
It antagonizes the action of anticoagulants, antiplatelet
agents, and diuretics. Ginseng can act synergistically
and antagonistically with antiarrhythmic agents through
interfering with calcium channel blockers. These interac-
tions, however, only raised a minor concern rather than
a serious threat according to the limited current data
(Qi et al., 2011). Some ginsenosides may be useful in
counteracting multidrug resistance in chemotherapy for
cancer patients. Ginsenoside Rh2 was found to potenti-
ate chemotherapeutic drugs in cancer patients (Jia etal.,
2004). Ginsenoside Rh2 was able to sensitize breast can-
cer cells during therapeutic treatment with paclitaxel
(Szakacs etal., 2006). However, the poor oral absorption
of ginsenoside Rh2 may limit its use as a chemopreven-
tion agent (Yang et al., 2011). Table 50.4 shows some
interaction between ginseng and agents used for treat-
ment of some diseases.
Quality Control
Due to the current high demand, wild ginseng has
become rare (Changbai Mountain Academy of Sciences,
2009). Currently, ginseng is mainly cultivated in
NUTRACEUTICALS
701
TABLE 50.4Interactions between Panax ginseng and Synthetic
Drugs
Class of medication Synergism Antagonism
Antiarrhythmias * *
Anticoagulants and antiplatelet agents *
Antidepressant *
Antidiabetics *
Diuretics *
Hormonal agents *
Lipid-lowering agents *
Northeastern China, Korea, and Japan (Park etal., 2005;
Tang and Eisenbrand, 1992; WHO, 1999). To ensure that
cultivated ginseng can meet the global market demands,
pesticides and herbicides are used to minimize possible
losses from insect infestation and wild weeds. A list of
pesticide residues were detected in ginseng-containing
dietary supplements (FDA, 2008) in a pesticide residue
monitoring program in 2003 and 2004 in the United
States. Twenty-six out of 49 ginseng samples purchased
over the Internet or at a retail establishment contained
volatile residues. A number of pesticides were detected
in a Korean domestic product that was made from 4-, 5-,
and 6-year-old ginseng grown for in four different agri-
cultural areas of the Jeonnam province of South Korea,
but only a few, including Tolclofos-m, were declared
(Park etal., 2007). The US Food and Drug Administration
(FDA) also found that 22 out of 31 imported ginseng
samples originating from Canada, Hong Kong, China,
and South Korea in the form of dried root, ground or
powdered root, liquid or powdered extracts or concen-
trates, or finished products shipped in bulk for repack-
ing in the United States all contain volatile pesticide
residues. Pentachloroaniline, quintozene, and penta-
chlorobenzene were on the top of the list in both domes-
tic and imported samples (Table 50.5). Their levels were
comparable in both the domestic and imported products
(FDA, 2008).
Adulteration is another important issue in the gin-
seng market. In October 2014, the FDA issued a warning
against a ginseng product Ginseng Kianpi Pil (FDA,
2014). The product claimed to contain ginseng root oil as
the active ingredient to relieve fatigue, improve natural
resistance of the body against diseases, and develop an
ideal physique (US National Library of Medicine, 2014),
all consistent with the beneficial effects of ginseng on
the CNS, immune function, and weight management.
The analysis from the FDA laboratory, however, also
detected dexamethasone (a synthetic corticosteroid) and
702 50. Chinese Ginseng

TABLE 50.5 Volatile Residues in Domestic and Imported conditions, making it difficult to obtain uniform crops
Ginseng in USA with a specified content of selected ginsenosides. The
Domestic (26a) Imported (22a) mode of preparation of the plant extracts also affects
the standard and quantity of its active ingredients. As a
No. of samples detected to result, it is often difficult to obtain a standard product
Volatile residues contain the volatile residue
and reduce the variations in treatment efficacies. Nga
Qunitozene 20 16 etal. (2012) proposed that a design of a systematic study
Pentachloroaniline 16 15 on a series of ginsenosides should be established using
current computer technologies to record and integrate
Total BHCs (alpha, beta, delta 13 12
lindane) the vast amount of information on ginseng. Moreover,
methods could be developed to design semi-synthetic
Pentachlorobenzene 12 15
ginsenosides to simulate the pharmacokinetics and bio-
Pentachlorophenyl methyl sulfide 11 10 availability profiles. This suggestion could potentially
Tecnazene 10 7 lead to the development of a new group of pharmaceu-
tical agents.
