Turmeric, Curcumin (Curcuma longa)
Synonyms / Common Names / Related Terms
Amomoum curcuma, anlatone (constituent), ar-tumerone, CUR, Curcuma, Curcuma aromatica, Curcuma aromatica Salisbury, Curcuma domestica, Curcuma domestica Valet, Curcuma longa, Curcuma longa Linn., Curcuma longa rhizoma, curcuma oil, curcumin, diferuloylmethane, E zhu, Gelbwurzel, gurkemeje, Haldi, Haridra, Indian saffron, Indian yellow root, Jiang huang, kunir, kunyit, Kurkumawurzelstock, Kyoo, Number Ten (NT), Olena, Radix zedoaria longa, Rhizome de curcuma, safran des Indes, sesquiterpenoids, shati, tumeric, turmeric oil, turmeric root, tumerone (constituent), Ukon, yellowroot, Zedoary, Zingiberaceae (family), zingiberene, Zitterwurzel.
Mechanism of Action
- Constituents: Curcumin (diferuloylmethane), a polyphenol compound responsible for the bright yellow color of turmeric, is believed to be the principal pharmacological agent. It is prepared from the roots of Curcuma longa.66 In addition to curcumin, turmeric contains the curcuminoids atlantone, bisdemethoxycurcumin, demethoxycurcumin, diaryl heptanoids, and tumerone. Turmeric also contains sesquiterpenoids7 and the constituent ar-tumerone67. Other constituents include sugars, resins, proteins, vitamins, and minerals (including iron and potassium).
- Alzheimer's effects: Beta-Amyloid (betaA)-induced oxidative stress is a well-established pathway of neuronal cell death in Alzheimer's disease.2 Three curcuminoids from turmeric (Curcuma longa L.), including curcumin, demethoxycurcumin, and bisdemethoxycurcumin, were found to protect PC12 rat pheochromocytoma and normal human umbilical vein endothelial (HUVEC) cells from betaA(1-42) insult. These compounds may protect the cells from betaA(1-42) insult through antioxidant pathways. Other animal studies of Alzheimer's disease also suggest that curcumin may reduce levels of amyloid and oxidized proteins and prevent cognitive deficits.1 One alternative mechanism of action for these effects suggested by Baum et al. is metal chelation, which may reduce amyloid aggregation or oxidative neurotoxicity. Since curcumin more readily binds the redox-active metals and than the redox-inactive , curcumin might exert a net protective effect against beta toxicity or might suppress inflammatory damage by preventing metal induction of NF-kappaB. Mouse studies that evaluated the effects of dietary curcumin on inflammation, oxidative damage, and plaque pathology demonstrated that both low and high doses of curcumin significantly lowered oxidized proteins and interleukin-1beta, which is a proinflammatory cytokine elevated in the brains of these mice.3 Low-dose but not high-dose curcumin treatment has been shown to reduce the astrocytic marker GFAP and significantly decrease insoluble beta-amyloid (Abeta), soluble Abeta, and plaque burden by 43-50%. However, levels of amyloid precursor (APP) in the membrane fraction were not reduced.
- Antibacterial effects: The ethyl acetate extract of Curcuma longa L. has demonstrated a higher antibacterial activity than the methanol extract or water extract.4
- Anti-inflammatory effects: Turmeric has been associated with the inhibition of tumor necrosis factor-α, interleukin-8, monocyte inflammatory protein-1, interleukin-1B, and monocyte chemotactic protein-1 25. Turmeric and its constituent curcumin have been found to inhibit lipoxygenase and cyclooxygenase in rat tissues and in vitro23,18,22, as well as thromboxane B219 and leukotriene B4 formation28,23. Based on animal study, oral administration of curcumin may reduce expression of several cytokines, chemokines, and proteinases known to mediate aneurismal degeneration.36 In rat macrophages, curcumin inhibits the incorporation of arachidonic acid into membrane lipids, as well as prostaglandin E2, leukotriene B4, and leukotriene C4, but does not affect the release of arachidonic acid.30 Curcumin also inhibits the secretion of collagenase, elastase, and hyaluronidase. Inhibition of neutrophil function has been noted24, and in vitro research demonstrates that curcumin inhibits 5-hydroxy-eicosatetraenoic acid (5-HETE) in intact human neutrophils.18 Turmeric has been found to block cytokine-induced transcription of leukocyte adhesion molecules ICAM-1, VCAM-1, and E-selectin29, and it appears to induce the production of endogenous TGF-B1 in animal wounds33. Curcumin down-regulates transcription of genes responsible for the production of chemotactic cytokines in bone marrow stromal cells.35 Curcumin reduces chemically-induced rat paw edema32,31 and liver inflammation34.
