Curcuma longa

Phytotherapy
SYNONYMS
yellow root, turmeric
EFFECT
Introduction
From time immemorial, the Curcuma longa, the yellow root, has been cultivated in India, Southern China and other tropical and
subtropical countries. It is conjectured that the yellow root originates from East India, but this is not certain because the plant has never
been found in the wild. The plants flower and growth pattern looks very similar to that of ginger and it is also in the same family as ginger
(Zingiberaceae). The yellow root can grow to a height of approximately 1 metre. A bundle of leaves and flower stalk with a 20-cm-long
flower rises from the rootstock. Similarly to the ginger plant, side shoots with corm-like swellings develop underground. The yellow root
grows best in damp and warm areas. The underground parts of the plants are dug up when the flowers wilt in December and January. The
corms and the rootstock are separated from the side shoots. These are then submerged in boiling water and placed in the sun to dry.
Through drying in the sunlight, the under-ground parts become yellow in colour: the heat from the sun causes the pigment from the
glandular cells to be distributed over the rootstock and corms. Once they are dry, the rootstocks are ground to form a powder which is called
curcumin or curcuma. The powder is then sold under the name fumeric.
Species
There are various species of Curcuma. In addition to Curcuma longa the real yellow root there is a Curcuma xanthorrhiza (Temoe
Lawak, Javanese Curcuma root, bitter Curcuma root) and a Curcuma zedoaria (Zedoary root). The Dutch introduced Curcuma xanthorrhiza
to Europe, where it was given the well-known name Temoe Lawak. The Curcuma zedoaria plant originates from the Himalayas, where
the leaves are used in salads.
According to Van Hellemont, the Curcuma xanthorrhiza is preferred as, because of a higher concentration of essential oils, this species has a
more powerful cholagogic and choleretic effect than the Curcuma longa. He says that the Curcuma longa is more popular in cooking and the
Curcuma zedoaria should be seen as more of a stomach remedy. However, research shows that the Curcuma longa does actually have
powerful cholagogic and choleretic properties in addition to numerous other pharmacological properties, which have not yet been
demonstrated in the xanthorrhiza. The WHOs monograph therefore rightly relates to the Curcuma longa and describes its effects as
hepatoprotective (liver cell protection), antioxidant, inflammation inhibitor, and its antibacterial and fungicidal properties (fungicidal).
Traditional medicine
Yellow root is an important seasoning in Indian cuisine; yellow root is one of the principal ingredients of curry. Yellow root not only gives
meals a beautiful, deep yellow colour (popular in rice), but its slightly bitter taste also encourages consumption.
In addition to being appreciated for its culinary uses, yellow root has also been used for a long time in the treatment of liver and bile
problems, jaundice and general digestive symptoms. In addition, in traditional medicine, the plant was also used for arthritis because of its
inflammation-inhibiting properties.
Curcuma is surprisingly versatile
Curcumin, the principal ingredient of the curcuma seasoning, is a likely winner of the cure-all title: a (wonder) remedy that can cure all
ailments. In hundreds of pre-clinical studies, various health-enhancing effects of curcumin have been revealed. The number of human clinical
studies using curcumin is limited; more research is required to find out whether, following oral intake, the therapeutic properties of
curcumin (including the antioxidative and inflammation-inhibiting activity) can be sufficiently expressed, plus the dose required to achieve
that. Curcumin is a promising phytonutrient for the prevention and treatment of a diversity of disorders, such as atherosclerosis, cataracts,
rheumatoid arthritis, gall stones, stomach ulcers, inflammatory bowel diseases, depression and dementia.
Seasoning and phytotherapeutics
The root of curcuma longa (Asian yellow root, curcuma), a plant that belongs to the ginger family, is a favourite and commonly used
seasoning in Eastern cuisine. It gives (curry) meals a mild bitter flavour and a deep-yellow colour. Every day, the Indian population
consumes 2-2.5 grams of dried yellow root (with 60-200 mg of curcuminoids); Westerners use significantly less curcuma in their food. The
monographs that the World Health Organisation and German Commission E have applied to curcuma, recommend curcuma for (functional)
dyspepsia, gall bladder dysfunction (cholestasis, lithogenic bile), peptic ulcer, lack of appetite and rheumatoid arthritis [1,2]. The
recommended dose is 1.5-3 grams of curcuma per day; doses up to 8 grams per day are prescribed for stomach and duodenal ulcers. It is
required that the product contains a minimum of 3% curcuminoids and 4% essential oils.
Properties of curcumin
The therapeutic properties of curcumin were determined in hundreds of in-vitro and animal studies; various reviews describe the cellular,
molecular and biochemical mechanism of action of curcumin [3,5-9]. Briefly summarised: curcumin has antioxidative, inflammationinhibiting, immunomodulating, wound-healing, lipid-lowering, detoxicating, liver protective, uncramping, neuroprotective, digestiveboosting, anti-angiogenic and antimicrobial properties [1,3-7,10-12].