HCB (Hexachlorobenzene) 12 9
In the meantime, because of its safety records, gin-
2,3,5,6-Tetrachloroaniline 8 7 seng has been developed into a nutraceutical approved
1,2,3,5-Tetrachlorobenzene 2 1 for commercial use in many countries. The worldwide
Others: demand of ginseng as of 2009 was US$1.3 billion, with
South Korea being the largest producer, followed by
Difenoconazole
China, Canada, and the United States (Baeg and So,
Chinaymidone 2013). Studies on the methods of cultivation would
DDE be important to obtain enough raw plants to meet the
Fluvalinate
demand. Besides methods to ensure production of gin-
seng plants containing specific patterns of ginsenosides,
Data extracted from FDA 2008.
a
Total number of samples tested.
reducing the need for pesticides and herbicides used
and techniques for harvesting, processing, and packag-
ing are all important steps to ensure the quality of the
nutraceutical products. Finally, firm regulations must be
instituted among the pharmaceutical industries to pre-
cyproheptadine (an antihistamine drug) in the product vent unscrupulous manufacturers to add, substitute, or
that were not declared on the label (FDA, 2014). adulterate unwanted drugs or chemicals to achieve the
required function of ginseng.

CONCLUDING REMARKS AND FUTURE

DIRECTIONS
Ginseng is a medicinal herb that has been used in
Asian countries for treatment of diseases as well as
improving physiological and psychological well-being
for more than 2,000 years. Ginseng contains many chem-
ical substances, among which ginsenosides are the major
active ingredients. More than 30 different ginsenosides
have been identified, each with characteristic biochemi-
cal actions such as antioxidation, stimulating NO pro-
duction, and modulating different signaling pathways,
resulting in a wide range of therapeutic actions, includ-
ing antidiabetes, anticancer, and antiaging, improving
cardiovascular function, antifatigue action, and improv-
ing sexual performance. The diversity in chemical struc-
ture and biological activities has led to some challenges.
Different species of ginseng have different saponin pro-
files, which may also vary depending on the growth
References
Attele, A.S., Wu, J.A., Yuan, C.S., 1999. Ginseng pharmacology: mul-
tiple constituents and multiple actions. Biochem. Pharmacol. 58
(11), 16851693.
Awan, D.V.C., 1998. The anti-stress potential of North American gin-
seng. J. Herbs Spices Med. Plants 6, 8791.
Awang, D.V.C., Li, M.Z.C., 2008. The pharmacologically active con-
stituents of white and red ginseng root. HerbalGram 80, 3849.
Baeg, I.H., So, S.H., 2013. The world ginseng market and the ginseng
(Korea). J. Ginseng Res. 37, 17.
Bucci, L.R., 2000. Selected herbals and human exercise performance.
Am. J. Clin. Nutr. 72 (2 Suppl.), 624s636s.
Caron, M.F., Hotsko, A.L., Robertson, S., Mandybur, L., Kluger, J.,
White, C.M., 2002. Electrocardiographic and hemodynamic effects
of Panax ginseng. Ann. Pharmacother 36, 758763.
Changbai Mountain Academy of Sciences, 2009. Impacts and
Countermeasures of Global Climate Changes on Alpine Areas.
UNESCO, Jilin Province, China.
Chen, C.F., Chiou, W.F., Zhang, J.T., 2008. Comparison of the pharma-
cological effects of Panax ginseng and Panax quinquefolium. Acta
Pharmacol. Sin. 29, 11031108.