- Antioxidant effects: Turmeric has been reported to possess antioxidant properties in vitro and in animal studies.59,60,61,62,63,11,64,65,35 Turmeric preparations have been found to scavenge free radicals (peroxides) and phenolic oxidants29, inhibit lipid peroxidation induced by chemical agents68,69, and inhibit iron-dependent lipid peroxidation in rat tissues.70,71 In vitro research shows that turmeric may prevent oxidative damage to DNA72 and may be a potent scavenger of nitric acid65. Curcumin appears to generate a hydroxyl radical73. Structural features of curcuminoids that may contribute to antioxidant activity include phenolic and methoxy groups on phenyl rings and diketones.74 Research using aqueous extracts of turmeric suggests that curcumin is not the only antioxidant in turmeric 75, and turmerin has been identified as a water-soluble peptide from turmeric with antioxidant properties 76. Animal studies have reported the reversal of hepatonecrosis and fatty changes associated with turmeric, with reversal of aflatoxin-induced liver damage 8.
- Anti-platelet aggregation effects: Curcumin inhibits thromboxane A2 without affecting the synthesis of prostaglandin I220 In vitro, curcumin inhibits platelet aggregation induced by ADP, epinephrine, or collagen.21,19 Turmeric appears to inhibit arachidonic acid incorporation into platelet phospholipids, degradation of phospholipids, and cyclooxygenase.77,9
- Anti-proliferative effects: Multiple pre-clinical studies have explored potential anti-cancer mechanisms of curcumin.37,39,40,41,42,43,44,45,46,5,47,48,49,6,15,12,51,52,53,54,55,56 In a rat model, the effects of 0.2% or 0.6% dietary curcumin were evaluated on chemically induced colon adenocarcinoma.50 Histological examination after one year revealed both preventative and therapeutic benefits of curcumin when compared to animals not receiving curcumin, with better response at higher doses. Histologic examination revealed evidence of apoptosis of cancer cells. In mice, six weeks of a 2% curcumin diet was found to decrease cellular proliferation and increase apoptosis of implanted androgen-dependent LNCaP prostate cancer cells.45 However, in vitro research on the anti-proliferative effects of curcumin on breast cancer cells reported no evidence of apoptosis.78 Dietary turmeric extract given to mice (2% or 5% of diet) significantly inhibited chemically-induced skin and gastric tumors.38 A 57% reduction in the incidence of chemically-induced colonic epithelial cell dysplasia was noted in mice fed a 2% curcumin diet.79 Curcumin has been found to inhibit the formation of chemically-induced aberrant crypt foci in rat colons, and to inhibit colonic mucosal tyrosine protein kinase activity.22 In vitro, curcumin derivatives demonstrated anti-tumor effects against leukemic cells, and in test animals, they decreased the incidence of experimentally-induced forestomach tumors by 20% and the number of skin tumors and papillomas by 68% and 57%, respectively.52 HL-60 leukemia cells are susceptible to curcumin treatment in vitro.80 Curcumin may suppress telomerase activity and induce apoptosis in human cancer cell lines.40 Extracts of turmeric and curcumin have been found to be to be non-mutagenic using the Ames test and to serve protective roles against experimental mutagenesis induced by capsaicin, chili extract, and tobacco-derived mutagens.14 In a different animal study, however, concentrations up to 5mM curcumin did not protect against cytotoxicity of paracetamol in freshly isolated hepatocytes, and curcumin itself was found to be mildly hepatotoxic at high doses.13 Curcumin inhibits the growth of human epidermoid carcinoma A431 cells in vitro.81 Topical application of curcumin inhibits chemically-induced tumor promotion in mouse skin82, which may be attributable to suppression of protein kinase C activity83. Curcumins have also been noted in vitro to inhibit the nitrosation of methyl urea by sodium nitrate.84 In vitro research suggests that curcumin exerts activity against human breast cancer cells56, including hormone-dependent, hormone-independent, and multidrug-resistant cell lines78, which may occur via effects on aryl hydrocarbon receptors57 or ornithine decarboxylase activity78. The protective role of curcumin against carcinogenesis has also been attributed to antioxidant effects.72 In rats, curcumin is reported to be protective against radiation-induced lung fibrosis and micronuclei formation85 and to protect against acute adriamycin-induced myocardial toxicity 58. In rat aortic smooth muscle cells, curcumin inhibited cell proliferation, arrested cell cycle progression, and induced cell apoptosis.86 In vitro, curcumin has exhibited activity against human B-cells immortalized by Epstein-Barr virus.87 Anti-angiogenic properties have been proposed.88,89,45,90
- Lipid-lowering effects: In rat models of hyperlipidemia, a diet of 0.5% curcumin for eight weeks significantly lowered serum low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), total cholesterol, and triglyceride levels, possibly by enhancing the activity of hepatic cholesterol-7a-hydroxylase and increasing cholesterol catabolism.91,17,16 The turmeric constituents demethoxycurcumin, bisdemethoxycurcumin, and acetylcurcumin appear to inhibit -stimulated lipid peroxidation in rat tissues and liver microsomes.69 In a rat model of hyperlipidemia, a 50% ethanolic extract of turmeric was associated with a significant reduction in the ratio of total cholesterol to phospholipids.92 In rabbits fed a high cholesterol diet, oral turmeric (1.6-3.2mg/kg) was associated with lower levels of plasma cholesterol and triglycerides than a control group, although no differences in atherogenesis were noted on histological examination of aortas.93 Cholesterol levels were lower in the 1.6mg/kg group.