In practice

Depending on the intended effect, extensive clinical research is required in order to determine the effective (preventative, therapeutic) dose of
curcumin. Curcumin has moderate biological availability following oral administration by a fast conjugation in the intestines and liver to
curcumin glucuronides and sulphates or reduction to hexahydrocurcumin. Between 40 and 85% of the curcumin leaves the gastrointestinal
tract with the stools [3,7,8]. For a local effect (in the gastrointestinal tract) this is fine; there are indications that orally administered
curcumin accumulates in the tissues of the gastrointestinal tract. Studies have also revealed that curcumin has systemic effects at a relatively
low dose; for example, a dose of 20 mg of curcumin has a significant effect on gall bladder contraction and serum lipid peroxidation.
Curcumin disappears rapidly from the blood circulation, but also easily passes the blood-brain barrier and can be active there at a relatively
low concentration. Insufficient is known about the biological activity of curcumin metabolites.[3,9].
Active compounds
Essential oils (2-7%) consisting of 60% sesquiterpenes with methyl-p-tolyl carbinol, turmeron, aturmeron, atlanton and zingiberene; orange
colorants such as curcumin (1.5-5.4%), monodesmethoxycurcumin (0.8%), didesmethoxycurcumin (0.5%).
Although the essential oils with mono-sesquiterpenes and sesquiterpenes most certainly contribute to the therapeutic effect of curcuma,
mainly the yellow-orange curcuminoids are responsible for the healing effects of curcuma. Curcuminoids are non-volatile, fat-soluble
polyphenols (dicinnamoylmethane derivatives); 75-80% thereof is curcumin (curcumin I /diferuloylmethane), the remainder comprises
curcumin II (demethoxycurcumin) and curcumin III (bisdemethoxycurcumin) [3,4]. Most research now focuses on curcumin; by using
curcuma extracts with a very high level of curcumin (90-95%), significantly more powerful effects can be achieved than with unprocessed
curcuma (that contains 2-9% curcumin).
Mechanism of action
The traditional medicinal uses seem to be very closely in line with the scientific research that has taken place during the past years into the
plants mechanism of action. The main active ingredients are the curcumin and the essential oils. The monograph of the WHO and Van
Hellemont indicate that cholagogic and choleretic properties of the yellow root can be attributed to the essential oils and the curcumins.
The curcumins appear to:
increase the secretion of bile;
promote the flow of bile to the intestine;
protect the liver (hepatoprotective effect) and support liver function;
raise the level of glutathione in the liver;
stimulate the activity of glutathione S-transferase in the liver;
promote the detoxification of toxic substances;
inhibit blood platelet aggregation;
possess antibiotic properties;
lower the cholesterol level;
possess antioxidative properties;
have a catabolic and metabolic effect on fat absorption;
have inflammation-inhibiting properties;
have a fungicidal effect on, amongst others, Candida albicans.
In the future, scientific research will elaborate on many of the aforementioned properties. Particularly the inflammation-inhibiting properties
receive significant amounts of attention in the treatment of rheumatoid arthritis.
Other interesting actions are the inhibition of blood platelet aggregation and the reduction in the cholesterol level (use in cardiovascular
disorders), hepatoprotective properties (use in detoxicification), choleretic and cholagogic properties (use in gallbladder function disorders
and constipation) and the antibacterial and fungicidal properties.
The most commonly mentioned indications are cholelithiasis, cholecystitis, liver parenchyma damage, icterus and inflammations of the gall
bladder and biliary tracts.

INDICATIONS
Antioxidant
Curcumin is a powerful (fat-soluble) antioxidant and radical scavenger of oxygen radicals and reactive nitrogen particles. Indirectly, curcumin
is responsible for an improved antioxidant defence by a rise in the activity of antioxidant enzymes (glutathione peroxidase, superoxide
dismutase, catalase) and a rise in the glutathione level (the main intracellular antioxidant) by increasing the expression of genes for GCL
(glutamate-cysteine ligase, the rate-limiting enzyme in the glutathione synthesis) [13,14]. Curcumin offers support in disease processes
associated with lipid peroxidation such as atherosclerosis, neurodegenerative illnesses (including Alzheimers disease) and inflammatory
diseases. Animal research demonstrated that curcumin limits ischemia-reperfusion damage in the heart and brain [3,7,9,15]. Curcumin
protects the brain against damage caused by alcohol consumption, whereby a decrease in oxidative stress and lipid peroxidation and an
improvement of the glutathione level in brain tissue is seen. In healthy volunteers, a low oral dose of curcumin (20 mg per day for 75 days)
resulted in a significant fall in serum lipid peroxidation by 60% [17].