NUTRACEUTICALS
 REFERENCES
Chen, F., Eckman, E.A., Eckman, C.B., 2006. Reductions in levels of
the Alzheimers amyloid beta peptide after oral administration
of ginsenosides. Faseb J. 20, 12691271.
Chen, X., 1996. Cardiovascular protection by ginsenosides and their
nitric oxide releasing action. Clin. Exp. Pharmacol. Physiol. 23,
728732.
Chen, X., Liu, H., Lei, X., Fu, Z., etal., 1998. Cancer chemopreventive
and therapeutic activities of red ginseng. J. Ethnopharmacol. 60,
7178.
Choi, J., Kim, T.H., Choi, T.Y., Lee, M.S., 2013. Ginseng for health care:
a systematic review of randomized controlled trials in Korean
literature. PLoS One 8, e59978.
Choi, K.T., 2008. Botanical characteristics, pharmacological effects and
medicinal components of Korean Panax ginseng C.A. Meyer. Acta
Pharmacol. Sin. 29, 11091118.
Coleman, C.I., Hebert, J.H., Reddy, P., 2003. The effects of Panax ginseng
on quality of life. J. Clin. Pharm. Ther. 28, 515.
DAngelo, L., Grimaldi, R., Caravaggi, M., Marcoli, M., Perucca, E.,
Lecchini, S., etal., 1986. A double-blind, placebo-controlled clini-
cal study on the effect of a standardized ginseng extract on psy-
chomotor performance in healthy volunteers. J. Ethnopharmacol.
16, 1522.
Dunnick, J.K., Nyska, A., 2013. The toxicity and pathology of selected
dietary herbal medicines. Toxicol. Pathol. 41, 374386.
FDA, 2008. Ginseng Dietary Supplements Special Survey (CFSAN
Assignments and Field Regulatory Monitoring for FY 2003 and
FY 2004). Retrieved February 11, 2015, from http://www.fda.gov/
Food/FoodborneIllnessContaminants/Pesticides/ucm116752.
htm#attach1.
FDA, 2014. Ginseng Kianpi Pil: Public Notification Undeclared Drug
Ingredients. Retrieved February 11, 2015, from http://www.fda.
gov/safety/medwatch/safetyinformation/safetyalertsforhu-
manmedicalproducts/ucm421303.htm.
Fuzzati, N., 2004. Analysis methods of ginsenosides. J. Chromatogr. B
812 (12), 119133.
Gardner, Z., McGuffin, M., 2013. American Herbal Products
Associations Botanical Safety Handbook, second ed. CRC Press.
Geng, J., Dong, J., Ni, H., Lee, M.S., Wu, T., Jiang, K., etal., 2010. Ginseng
for cognition. Cochrane Database Syst. Rev. (12), Cd007769.
Gillis, C.N., 1997. Panax ginseng pharmacology: a nitric oxide link?
Biochem. Pharmacol. 54 (1), 18.
Gui, Y., Ryu, G.-H., 2014. Effects of extrusion cooking on physicochemi-
cal properties of white and red ginseng (powder). J. Ginseng. Res.
38, 146153.
Han, K., Shin, I.C., Choi, K.J., Yun, Y.P., Hong, J.T., Oh, K.W., 2005.
Korea red ginseng water extract increases nitric oxide concentra-
tions in exhaled breath. Nitric Oxide 12, 159162.
Hasegawa, H., 2004. Proof of the mysterious efficacy of ginseng: basic
and clinical trials: metabolic activation of ginsenoside: deglyco-
sylation by intestinal bacteria and esterification with fatty acid.
J. Pharmacol. Sci. 95, 153157.
Hong, H.D., Cho, C.W., Kim, Y.C., Kim, E., Rhee, Y.K., Rho, J., et al.,
2012. Morphological characteristics of Korean dried ginseng prod-
ucts. J. Ginseng. Res. 36, 314321.
Hong, S.Y., Oh, J.H., Lee, I., 2011. Simultaneous enrichment of degly-
cosylated ginsenosides and monacolin K in red ginseng by fer-
mentation with Monascus pilosus. Biosci. Biotechnol. Biochem. 75,
14901495.