- Gastro-protective effects: Oral administration of turmeric to rats (500mg/kg) significantly reduces the incidence of chemically-induced duodenal ulcers and is associated with an increase in intestinal wall mucus and non-protein sulfhydryl content.26 However, early research in guinea pigs reported that various constituents of turmeric do not protect against histamine-induced gastric ulcerations.94
- Gallbladder effects: Gallbladder contraction over the two-hour period following the administration of 20mg curcumin has been demonstrated in humans.10 Animal research reports that curcumin in the diet reduces the incidence of chemically-induced gallstones in mice.95
- Hypoglycemic effects: Based on animal study, both curcuminoids and sesquiterpenoids in turmeric may exhibit hypoglycemic effects via PPAR-gamma activation.7
- Weight loss effects: In a rat study that investigated a Chinese herbal formulation called Number Ten for weight loss, leptin and body fat decreased significantly in the treatment group compared to the control group (p<0.009 and p<0.006, respectively).
- Other effects: Chelation: In vitro research on liposomal membranes has demonstrated that curcumin forms chelates with iron.96,97 Phototoxicity: Curcumin in low concentrations has been found to potentiate phototoxicity to the bacteria S. typhimurium and E. coli.98
- Absorption: Animal research shows that the absorption of curcumin after oral administration varies from 25-60%, with most of the absorbed flavonoid being metabolized in the intestinal mucosa and liver.99 The remainder is excreted in the feces.100
- Distribution: Based on a clinical trial, Garcea et al. report that a daily dose of 3.6g curcumin may achieve pharmacologically efficacious levels in the colorectum with negligible distribution of curcumin outside the gut.5
- Bioavailability: Authors of one clinical trial concluded that the lack of quantifiable curcumin in the plasma observed after a dose as high as 3,600mg is consistent with recent clinical reports, in which oral doses of 30-180mg curcumin failed to establish detectable plasma levels, and doses of 4,000-12,000mg yielded curcumin peak levels of 0.5-2mcM/L after one hour of administration.5 The authors also concluded that products of metabolic curcumin conjugation are present in the colorectum of humans who have ingested curcumin, but that these metabolites only contribute to a very minor extent of the overall colorectal load of curcumin-derived species. This finding is consistent with the idea that the pharmacologic effects of curcumin in the colorectum are probably caused by the parent compound and not by its metabolites.5
- Pharmacodynamics: In rats, curcumin is reported to be a potent inhibitor of cytochrome P450 (CYP) 1A1/1A2, a less potent inhibitor of CYP 2B1/2B2, and a weak inhibitor of CYP 2E1.27 Inhibition of cytochrome P450 has also been demonstrated in vitro .52 Turmeric may decrease hepatocyte glutathione levels101; curcumin appears to induce glutathion-s-transferase activity in mice102.
- Curcumin, a constituent of turmeric, completely inhibited mycelial growth of Aspergillus alliaceus isolate 791 at 0.1% (w/v) and decreased ochratoxin A production by approximately 70% at 0.01% (w/v) .103
- In the checkerboard test, the ethyl acetate extract of Curcuma longa L. markedly lowered the MICs of ampicillin and oxacillin against methicillin-resistant Staphylococcus aureus (MRSA).4 In the bacterial invasion assay, MRSA intracellular invasion was significantly decreased in the presence of 0.125-2mg/mL of Curcuma longa extract compared to the control group.
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- Kim, K. J., Yu, H. H., Cha, J. D., Seo, S. J., Choi, N. Y., and You, Y. O. Antibacterial activity of Curcuma longa L. against methicillin-resistant Staphylococcus aureus. Phytother Res 2005;19(7):599-604. 16161063
- Garcea, G., Berry, D. P., Jones, D. J., Singh, R., Dennison, A. R., Farmer, P. B., Sharma, R. A., Steward, W. P., and Gescher, A. J. 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):120-125. 15668484
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