Pro-inflammatory eicosanoids
Curcumin inhibits both acute and chronic inflammatory processes. First and foremost this is because curcumin counteracts the formation of
pro-inflammatory eicosanoids (arachidonic acid metabolites). These powerful inflammation mediators occur when arachidonic acid is
released from membrane phospholipids by phospholipase-a2. Arachidonic acid is then converted by the enzymes cOX-2 (cyclooxygenase-2)
and 5-LOX (5-lipoxygenase) into type-2-prostaglandins and type 5 leucotrienes. Laboratory tests have proven that curcumin significantly
inhibits the activity of the enzymes phospholipase-a2, cOX-2 and 5-LOX [3,18]. The fact that curcumin inhibits phospholipase-a2 is very
favourable because cutting loose arachidonic acid from membrane phospholipids is the rate-limiting step in the production of
pro-inflammatory eicosanoids. Pro-inflammatory eicosanoids not only boost typical inflammatory diseases but also neurodegenerative
diseases, diabetes type 2, cardiovascular diseases, auto-immune illnesses and COPD.
Transcripton factor NF-kB
The second equally important way in which curcumin counteracts inflammations is by inhibiting activated NF-kB (nuclear factor kappa-B)
[21]. NF-kB is a group of inducible transcription factors present in almost all of the bodys cells which exercise control over the
transcription of genes that regulate the inflammatory response by producing cytokines, chemokines, adhesion molecules, metalloproteinases
and acute phase proteins. Inflammatory and immune responses are particularly following activation by pathogenic micro-organisms
largely coordinated by NF-kB [22]. NF-kB is responsible for the increase in oxidative stress; activation of NF-kB is, amongst others,
associated with asthma, contact allergy, atherosclerosis, heart failure, ischemic reperfusion, AIDS, septic shock, (rheumatoid) arthritis,

sarcoidosis, COPD, diabetes, Irritable Bowel Disease (IBD) and multiple sclerosis [22-25]. Researchers suspect that an increase in NF-kB
activity is one of the main causes of aging / age-related illnesses and can have an impact on life expectancy; this would mean that curcumin
is an anti-aging substance [3,26,27].
Immunomodulation
In an experimental animal study (for chronic colitis), it was recently demonstrated that curcumin has a regulatory action on the balance
between th1 and th2 cells and the th1/th2 ratio shifts in the direction of th2 cells [28]. T helper cells (lymphocytes) influence the
inflammation process through the type (pro-inflammatory) of cytokines (interleukins, tumour necrosis factor (tNF)) that they produce. In a
healthy defence system, there is a good balance between the th1 and th2 cells.
In th2 mediated immune illnesses such as allergies, the th1/th2 ratio has shifted towards (overactivity of) th2 cells; in th1 mediated
inflammations are the dominating factor of the activity of th1 cells. Curcumin can possibly have an impact on the disease process of th1
medicated immune illnesses such as auto-immune illnesses (rheumatoid arthritis, SLE, scleroderma, diabetes type 1, psoriasis, and
multiple sclerosis), chronic infections, depression and atherosclerosis [3,28,29].
Post-operative inflammation
In a human pilot study it was demonstrated that curcumin combats post-operative swelling and inflammation [30]. Forty-five patients who
had recently undergone groin surgery were given a placebo for five days, curcumin (1,200 mg/day) or phenylbutazone (300 mg/day).
Curcumin and (to a lesser degree) phenylbutazone had a significant inflammation-inhibiting effect with a reduction in pain, sensitivity and
swelling in comparison to the placebo.
Rheumatoid arthritis
Activation of NF-kB probably plays a central role in the disease process of rheumatoid arthritis [3, 22, 31]. Orally administered
curcuminoids (117 mg/kg/day) significantly inhibited the acute and chronic phase of experimental rheumatoid arthritis [31]. As from the
fourth day before >arthritis was induced, laboratory animals were given curcumin. This resulted in 48% inhibition of the acute inflammation
process and 45% inhibition of the chronic degenerative process. The dose of curcuminoids given is comparable to a dose of one gram per
day for people weighing 70 kg. Curcumin supplementation had much less of an effect when it was given just eight days after inducing
arthritis (in the acute phase). In a small double-blind study, 18 people with rheumatoid arthritis were given curcumin for a two-week period
(1,200 mg per day) or an NSAID (300 mg of phenylbutazone per day) [1, 4]. Both curcumin and phenylbutazone significantly reduce
morning stiffness and joint swelling and improved walking.
Inflammatory intestinal disorder
Curcumin was tested in an animal model for inflammatory intestinal disorders (Crohns disease, ulcerative colitis) [32]. The diet of mice
suffering from colitis contained 0.5, 2 or 5% curcumin. Supplementation with curcumin resulted in suppression of NF-kB with a decrease in
proinflammatory cytokines (IL-1 beta, IL-6, tNF alpha, IL-12 and interferon gamma) and a reduction in clinical and histological signs of
mucous membrane inflammation in the large intestine. The study revealed for the first time that treatment with curcumin relieved
experimental colitis in mice and can prevent undernourishment and death. Curcumin (72-144 mg per day) potentially also works in irritable
bowel syndrome (spastic colon) [33]. A non-placebo-controlled pilot study involving 207 people with a spastic colon showed an
improvement after eight weeks of stomach ache, defecation pattern and quality of life.