Hu, C., Kitts, D.D., 2001. Free radical scavenging capacity as related
to antioxidant activity and ginsenoside composition of Asian
and North American ginseng extracts. J. Am. Oil Chem. Soc. 78,
249255.
NUTRACEUTICALS
703
IARC Working Group on the Evaluation of Carcinogenic Risks to
Humans, 2002. Some traditional herbal medicines, some myco-
toxins, naphthalene and styrene. IARC Monogr. Eval. Carcinog.
Risks Hum. 82, 1556.
Jang, D.J., Lee, M.S., Shin, B.C., Lee, Y.C., Ernst, E., 2008. Red ginseng
for treating erectile dysfunction: a systematic review. Br. J. Clin.
Pharmacol. 66, 444450.
Jia, W.W., Bu, X., Philips, D., Yan, H., Liu, G., Chen, X., etal., 2004. Rh2,
a compound extracted from ginseng, hypersensitizes multidrug-
resistant tumor cells to chemotherapy. Can. J. Physiol. Pharmacol.
82, 431437.
Kennedy, D.O., Scholey, A.B., Wesnes, K.A., 2001. Dose dependent
changes in cognitive performance and mood following acute
administration of ginseng to healthy young volunteers. Nutr.
Neurosci. 4, 295310.
Kennedy, D.O., Scholey, A.B., Wesnes, K.A., 2002. Modulation of cogni-
tion and mood following administration of single doses of Ginkgo
biloba, ginseng, and a ginkgo/ginseng combination to healthy
young adults. Physiol. Behav. 75, 739751.
Kennedy, D.O., Haskell, C.F., Wesnes, K.A., Scholey, A.B., 2004.
Improved cognitive performance in human volunteers following
administration of guarana (Paullinia cupana) extract: comparison
and interaction with Panax ginseng. Pharmacol. Biochem. Behav.
79, 401411.
Kim, H.G., Yoo, S.R., Park, H.J., Lee, N.H., Shin, J.W., Sathyanath,
2011a. Antioxidant effects of Panax ginseng C.A. Meyer in healthy
subjects: a randomized, placebo-controlled clinical trial. Food
Chem. Toxicol. 49, 22292235.
Kim, S., Shin, B.C., Lee, M.S., Lee, H., Ernst, E., 2011b. Red ginseng
for type 2 diabetes mellitus: a systematic review of randomized
controlled trials. Chin. J. Integr. Med. 17, 937944.
Kim, H.S., Lee, B.M., 2001. Protective effects of antioxidant supple-
mentation on plasma lipid peroxidation in smokers. J. Toxicol.
Environ. Health A 63, 583598.
Kim, J.H., 2012. Cardiovascular diseases and Panax ginseng: a review
on molecular mechanisms and medical applications. J. Ginseng.
Res. 36, 1626.
Kim, K., 2015. Effect of ginseng and ginsenosides on melanogenesis
and their mechanism of action. J. Ginseng. Res. 39, 16.
Kim, M.S., Lim, H.J., Yang, H.J., Lee, M.S., Shin, B.C., Ernst, E., 2013.
Ginseng for managing menopause symptoms: a systematic review
of randomized clinical trials. J. Ginseng. Res. 37, 3036.
Kim, Y.K., Guo, Q., Packer, L., 2002. Free radical scavenging activity of
red ginseng aqueous extracts. Toxicology 172, 149156.
Kimura, Y., Okuda, H., 2002. Biochemical and pharmacological stud-
ies on natural products isolated from various medicinal plants
and foodstuffs. In: Rahman, A. (Ed.), Studies in Natural Products
Chemistry: Bioactive Natural Products, Part H, vol. 27 Elsevier
Science, pp. 393442.
Kitts, D., Hu, C., 2000. Efficacy and safety of ginseng. Public Health
Nutr. 3, 473485.
