|This article relies too much on references to primary sources. (December 2011)|
Diferuloylmethane; curcumin I; C.I. 75300; Natural Yellow 3
|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 is given for materials in their standard state (at 25 °C (77 °F), 100 kPa)
|what is: / ?)(|
Curcumin (//) is a diarylheptanoid. It is the principal curcuminoid of 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.
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.
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.
^ Malonyl-CoA should be labeled 5.
A survey of the literature shows a number of potential effects under study and that daily doses over a 3-month period of up to 12 grams were safe. However, several studies of curcumin efficacy and safety revealed poor absorption and low bioavailability.
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.
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.[medical citation needed]
Curcumin's pharmacodynamic targets include epigenetic enzymes and transcriptional co-activator proteins (both histone deacetylases and the p300 histone acetylase) and arachidonate 5-lipoxygenase, among others.
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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Pilot phase I clinical trials have shown curcumin to be safe even when consumed at a daily dose of 12g for 3 months.
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