Depression
In Chinese medicine, curcuma is the main ingredient of the herbal formula against depression. Curcumin is fat-soluble and can effortlessly
pass the blood-brain barrier. In animal models for depression it has been proven that curcumin at an oral dose of 5 and 10 mg/ kg/day can
significantly reduce depressive behaviour [34]. Curcumin inhibits the enzyme monoamine oxidase (MAO) and increases the activity of
serotonin, noradrenaline and dopamine in the brain. The dose of 10 mg/kg/day resulted in a significant rise in the serotonin and
noradrenaline levels in the frontal cortex and hippocampus, as well as in the dopamine level in the frontal cortex and striatum. These brain
areas are important for emotion, motivation, learning and memory.
Infections
Curcuma has a broad antimicrobial activity and inhibits (in-vitro) the growth of gram-positive bacteria (Staphylococcus aureus), viruses
(HIV, human papillomavirus), pathogenic fungi, protozoa (Leishmania, giardia lamblia, trichomonas vaginalis, plasmodium) and worms [1,
3, 5-7, 9-11, 35-39]. It is of importance that curcuma extract (in-vitro) inhibits the MRSA bacteria (Multiresistant Staphylococcus aureus)
and resensitises this to beta lactam antibiotics [40]. In-vitro it has been proven that, at a low concentration, the essential oils of curcuma
inhibit gram-positive bacteria such as Staphylococcus aureus and that this effect is equal to that achieved by ampicillin, doxycycline and
gentamicin [39].
Wound healing
In India, an externally applied paste made from curcuma is a tried and tested home remedy for wounds. Research has confirmed that
curcumin aids wound healing; it stimulates the migration of macrophages, neutrophils and fibroblasts to the wound, accelerates the wound
contraction, stimulates the formation of granulation tissue, supports the formation of new blood vessels (neovascularisation) and improves
re-epithelialisation [3,7,41,42]. Curcumin also accelerates the recovery of wounds that have difficulty healing on account of inflammation,
diabetes, the use of hydrocortisone or radiation [6,7,9,42]. An additional benefit is that curcuma helps to prevent wound infection.
Psoriasis
In a study involving forty psoriasis patients, it was proven that a gel containing 1% curcumin favourably affected the th1 mediated
inflammation process in the skin [43]. In this hyperproliferative inflammatory illness, large numbers of dividing keratinocytes migrate too
quickly towards the skin surface. An increased activity of the phosphorylase kinase enzyme plays a central role in this; this signal molecule
regulates the cell division and cell migration. In the study, it was proven that curcumin is better at counteracting the rise of the
phosphorylase activity than calcipotriol.
Stomach ulcer
Curcuma reduces pain and accelerates the healing of stomach and duodenal ulcers. Apart from the antioxidative and inflammation-inhibiting
action, curcuma is responsible for an improved protective mucous layer [1,9,44,45]. In addition, curcuma is a natural gastric acid inhibitor:
it reduces (histamine-induced) gastric acid secretion by means of dose-dependent competitive binding to h2 histamine receptors; it is not yet
clear which components are responsible for this effect [46]. Curcuma and curcumin (in-vitro) also inhibit the growth and attachment of the
bacteria helicobacter pylori, the bacteria which causes stomach ulcers. Curcumin combats stomach ulcers caused by stress, alcohol, reserpine
and NSAIDs [9,45]. During animal testing in which stomach ulcers were induced by indomethacin, curcumin was responsible for

dose-dependent protection of the gastric mucosa; 60 mg of curcumin per kilogram of body weight was able to prevent 85% of the damage
caused by indomethacin [45]. In a Thai study, 19 of the 25 patients with endoscopically proven peptic ulcers were cured within twelve
weeks through treatment with curcumin (5x 600 mg per day) [44]. Other patients with symptoms of dyspepsia, gastritis and mucous
membrane irritation also benefitted from curcumin supplementation.
Digestion, liver en bile
Curcuma supports digestion and reduces the symptoms of dyspepsia [1,2,9]. A group of 116 test subjects used 4x500 mg of curcuma
powder each day for seven days or a placebo.
Supplementation with curcuma resulted in a significant reduction in symptoms (flatulence, nausea, bloated feeling, acid reflux) [1]. In
Indonesia, curcuma has been used from way back to prevent (cholesterol) gall stones. An experiment involving healthy volunteers shows
that (dose-dependent) curcumin stimulates gall bladder contraction and the release of bile and can be useful as a cholekinetic substance [48].
