Curcumin

Curcumin
Skeletal formula
Enol form
Skeletal formula
Keto form
Ball-and-stick model
Ball-and-stick model
Names
IUPAC name
(1E,6E)-1,7-Bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione
Other names
Diferuloylmethane; curcumin I; C.I. 75300; Natural Yellow 3
Identifiers
458-37-7 YesY
ChEBI CHEBI:3962 YesY
ChEMBL ChEMBL116438 N
ChemSpider 839564 YesY
7000
Jmol 3D model Interactive image
PubChem 969516
UNII IT942ZTH98 YesY
Properties
C21H20O6
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).
N verify (what is YesYN ?)
Infobox references

Curcumin (/ˈkərkjuːmən/) is a bright yellow chemical produced by some plants. It is the principal curcuminoid of turmeric, which is a member of the ginger family (Zingiberaceae). It is sold as an herbal supplement, added to cosmetics, used to flavor food, and as a food coloring.[1] As a food additive, its E number is E100.[2]

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.[3]

Chemically, curcumin is a diarylheptanoid. Turmeric's other two curcuminoids are desmethoxycurcumin and bis-desmethoxycurcumin. 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.[4]

Uses

The most common uses are as a dietary supplement, in cosmetics, as a food coloring, and as flavoring for foods such as turmeric-flavored beverages in Japan.[1]

Curcumin

Annual sales of curcumin have increased since 2012, largely due to a sudden increase in its popularity as a dietary supplement.[1] It is also increasingly popular in skin care products that are being marketed as containing natural ingredients or dyes, especially in Asia.[1] The largest market is in North America, where sales exceeded US$20 million in 2014.[1]

Adverse effects

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,[5] though some subjects reported mild nausea or diarrhea.[6]

Chemistry

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.[7]

Curcumin is used as an indicator for boron.[8] It reacts with boric acid to form a red-color compound, rosocyanine.

Biosynthesis

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.[9] Only a few identified compounds, such as anigorufone and pinosylvin, use cinnamic acid as their starting molecule.[10][11] 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.[9] Therefore, it was concluded the second pathway proposed by Roughly and Whiting was correct.

Curcumin biosynthesis diagram

malonyl-CoA (5)

Biosynthetic pathway of curcumin in Curcuma longa.[9]

Pharmacodynamics

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).[12][13][14] Curcumin also inhibits the arachidonate 5-lipoxygenase enzyme in vitro.[15]

Pharmacokinetics

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.[16] Potential factors that limit the bioavailability of curcumin include insolubility in water (more soluble in alkaline solutions) and poor absorption.[17] Numerous approaches to increase curcumin bioavailability have been explored, including the use of absorption factors (such as piperine), liposomes, nanoparticles or a structural analogue.[17]

Research

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.[5] However, several studies of curcumin efficacy and safety revealed poor absorption and low bioavailability.[16][18]

Data from research on curcumin conducted by Bharat Aggarwal, formerly a researcher at the MD Anderson Cancer Center, was deemed fraudulent and subsequently retracted by the publisher.[19]

References

  1. 1 2 3 4 5 Majeed, Shaheen (28 December 2015). "The State of the Curcumin Market". Natural Products Insider.
  2. ↑ European Commission. "Food Additives". Retrieved 2014-02-15.
  3. ↑ H. Vogel, J. Pelletier, Curcumin-biological and medicinal properties, Journal de Pharmacie. 1815;I:289.
  4. ↑ Manolova, Yana; Deneva, Vera; Antonov, Liudmil; et al. (2014). "The effect of the water on the curcumin tautomerism: A quantitative approach". Spectrochimica Acta 132A (1): 815–820. Bibcode:2014AcSpA.132..815M. doi:10.1016/j.saa.2014.05.096.
  5. 1 2 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.
  6. ↑ Hsu, C. H.; Cheng, A. L. (2007). "Clinical studies with curcumin". Advances in Experimental Medicine and Biology 595: 471–480. doi:10.1007/978-0-387-46401-5_21. ISBN 978-0-387-46400-8. PMID 17569225.
  7. ↑ Miłobȩdzka, J.; v. Kostanecki, St.; Lampe, V. (1910). "Zur Kenntnis des Curcumins". Berichte der deutschen chemischen Gesellschaft 43 (2): 2163–70. doi:10.1002/cber.191004302168.
  8. ↑ "EPA Method 212.3: Boron (Colorimetric, Curcumin)" (PDF).
  9. 1 2 3 Kita, Tomoko; Imai, Shinsuke; Sawada, Hiroshi; et al. (2008). "The Biosynthetic Pathway of Curcuminoid in Turmeric (Curcuma longa) as Revealed by 13C-Labeled Precursors". Bioscience, Biotechnology, and Biochemistry 72 (7): 1789. doi:10.1271/bbb.80075.
  10. ↑ Schmitt, Bettina; Hölscher, Dirk; Schneider, Bernd (2000). "Variability of phenylpropanoid precursors in the biosynthesis of phenylphenalenones in Anigozanthos preissii". Phytochemistry 53 (3): 331–7. doi:10.1016/S0031-9422(99)00544-0. PMID 10703053.
  11. ↑ Gehlert, R.; Schoeppner, A.; Kindl, H. (1990). "Stilbene Synthase from Seedlings of Pinus sylvestris: Purification and Induction in Response to Fungal Infection" (pdf). Molecular Plant-Microbe Interactions 3 (6): 444–449. doi:10.1094/MPMI-3-444.
  12. ↑ Reuter, S; Gupta, SC; Park, B; et al. (May 2011). "Epigenetic changes induced by curcumin and other natural compounds". Genes Nutr 6 (2): 93–108. doi:10.1007/s12263-011-0222-1. PMC 3092901. PMID 21516481. Retrieved 12 June 2015.
    Figure 2
  13. ↑ Vahid, F; Zand, H; Nosrat-Mirshekarlou, E; et al. (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.
  14. ↑ "Curcumin". IUPHAR. IUPHAR/BPS Guide to PHARMACOLOGY. Retrieved 22 May 2015.
  15. ↑ Bishayee, K; Khuda-Bukhsh, AR (September 2013). "5-lipoxygenase antagonist therapy: a new approach towards targeted cancer chemotherapy". Acta Biochim. Biophys. Sin. (Shanghai) 45 (9): 709–719. doi:10.1093/abbs/gmt064. PMID 23752617.
  16. 1 2 Devassy, JG; Nwachukwu, ID; Jones, PJ (March 2015). "Curcumin and cancer: barriers to obtaining a health claim". Nutrition Reviews 73 (3): 155-65. doi:10.1093/nutrit/nuu064. PMID 26024538.
  17. 1 2 Anand, P.; Kunnumakkara, A. B.; Newman, R. A.; Aggarwal, B. B. (2007). "Bioavailability of curcumin: problems and promises". Molecular Pharmaceutics 4 (6): 807–818. doi:10.1021/mp700113r. PMID 17999464.
  18. ↑ "ClinicalTrials.gov: Current clinical trials on curcumin". US National Institutes of Health, Clinical Trial Registry. June 2015.
  19. ↑ Ackerman T (29 February 2012). "M.D. Anderson professor under fraud probe". Houston Chronicle. Retrieved 8 March 2016.

External links

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