|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|
|Melting point||183 °C (361 °F; 456 K)|
|Except where noted otherwise, data are given for materials in their standard state (at 25 °C (77 °F), 100 kPa)|
|(what is: / ?)|
Curcumin // (pronounced "Kur kyoo min") is a diarylheptanoid. It 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 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
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.
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 been 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.
Clinical trials in humans are studying the effect of curcumin on various diseases, including multiple myeloma, pancreatic cancer, myelodysplastic syndromes, colon cancer, psoriasis, arthritis, major depressive disorder and Alzheimer's disease. A number of trials studying curcumin efficacy and safety revealed poor absorption and low bioavailability. Methods to possibly increase absorption and systemic bioavailability are under study, including combined administration with piperine and quercetin.
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 insolubility in water (more soluble in alkaline solutions), poor absorption, rapid metabolism and systemic elimination. Numerous approaches to increasing curcumin bioavailability have been explored, including the use of absorption factors such as piperine. Because of its stability and physical properties, pure curcumin can be vaporized or smoked, obviating the need for oral absorption factors. This ROA however carries higher risk of chelating iron from hemoglobin, and potentially higher risk of carcinogenicity.
The bioavailability of curcumin ingested in foods may be increased as a result of cooking or dissolution in oil.
Potential risks and side-effects
Curcumin and turmeric are considered safe under conventional daily consumption amounts for most adults.
Effects of curcumin may be interpreted as a "double-edge sword," whereby, in vitro, 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 that curcumin is either safe or unsafe for pregnant women. However, there is still some concern that 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 (either positive or negative) on the pregnancy rate or number of live or dead embryos. Curcumin has embryotoxic and teratogenic effects on zebrafish (Danio rerio) embryos.
Possible diagnostic use
Preliminary research has found that curcuminoid binds to amyloid proteins associated with Alzheimer's disease. Because curcumin increases fluorescent activity after it binds to amyloid protein, curcumin is being studied as a possible identifier. Tests have detected amyloid proteins in human eyes, offering the possibility that simple eye exams could provide early detection of the disease.
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