In twelve test subjects who took 20, 40 or 80 mg of curcumin on an empty stomach, after two hours, the gall bladder volume has reduced
by 30, 50 and 70% respectively, observed using ultrasonography of the gall bladder. Research has also revealed that curcuma boosts the
secretion of bile acids (and bilirubin) and improves the bile composition, on account of which the cholesterol in bile is more likely to
remain in solution and does not settle as quickly [9]. Mice that received a gallstone-promoting food for ten weeks which contained 0.5%
curcumin, had 75% fewer gall stones compared to the control group; additionally, the cholesterol level in the bile dropped significantly [3].
Curcuma and curcumin protect the liver and in animal testing counteracted liver damage by ethanol, ccl4 (tetrachlorocarbon), galactosamine,
paracetamol and aspergillus aflatoxin.
Atherosclerosis
Curcumin inhibits atherosclerosis; this has been proven in animal testing [3,50-52]. This is through the inhibition of lipid peroxidation,
improvement of the vessel endothelial function, inhibition of smooth muscle cell proliferation in the vascular wall and improved
vasodilatation; curcumin reduces the LDL cholesterol and triglyceride level, improves the HDL cholesterol level, inhibits LDL oxidation,
inhibits platelet aggregation, reduces a too-high fibrinogen level and improves the ratio between (unfavourable) apolipoprotein B (apoB) and
(favourable) apoA [3,50-55]. In various human pilot studies, it has been proven that curcumin reduces lipid peroxidation and is good for the
blood lipids and fibrinogen level [3,52,55,56]. Significant effects are already seen upwards of a dose of 20 mg of curcumin per day [52].
During a pilot study, ten healthy adults took 500 mg of curcumin per day for a week; the total cholesterol level dropped (on average) by
12%, the level of serum lipid peroxides by 33%, the HDL level rose by 29% [3].
Asthma
In an animal model for asthma, the effectiveness of curcumin was tested in the sensibilisation phase and in airways symptoms that were
present [57].Orally administered curcumin (20 mg/kg/day) relieved significant ovalbumin-induced (acute) airway narrowing and (late)
hyperreactivity of the airways (for histamine). Curcumin has an inflammation-inhibiting and cramp-reducing activity and inhibits the
IgE-dependent release of inflammatory mediators from mast cells (histamine, leucotrienes).
Alzheimers disease
Alzheimers disease is characterised by peptide aggregation (amyloid beta or a-beta) in the brain, which is associated with plaque formation,
inflammation and oxidative stress. Alzheimers disease is less common in people with a higher intake of antioxidants and (natural)
inflammation inhibitors [12,58]. Various in-vitro and animal studies suggest that curcumin helps in the prevention and treatment of
dementia. A low concentration of curcumin, added to the feed of older mice, inhibits the deposit of a- beta in the brain and counteracts
oxidative stress, inflammation and cognitive deterioration through plaque formation; therefore it deals with both the cause and the
consequence [12,59,60]. Curcumin potentially also aids the breakdown of plaques: curcumin is also responsible for the destabilisation of
coagulated a-beta and is more proficient at this than ibuprofen and naproxen.
In-vivo studies show that peripherally injected curcumin passes the blood-brain barrier and binds to plaques. It is still unclear whether, after
having been taken orally, sufficient quantities of curcumin reach the brain. Meanwhile, (phase 2) clinical studies are underway involving
people with mild to moderate dementia, whereby the effect and tolerability of doses of curcumin between 1 and 4 grams a day are being
examined.
Cataracts
Cataracts can potentially be inhibited by the use of curcumin. Rats received curcumin in their feed for a fourteen-day period (75 mg/kg/day).
Subsequently, in-vitro the eye lens was exposed to a cataract-promoting substance. The eye lenses of animals that had eaten curcumin were
more able to resist cataract formation by lipid peroxidation, partially through the increase in the enzyme glutathione S-transferase in the eye
lens epithelium [61]. Diabetic retinopathy and glaucoma which partially occur through the activation of N-methyl-D-aspartate receptors
(NMDA-receptors) in de retina through short periods of hypoxia, whereby an inflammation process occurs. Curcumin protects the eye
(in-vitro) against excitotoxic cell damage through inhibition of (activated) NMDA receptors without disturbing the normal physiological
function of NMDA receptors [62]. In diabetic rats, curcumin inhibited (0.01% diet) and curcuma (0.5% diet) (dose-dependent) the
development of (diabetic) cataract [63].

CONTRA-INDICATIONS
Curcumin can influence the metabolism of medicines; curcumin can boost the action of blood thinners and is (at high doses) contraindicated
in large gallstones or closing of the biliary tract through gallstone blockage, obstructive icterus, acute gallstone colic and extremely toxic
liver disorders. Use of the extract during pregnancy and lactation are advised against.
SIDE EFFECTS
Doses that are too high can give rise to irritation of the gastric mucosa and have to be avoided by patients with a stomach or intestinal
ulcer. Sometimes, the use of yellow root extracts can increase the frequency of defecation.