Lai, D.M., Tu, Y.K., Liu, I.M., Chen, P.F., Cheng, J.T., 2006. Mediation
of beta-endorphin by ginsenoside Rh2 to lower plasma glucose in
streptozotocin-induced diabetic rats. Planta Med. 72, 913.
Lee, M.S., Yang, E.J., Kim, J.I., Ernst, E., 2009. Ginseng for cognitive
function in Alzheimer's disease: a systematic review. J. Alzheimers
Dis. 18, 339344.
Lee, N.H., Son, C.G., 2011. Systematic review of randomized controlled
trials evaluating the efficacy and safety of ginseng. J. Acupunct.
Meridian Stud. 4, 8597.
Lee, W.K., Kao, S.T., Liu, I.M., Cheng, J.T., 2007. Ginsenoside Rh2
is one of the active principles of Panax ginseng root to improve
704 50. Chinese Ginseng
insulin sensitivity in fructose-rich chow-fed rats. Horm. Metab.
Res. 39, 347354.
Liu, C.X., Xiao, P.G., 1992. Recent advances on ginseng research in
China. J. Ethnopharmacol. 36, 2738.
Liu, Z., Wang, L.J., Li, X., Hu, J.N., Chen, Y., Ruan, C.C., et al., 2009.
Hypoglycemic effects of malonyl-ginsenosides extracted from
roots of Panax ginseng on streptozotocin-induced diabetic mice.
Phytother Res. 23, 14261430.
L, J.M., Yao, Q.Z., Chen, C.Y., 2009. Ginseng compounds: an update
on their molecular mechanisms and medical applications. Curr.
Vasc. Pharmacol. 7, 293302.
Maughan, R.J., Depiesse, F., Geyer, H., 2007. The use of dietary supple-
ments by athletes. J. Sports Sci. 25 (Suppl. 1), S103S113.
Mochizuki, M., Yoo, Y.C., Matsuzawa, K., Sato, K., Saiki, I., Tono-oka,
1995. Inhibitory effect of tumor metastasis in mice by saponins,
ginsenoside-Rb2, 20(R)- and 20(S)-ginsenoside-Rg3, of red gin-
seng. Biol. Pharm. Bull. 18, 11971202.
Murphy, L.L., Lee, T.J., 2002. Ginseng, sex behavior, and nitric oxide.
Ann. N.Y. Acad. Sci. 962, 372377.
Natural Medicines Comprehensive Database, 2014. Ginseng, Panax.
Retrieved January 25, 2015, from http://www.nlm.nih.gov/med-
lineplus/druginfo/natural/1000.html.
Ng, T.B., Yeung, H.W., 1985. Hypoglycemic constituents of Panax gin-
seng. Gen. Pharmacol. 16, 549552.
Ng, W.Y., Yang, M.S., 2008. Effects of ginsenosides Re and Rg3 on
intracellular redox state and cell proliferation in C6 glioma cells.
Chi. Med. 3, 816.
Nga, S.A., Qin, J.J., Wang, W., etal., 2012. Ginsenosides as anticancer
agents: in vitro and in vivo activities, structureactivity relation-
ships, and molecular mechanisms of action[J]. Front. Pharmacol.
3, 25.
Oshima, Y., Konno, C., Hikino, H., 1985. Isolation and hypoglycemic
activity of panaxans I, J, K and L, glycans of Panax ginseng roots.
J. Ethanopharmacol. 14, 255259.
Park, H.J., Kim, D.H., Park, S.J., Kim, J.M., Ryu, J.H., 2012. Ginseng
in traditional herbal prescriptions. J. Ginseng. Res. 36, 225241.
Park, J., Rhee, D., Lee, Y., 2005. Biological activities and chemistry
of saponins from Panax ginseng C.A. Meyer. Phytochem. Rev. 4,
159175.
Park, K.S., Ko, S.K., Chung, S.H., 2003. Comparisons of antidiabetic
effect between ginseng Radix Alba, Ginseng Radix Rubra and
Panax Quinquefoli Radix in MLD STZ-induced diabetic rats.
