|This article relies on references to primary sources. (December 2011)|
|Jmol-3D images||Image 1|
|Molar mass||368.38 g mol−1|
|Appearance||Bright yellow-orange powder|
183 °C, 456 K, 361 °F
| (what is: / ?)
Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Curcumin (pronounced "Kur kyoo min") is the principal curcuminoid of the popular South Asian spice turmeric, which is a member of the ginger family (Zingiberaceae). Turmeric's other two curcuminoids are desmethoxycurcumin and bis-desmethoxycurcumin. The curcuminoids are natural phenols that are responsible for the yellow color of turmeric. Curcumin can exist in several tautomeric forms, including a 1,3-diketo form and two equivalent enol forms. The enol form is more energetically stable in the solid phase and in solution.
Curcumin incorporates several functional groups. The aromatic ring systems, which are phenols, are connected by two α,β-unsaturated carbonyl groups. The diketones form stable enols and are readily deprotonated to form enolates; the α,β-unsaturated carbonyl group is a good Michael acceptor and undergoes nucleophilic addition. The structure was first identified in 1910 by J. Miłobędzka, Stanisław Kostanecki and Wiktor Lampe.
The biosynthetic route of curcumin has proven to be very difficult for researchers to determine. In 1973 Roughly and Whiting proposed two mechanisms for curcumin biosynthesis. The first mechanism involved a chain extension reaction by cinnamic acid and 5 malonyl-CoA molecules that eventually arylized into a curcuminoid. The second mechanism involved two cinnamate units being coupled together by malonyl-CoA. Both mechanisms use cinnamic acid as their starting point, which is derived from the amino acid phenylalanine. This is noteworthy because plant biosyntheses employing cinnamic acid as a starting point are rare compared to the more common use of p-coumaric acid. Only a few identified compounds, such as anigorufone and pinosylvin, use cinnamic acid as their start molecule. An experimentally backed route was not presented until 2008. This proposed biosynthetic route follows both the first and second mechanisms suggested by Roughley and Whiting. However, the labeling data supported the first mechanism model in which 5 malonyl-CoA molecules react with cinnamic acid to form curcumin. However, the sequencing in which the functional groups, the alcohol and the methoxy, introduce themselves onto the curcuminoid seems to support more strongly the second proposed mechanism. Therefore, it was concluded the second pathway proposed by Roughly and Whiting was correct.
Preliminary research for potential health effects
A systematic review of the use of curcumin based supplements for treating diabetic wounds found no significant positive outcome for human use. The effectiveness of curcumin has neither been confirmed in sufficient preliminary research, nor conclusively demonstrated in randomized, placebo-controlled, double-blind clinical trials.
A survey of the literature shows a number of other potential uses and that daily doses over a 3-month period of up to 12 grams proved safe.
Research in the latter half of the 20th century identified curcumin as the agent responsible for most of the biological activity of turmeric.
As of 2008, clinical trials in humans were underway, studying the effect of curcumin on various diseases, including multiple myeloma, pancreatic cancer, myelodysplastic syndromes, colon cancer, psoriasis, and Alzheimer's disease.
Laboratory research shows that curcumin is a pleiotropic molecule possibly capable of interacting with molecular targets involved in inflammation. In vitro, curcumin modulates the inflammatory response by down-regulating the activity of cyclooxygenase-2, lipoxygenase, and inducible nitric oxide synthase enzymes; and inhibits several other enzymes involved in inflammation mechanisms.
In Phase I clinical trials, dietary curcumin was shown to exhibit poor bioavailability (i.e., low levels in plasma and tissues). Potential factors that limit the bioavailability of curcumin include poor absorption, rapid metabolism, and rapid systemic elimination. Numerous approaches to increasing curcumin bioavailability have been explored, including the use of adjuvants like piperine.
The bioavailability of curcumin ingested in foods may be increased as a result of cooking or dissolution in oil.
Potential risks and side effects
Kawanishi et al. remarked that curcumin, like many antioxidants, can be a "double-edged sword" where, in the test tube, carcinogenic and pro-oxidant effects may be seen in addition to anticancer and antioxidant effects. Carcinogenic effects are inferred from interference with the p53 tumor suppressor pathway, an important factor in human colon cancer. In vitro and in vivo studies suggest that curcumin can have carcinogenic effects.
Clinical studies in humans with high doses (2–12 grams) of curcumin have shown few side effects, with some subjects reporting mild nausea or diarrhea. More recently, curcumin was found to alter iron metabolism by chelating iron and suppressing the protein hepcidin, potentially causing iron deficiency in susceptible patients. Further studies seem to be necessary to establish the benefit/risk profile of curcumin.
There is no or little evidence to suggest curcumin is either safe or unsafe for pregnant women. However, there is still some concern medicinal use of products containing curcumin could stimulate the uterus, which may lead to a miscarriage, although there is not much evidence to support this claim. According to experiments done on rats and guinea pigs, there is no obvious effect (neither positive, nor negative) on the pregnancy rate or number of live or dead embryos. Curcumin has embryotoxic and teratogenic effects on zebrafishes (Danio rerio) embryos.
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See also: Esatbeyoglu, Tuba; Huebbe, Patricia; Ernst, Insa M. A.; Chin, Dawn, et al. (2012). "Curcumin-From Molecule to Biological Function". Angewandte Chemie International Edition 51 (22): 5308. doi:10.1002/anie.201107724.
- Turmeric and curcumin, from Memorial Sloan-Kettering Cancer Center
- Turmeric and curcumin, from M.D. Anderson Cancer Center
- Turmeric, from the University of Maryland Medical Center