REFERENCES
1. WHO Monograph Rhizoma Curcumae Longae. In: WHO monographs on selected medicinal plants, vol 1 Genf 1999;115-124.
2. Blumenthal M, Goldberg A, Brinckmann J. Herbal Medicine, Expanded Commission E monographs. American Botanical Council
2000;379-384. Integrative Medicine Communications, ISBN 0-9670772-1-4.
3. Aggarwal BB, Kumar A, Aggarwal MS, Shishodia S. Curcumin derived from turmeric (Curcuma longa): a spice for all seasons.
In: Preuss H, ed. Phytopharmaceuticals in Cancer Chemoprevention. Boca Raton: CRC Press; 2005:349-387.
http://www.agrawal.org/PDF/Curcumin-Season-Bw1.pdf

4. Chainani-Wu N. Safety and anti-inflammatory activity of curcumin: a component of tumeric (Curcuma longa). J Altern
Complement Med. 2003;9(1):161-8.
5. Joe B, Vijaykumar M, Lokesh BR. Biological properties of curcumin-cellular and molecular mechanisms of action. Crit Rev Food
Sci Nutr. 2004;44(2):97-111.
6. Araujo CC, Leon LL. Biological activities of Curcuma longa L. Mem Inst Oswaldo Cruz. 2001;96(5):723-8.
7. Maheshwari RK, Singh AK, Gaddipati J et al. Multiple biological activities of curcumin: a short review. Life Sci.
2006;78(18):2081-7.
8. Sharma RA, Gesher AJ, Steward WP. Curcumin: the story so far. Eur J Cancer 2005;41(13):1955-1968.
9. Curcuma longa (turmeric). Monograph. Altern Med Rev. 2001;6S:S62-6.
10. Gul N, Mujahid TY, Jehan N et al. Studies on the antibacterial effect of different fractions of Curcuma longa against urinary tract
infection isolates. Pakistan Journal of Biological Sciences 2004;7(12):2055-2060.
11. Ram A, Das M, Ghosh B. Curcumin attenuates allergen-induced airway hyperresponsiveness in sensitized guinea pigs. Biol Pharm
Bull. 2003;26(7):1021-4.
12. Yang F, Lim GP, Begum AN et al. Curcumin inhibits formation of amyloid beta oligomers and fibrils, binds plaques, and reduces
amyloid in vivo. J Biol Chem. 2005;280(7):5892-5901.
13. Dickinson DA, Iles KE, Zhang H et al. Curcumin alters EpRE and AP-1 binding complexes and elevates glutamate-cysteine ligase
gene expression. FASEB J. 2003;17(3):473-5.
14. Iqbal M, Sharma SD, Okazaki Y et al. Dietary supplementation of curcumin enhances antioxidant and phase II metabolizing
enzymes in ddy male mice: possible role in protection against chemical carcinogenesis and toxicity. Pharmacol Toxicol.
2003;92:33-38.
15. Ghoneim AI, Abdel-Naim AB, Khalifa AE et al. Protective effects of curcumin against ischaemia/reperfusion insult in rat
forebrain. Pharmacol Res. 2002;46(3):273-9.
16. Rajakrishnan V, Viswanathan P, Rajasekharan KN et al. Neuroprotective role of curcumin from curcuma longa on ethanol-induced
brain damage. Phytother Res. 1999;13(7):571-4.
17. Ramirez-Bosca A, Soler A, Gutierrez MA et al. Antioxidant Curcuma extracts decrease the blood lipid peroxide levels of human
subjects. Age 1995;18:167-169.
18. Hong J, Bose M, Ju J et al. Modulation of arachidonic acid metabolism by curcumin and related beta-diketone derivatives: effects
on cytosolic phospholipase A(2), cyclooxygenases and 5-lipoxygenase. Carcinogenesis. 2004;25(9):1671-9.
19. Lao CD, Ruffin MT 4th, Normolle D et al. Dose escalation of a curcuminoid formulation. BMC Complement Altern Med.
2006;6:10.
20. Arun N, Nalini N. Efficacy of turmeric on blood sugar and polyol pathway in diabetic albino rats. Plant Foods Hum Nutr.
2002;57(1):41-52
21. Singh S, Aggarwal BB. Activation of transcription factor NF-kappa B is suppressed by curcumin (diferuloylmethane). J Biol
Chem. 1995;270(42):24995-5000.
22. Firestein GS. NF-kappaB: Holy Grail for rheumatoid arthritis? Arthritis Rheum. 2004;50(8):2381-6.
23. Drent M, van den Berg R, Haenen GR et al. NF-kappaB activation in sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis.
2001;18(1):50-6.
24. Haefner B. NF-kappa B: arresting a major culprit in cancer. Drug Discov Today. 2002;7(12):653-63.
25. van den Berg R, Haenen GR, van den Berg H et al. Transcription factor NF-kappaB as a potential biomarker for oxidative stress.
Br J Nutr. 2001;86(S1):S121-7.
