|This article relies too much on references to primary sources. (June 2015)|
Diferuloylmethane; curcumin I; C.I. 75300; Natural Yellow 3
|Jmol interactive 3D||Image|
|Molar mass||368.39 g·mol−1|
|Appearance||Bright yellow-orange powder|
|Melting point||183 °C (361 °F; 456 K)|
Except where otherwise noted, data are 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). It was first discovered about two centuries ago when Vogel and Pelletier reported the isolation of a “yellow coloring-matter” from the rhizomes of Curcuma longa (turmeric) and named it curcumin. 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 organic solvents, while in water the 1,3-diketo dominates.
Two preliminary clinical studies in cancer patients consuming high doses of curcumin (up to 8 grams per day for 3-4 months) showed no toxicity, with some subjects reporting mild nausea or diarrhea.
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 starting 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.
In vitro, curcumin has been shown to inhibit certain epigenetic enzymes (the histone deacetylases: HDAC1, HDAC3, and HDAC8) and transcriptional co-activator proteins (the p300 histone acetyltransferase). Curcumin also inhibits the arachidonate 5-lipoxygenase enzyme in vitro, as well as the enzyme cyclooxygenase.
In Phase I clinical trials, dietary curcumin was shown to exhibit poor bioavailability, exhibited by rapid metabolism, low levels in plasma and tissues, and extensive rapid excretion. Potential factors that limit the bioavailability of curcumin include insolubility in water (more soluble in alkaline solutions) and poor absorption. Numerous approaches to increase curcumin bioavailability have been explored, including the use of absorption factors (such as piperine), liposomes, nanoparticles or a structural analogue.
A survey of the literature shows a number of potential effects under study and that daily consumption 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.
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This review summarizes current knowledge about the effect of curcumin on the regulation of histone deacetylases, histone acetyltransferases, DNA methyltransferase I, and miRNAs. ... Because of the differing effect of curcumin on the different subtypes of HDAC enzymes, further research is required to understand the mechanism of curcumin on HDAC expression. ... Thus, curcumin’s ability to suppress p300/CBP HAT activity may be responsible, at least in part, for its potent NF-κB inhibitory activity.
- Vahid F, Zand H, Nosrat-Mirshekarlou E, Najafi R, Hekmatdoost A (May 2015). "The role dietary of bioactive compounds on the regulation of histone acetylases and deacetylases: a review". Gene 562 (1): 8–15. doi:10.1016/j.gene.2015.02.045. PMID 25701602.
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- Goel, Ajay; Kunnumakkara, Ajaikumar B.; Aggarwal, Bharat B. (2008). "Curcumin as "Curecumin": From kitchen to clinic". Biochemical Pharmacology 75 (4): 787–809. doi:10.1016/j.bcp.2007.08.016. PMID 17900536.
Pilot phase I clinical trials have shown curcumin to be safe even when consumed at a daily dose of 12g for 3 months.
- "ClinicalTrials.gov: Current clinical trials on curcumin". US National Institutes of Health, Clinical Trial Registry. June 2015.
- 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