J. Ginseng. Res. 27, 5661.
Park, Y.S., Abd El-Aty, A.M., Choi, J.H., Cho, S.K., Shin, D.H., Shim,
J.H., 2007. Pesticide multiresidue analysis in Panax ginseng (C.A.
Meyer) by solid-phase extraction and gas chromatography with
electron capture and nitrogen-phosphorus detection. Biomed.
Chromatogr. 21, 2939.
Posadzki, P., Watson, L., Ernst, E., 2013a. Herb-drug interactions: an
overview of systematic reviews. Br. J. Clin. Pharmacol. 75, 603618.
Posadzki, P., Watson, L.K., Ernst, E., 2013b. Adverse effects of
herbal medicines: an overview of systematic reviews. Clin. Med.
13, 712.
Qi, L.W., Wang, C.Z., Du, G.J., Zhang, Z.Y., Calway, T., Yuan, C.S., 2011.
Metabolism of ginseng and its interactions with drugs. Curr. Drug
Metab. 12, 818822.
Scholey, A.B., Kennedy, D.O., 2002. Acute, dose-dependent cognitive
effects of Ginkgo biloba, Panax ginseng and their combination in
healthy young volunteers: differential interactions with cognitive
demand. Hum. Psychopharmacol. 17, 3544.
Shergis, J.L., Zhang, A.L., Zhou, W., Xue, C.C., 2013a. Panax ginseng
in randomised controlled trials: a systematic review. Phytother
Res. 27, 949965.
NUTRACEUTICALS
Shergis, J.L., Zhang, A.L., Zhou, W., Xue, C.C., 2013b. Quality and risk
of bias in Panax ginseng randomized controlled trials: a review.
Am. J. Chin. Med. 41, 231252.
Shim, Y.H., Park, C.D., Kim, D.H., Cho, J.H., Cho, M.H., Kim, H.J.,
2005. Identification of Panax species in the herbal medicine prepa-
rations using gradient PCR method. Biol. Pharm. Bull. 28, 671676.
Shishtar, E., Jovanovski, E., Jenkins, A., Vuksan, V., 2014. Effects of
Korean white ginseng (Panax ginseng C.A. Meyer) on vascular
and glycemic health in type 2 diabetes: results of a randomized,
double blind, placebo-controlled, multiple-crossover, acute dose
escalation trial. Clin. Nutr. Res. 3, 8997.
Siegel, R.K., 1979. Ginseng abuse syndrome. Problems with the pana-
cea. J. Am. Med. Assoc. 241, 16141615.
Sievenpiper, J.L., Arnason, J.T., Leiter, L.A., Vuksan, V., 2003. Null and
opposing effects of Asian ginseng (Panax ginseng C.A. Meyer) on
acute glycemia: results of two acute dose escalation studies. J. Am.
Coll. Nutr. 22, 524532.
Sievenpiper, J.L., Arnason, J.T., Leiter, L.A., Vuksan, V., 2004. Decreasing,
null and increasing effects of eight popular types of ginseng on
acute postprandial glycemic indices in healthy humans: the role
of ginsenosides. J. Am. Coll. Nutr. 23, 248258.
Srensen, H., Sonne, J., 1996. A double-masked study of the effects of
ginseng on cognitive functions. Curr. Ther. Res. 57, 959968.
Sotaniemi, E., Haapakoski, E., Rautio, A., 1995. A ginseng therapy
in non-insulin-dependent diabetic patients. Diabetes Care 18,
13731375.
Szakacs, G., Paterson, J.K., Ludwig, J.A., Booth-Genthe, C., Gottesman,
M.M., 2006. Targeting multidrug resistance in cancer. Nat. Rev.
Drug Discov. 5, 219234.
Tang, W., Eisenbrand, G., 1992. Panax ginseng C.A. Meyer Chinese
Drugs of Plant Origin. Springer, Berlin Heidelberg, pp. 711737.