26. Giardina C, Hubbard AK. Growing old with nuclear factor-kappaB. Cell Stress Chaperones. 2002;7(2):207-12.
27. Garg A, Aggarwal BB. Nuclear transcription factor-kappaB as a target for cancer drug development. Leukemia. 2002
Jun;16(6):1053-68.
28. Zhang M, Deng CS, Zheng JJ et al. Curcumin regulated shift from Th1 to Th2 in trinitrobenzene sulphonic acid-induced chronic
colitis. Acta Pharmacol Sin. 2006;27(8):1071-7.
29. Tourkina E, Gooz P, Oates JC et al. Curcumin-induced apoptosis in scleroderma lung fibroblasts: role of protein kinase cepsilon.
Am J Respir Cell Mol Biol. 2004;31(1):28-35.
30. Satoskar RR, Shah SJ, Shenoy SG. Evaluation of anti-inflammatory property of curcumin (diferuloyl methane) in patients with
postoperative inflammation. Int J Clin Pharmacol Ther Toxicol. 1986;24(12):651-4.
31. Funk JL, Oyarzo JN, Frye JB et al. Turmeric extracts containing curcuminoids prevent experimental rheumatoid arthritis. J Nat
Prod. 2006;69(3):351-5.
32. Sugimoto K, Hanai H, Tozawa K et al. Curcumin prevents and ameliorates trinitrobenzene sulfonic acid-induced colitis in mice.
Gastroenterology. 2002;123(6):1912-22.
33. Bundy R, Walker AF, Middleton RW et al. Turmeric extract may improve irritable bowel syndrome symptomology in otherwise
healthy adults: a pilot study. J Altern Complement Med. 2004;10(6):1015-8.
34. Xu Y, Ku BS, Yao HY et al. The effects of curcumin on depressive-like behaviors in mice. Eur J Pharmacol. 2005;518(1):40-6.
35. Mazumber A, Raghavan K, Weinstein J et al. Inhibition of human immunodeficiency virus type-1 integrase by curcumin. Biochem
Pharmacol 1995;49:1165-1170.
36. Rasmussen HB, Christensen SB, Kvist LP et al. A simple and efficient separation of the curcumins, the antiprotozoal constituents
of Curcuma longa. Planta Med 2000;66:396-398.
37. Kiuchi F, Goto Y, Sugimoto N et al. Nematocidal activity of Turmeric: synergistic action of curcuminoids. Chem Pharm Bul
1993;41:1640-1643.
38. Perez-Arriaga L, Mendoza-Magana ML, Cortes-Zarate R et al. Cytotoxic effect of curcumin on Giardia lamblia trophozoites. Acta
Trop. 2006;98(2):152-61.
39. Singh R, Chandra R, Bose M et al. Antibacterial activity of Curcuma longa rhizome extract on pathogenic bacteria. Current
Science 2002;83(6):737-740.
40. Kim KJ, Yu HH, Cha JD et al. Antibacterial activity of Curcuma longa L. against methicillin-resistant Staphylococcus aureus.
Phytother Res. 2005;19(7):599-604.
41. Mani H, Sidhu GS, Kumari R et al. Curcumin differentially regulates TGF-beta1, its receptors and nitric oxide synthase during
impaired wound healing. Biofactors. 2002;16(1-2):29-43.
42. Jagetia GC, Rajanikant GK. Curcumin treatment enhances the repair and regeneration of wounds in mice exposed to hemibody
gamma-irradiation. Plast Reconstr Surg. 2005;115(2):515-28.
43. Heng MC, Song MK, Harker J et al. Drug-induced suppression of phosphorylase kinase activity correlates with resolution of
psoriasis as assessed by clinical, histological and immunohistochemical parameters. Br J Dermatol. 2000;143(5):937-49.
44. Prucksunand C, Indrasukhsri B, Leethochawalit M et al. Phase II clinical trial on effect of the long turmeric (Curcuma longa

Linn) on healing of peptic ulcer. Southeast Asian J Trop Med Public Health. 2001;32(1):208-15.
45. Swarnakar S, Ganguly K, Kundu P et al. Curcumin regulates expression and activity of matrix metalloproteinases 9 and 2 during
prevention and healing of indomethacin-induced gastric ulcer. J Biol Chem. 2005;280(10):9409-15.
46. Kim DC, Kim SH, Choi BH et al. Curcuma longa extract protects against gastric ulcers by blocking H2 histamine receptors. Biol
Pharm Bull. 2005;28(12):2220-4.
47. Mahady GB, Pendland SL, Yun G et al. Turmeric (Curcuma longa) and curcumin inhibit the growth of Helicobacter pylori, a
group 1 carcinogen. Anticancer Res. 2002;22(6C):4179-81.
48. Rasyid A, Rahman AR, Jaalam K et al. Effect of different curcumin dosages on human gall bladder. Asia Pac J Clin Nutr.
2002;11(4):314-8.
49. Thapliyal R, Deshpande SS, Maru GB. Effects of turmeric on the activities of benzo(a)pyrene-induced cytochrome P-450 isozymes.
J Environ Pathol Toxicol Oncol. 2001;20(1):59-63.
50. Quiles JL, Mesa MD, Ramirez-Tortosa CL et al. Curcuma longa extract supplementation reduces oxidative stress and attenuates
aortic fatty streak development in rabbits. Arterioscler Thromb Vasc Biol. 2002;22(7):1225-31.
51. Ramirez-Tortosa MC, Mesa MD, Aguilera MC et al. Oral administration of a turmeric extract inhibits LDL oxidation and has
hypocholesterolemic effects in rabbits with experimental atherosclerosis. Atherosclerosis. 1999;147(2):371-8.
52. Ramirez-Bosca A, Soler A, Carrion MA et al. An hydroalcoholic extract of curcuma longa lowers the apo B/apo A ratio.
Implications for atherogenesis prevention. Mech Ageing Dev. 2000;119(1-2):41-7.
53. Zahid Ashraf M, Hussain ME, Fahim M. Antiatherosclerotic effects of dietary supplementations of garlic and turmeric:
Restoration of endothelial function in rats. Life Sci. 2005;77(8):837-57.
54. Naito M, Wu X, Nomura H et al. The protective effects of tetrahydrocurcumin on oxidative stress in cholesterol-fed rabbits. J
Atheroscler Thromb. 2002;9(5):243-50.
55. Miquel J, Bernd A, Sempere JM et al. The curcuma antioxidants: pharmacological effects and prospects for future clinical use. A
review. Arch Gerontol Geriatr. 2002;34(1):37-46.
56. Deshpande U, Joseph L, Manjure S et al. Effects of turmeric extracts on lipid profile in human subjects. Med Sci Res
1997;25:695-698.
57. Ram A, Das M, Ghosh B. Curcumin attenuates allergen-induced airway hyperresponsiveness in sensitized guinea pigs. Biol Pharm
Bull. 2003;26(7):1021-1024.
58. Ringman JM, Frautschy SA, Cole GM et al. A potential role of the curry spice curcumin in Alzheimer's disease. Curr Alzheimer
Res. 2005;2(2):131-6.
59. Baum L, Ng A. Curcumin interaction with copper and iron suggests one possible mechanism of action in Alzheimer's disease
animal models. J Alzheimers Dis. 2004;6(4):367-77.
60. Cole GM, Lim GP, Yang F et al. Prevention of Alzheimer's disease: Omega-3 fatty acid and phenolic anti-oxidant interventions.
Neurobiol Aging. 2005;26(S1):133-6.
61. Awasthi S, Srivatava SK, Piper JT et al. Curcumin protects against 4-hydroxy-2-trans-nonenal-induced cataract formation in rat
lenses. Am J Clin Nutr. 1996;64(5):761-6.
62. Matteucci A, Frank C, Domenici MR et al. Curcumin treatment protects rat retinal neurons against excitotoxicity: effect on
N-methyl-D: -aspartate-induced intracellular Ca(2+) increase. Exp Brain Res. 2005;167(4):641-8.
63. Suryanarayana P, Saraswat M, Mrudula T et al. Curcumin and turmeric delay streptozotocin-induced diabetic cataract in rats.
Invest Ophthalmol Vis Sci. 2005;46(6):2092-9.
64. Chearwae W, Anuchapreeda S, Nandigama K et al. Biochemical mechanism of modulation of human P-glycoprotein (ABCB1) by
curcumin I, II, and III purified from Turmeric powder. Biochem Pharmacol. 2004;68(10):2043-52.
65. Chearwae W, Wu CP, Chu HY et al. Curcuminoids purified from turmeric powder modulate the function of human multidrug
resistance protein 1 (ABCC1). Cancer Chemother Pharmacol. 2006;57(3):376-88.
66. Chearwae W, Shukla S, Limtrakul P et al. Modulation of the function of the multidrug resistance-linked ATP-binding cassette
transporter ABCG2 by the cancer chemopreventive agent curcumin. Mol Cancer Ther. 2006;5(8):1995-2006.
67. Sharma RA, McLelland HR, Hill KA, et al. Pharmacodynamic and pharmacokinetic study of oral Curcuma extract in patients with
colorectal cancer. Clin Cancer Res 2001;7:1894-1900.
68. Sharma RA, Euden SA, Platton SL et al. Phase I clinical trial of oral curcumin: biomarkers of systemic activity and compliance.
Clin Cancer Res. 2004;10(20):6847-54.
69. Garcea G, Berry DP, Jones DJ et al. Consumption of the putative chemopreventive agent curcumin by cancer patients: assessment
of curcumin levels in the colorectum and their pharmacodynamic consequences. Cancer Epidemiol Biomarkers Prev.
2005;14(1):120-5.
70. Shoba G, Joy D, Joseph T et al. Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers.
Planta Med. 1998;64(4):353-6.