US National Library of Medicine, 2014. Ginseng Kianpi Pil
Angelica sinensis Whole, Morinda officinalis Whole and Panax
ginseng Root Oil Capsule. Retrieved February 10, 2015, from
http://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.
cfm?setid=ee656e9a-abd3-488b-949a-fca2d1a95bf0&type=display.
Vogler, B.K., Pittler, M.H., Ernst, E., 1999. The efficacy of ginseng.
A systematic review of randomised clinical trials. Eur. J. Clin.
Pharmacol. 55, 567575.
Vuksan, V., Sung, M.K., Sievenpiper, J.L., Stavro, P.M., Jenkins, A.L.,
Di Buono, M., et al., 2008. Korean red ginseng (Panax ginseng)
improves glucose and insulin regulation in well-controlled, type
2 diabetes: results of a randomized, double-blind, placebo-con-
trolled study of efficacy and safety. Nutr. Metab. Cardiovasc. Dis.
18, 4656.
Wee, J.J., Mee, P.K., Chung, A.S., 2011. Biological activities of ginseng
and its application to human health. In: Benzie, I.F.F., Wachtel-
Galor, S. (Eds.), Herbal Medicine: Biomolecular and Clinical
Aspects CRC Press LLC, Boca Raton, FL.
WHO, 1999. WHO Monographs on Selected Medicinal Plants, vol. 1.
World Health Organization, Malta.
WHO, 2009. WHO Monographs on Selected Medicinal Plants, vol. 4.
World Health Organization, Geneva, Switzerland.
Xiang, Y.Z., Shang, H.C., Gao, X.M., Zhang, B.L., 2008. A compari-
son of the ancient use of ginseng in traditional Chinese medicine
with modern pharmacological experiments and clinical trials.
Phytother Res. 22, 851858.
Yang, Z., Gao, S., Wang, J., Yin, T., Teng, Y., Wu, B., et al., 2011.
Enhancement of oral bioavailability of 20(S)-ginsenoside Rh2
through improved understanding of its absorption and efflux
mechanisms. Drug Metab. Dispos. 39, 18661872.
Yokozawa, T., Seno, H., Oura, H., 1975. Effect of ginseng extract on
lipid and sugar metabolism. Chem. Pharmacol. 23, 30953100.
 REFERENCES
Yue, P.Y., Mak, N.K., Cheng, Y.K., Leung, K.W., Ng, T.B., Fan, D.T.,
etal., 2007. Pharmacogenomics and the Yin/Yang actions of gin-
seng: anti-tumor, angiomodulating and steroid-like activities of
ginsenosides. Chin. Med. 2, 6.
Yun, T.K., 2001. Panax ginseng a non-organ-specific cancer preven-
tive? Lancet Oncol. 2, 4955.
Yun, T.K., 2003. Experimental and epidemiological evidence on non-
organ specific cancer preventive effect of Korean ginseng and
identification of active compounds. Mutat. Res. 523524, 6374.
Zhang, D., Yasuda, T., Yu, Y., Zheng, P., Kawabata, T., Ma, Y., et al.,
1996. Ginseng extract scavenges hydroxyl radical and protects
705
unsaturated fatty acids from decomposition caused by iron-
mediated lipid peroxidation. Free Radic. Biol. Med. 20,
145150.
Zhang, H.J., Lu, Z.Z., Tan, G.T., Qiu, S.X., Farnsworth, N.R., Pezzuto,
J.M., etal., 2002. Polyacetyleneginsenoside-Ro, a novel triterpene
saponin from Panax ginseng. Tetrahedron Lett. 43, 973977.
Zhong, G., Jiang, Y., 1997. Calcium channel blockage and anti-free-
radical actions of ginsenosides. Chin. Med. J. (Engl) 110, 2829.
Zhou, W., Chai, H., Lin, P.H., Lumsden, A.B., Yao, Q., Chen, C.J., 2004.
Molecular mechanisms and clinical applications of ginseng root
for cardiovascular disease. Med. Sci. Monit. 10, Ra187Ra192.

NUTRACEUTICALS