Curcumin

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Curcumin
Skeletal formula
Enol form
Skeletal formula
Keto form
Ball-and-stick model
Ball-and-stick model
Identifiers
CAS number 458-37-7 YesY
PubChem 969516
ChemSpider 839564 YesY
UNII IT942ZTH98 YesY
ChEBI CHEBI:3962 YesY
ChEMBL CHEMBL116438 N
Jmol-3D images Image 1
Properties
Molecular formula C21H20O6
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)
 N (verify) (what is: YesY/N?)
Infobox references

Curcumin /ˈkərkjuːmən/ (pronounced "Kur kyoo min")[1] 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.[2]

Curcumin can be used for boron quantification in the curcumin method. It reacts with boric acid to form a red-color compound, rosocyanine.

Curcumin is a bright-yellow color and may be used as a food coloring. As a food additive, its E number is E100.[3]

Curcumin

Chemistry[edit]

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.[4]

Curcumin is used as an indicator for boron.[5]

Biosynthesis[edit]

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.[6] Only a few identified compounds, such as anigorufone and pinosylvin, use cinnamic acid as their start molecule.[7][8] 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.[6] Therefore, it was concluded the second pathway proposed by Roughly and Whiting was correct.

Biosynthetic pathway of curcumin in Curcuma longa.[6]

Preliminary research for potential health effects[edit]

Research has identified curcumin as the agent responsible for most of the biological activity of turmeric.[9]

Laboratory research shows that curcumin is a pleiotropic molecule possibly capable of interacting with molecular targets involved in inflammation.[10] 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.[11][12]

A systematic review of the use of curcumin based supplements for treating diabetic wounds found no significant positive outcome for human use.[13] The effectiveness of curcumin has neither been confirmed in sufficient preliminary research nor been conclusively demonstrated in randomized, placebo-controlled, double-blind clinical trials.[14]

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.[15]

Clinical trials in humans are studying the effect of curcumin on various diseases, including multiple myeloma, pancreatic cancer, myelodysplastic syndromes, colon cancer, psoriasis, arthritis, and Alzheimer's disease.[16][17][18][19] 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.[20]

Curcumin has also been shown to be a vitamin D receptor ligand "with implications for colon cancer chemoprevention." [21]

Bioavailability[edit]

In Phase I clinical trials, dietary curcumin was shown to exhibit poor bioavailability (i.e., low levels in plasma and tissues).[22] 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.[22]

The bioavailability of curcumin ingested in foods may be increased as a result of cooking or dissolution in oil.[23]

Resistance[edit]

Overexpression of the ATP-binding cassette gene ABCA1 has been reported to confer resistance to curcumin in terms of NFkappaB activation that can be reversed by ABCA1 silencing.[24]

Potential risks and side-effects[edit]

Kawanishi et al. remarked that curcumin, like many antioxidants, can be a "double-edge sword," whereby, in the test tube, carcinogenic and pro-oxidant effects may be seen in addition to anticancer and antioxidant effects.[25] Carcinogenic effects are inferred from interference with the p53 tumor suppressor pathway, an important factor in human colon cancer.[26] In vitro and in vivo studies suggest that curcumin can have carcinogenic effects.[27][28][29]

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.[30] More recently, curcumin was found to alter iron metabolism by chelating iron and suppressing the protein hepcidin, potentially causing iron deficiency in susceptible patients.[31] Further studies seem to be necessary to establish the benefit/risk profile of curcumin.[27]

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.[32] Curcumin has embryotoxic and teratogenic effects on zebrafishes (Danio rerio) embryos.[33]

References[edit]

Notes
  1. ^ Dorland (2011-06-09). Dorland's Illustrated Medical Dictionary, 32nd Edition. ISBN 1455709859. Retrieved May 19, 2013.  Published 2011.
  2. ^ Kolev, Tsonko M.; Velcheva, Evelina A.; Stamboliyska, Bistra A.; Spiteller, Michael (2005). "DFT and experimental studies of the structure and vibrational spectra of curcumin". International Journal of Quantum Chemistry 102 (6): 1069–79. doi:10.1002/qua.20469. 
  3. ^ European Commission. "Food Additives". Retrieved 2014-02-15. 
  4. ^ 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. 
  5. ^ "EPA Method 212.3: Boron (Colorimetric, Curcumin)". 
  6. ^ a b c Kita, Tomoko; Imai, Shinsuke; Sawada, Hiroshi; Kumagai, Hidehiko; Seto, Haruo (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. 
  7. ^ 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. 
  8. ^ 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. 
  9. ^ Aggarwal, Bharat B.; Sundaram, Chitra; Malani, Nikita; Ichikawa, Haruyo (2007). "Curcumin: the Indian solid gold". Advances in Experimental Medicine and Biology. Advan Exp Med Biol 595: 1–75. doi:10.1007/978-0-387-46401-5_1. ISBN 978-0-387-46400-8. PMID 17569205. 
  10. ^ Gupta SC et al. (2011). "Multitargeting by curcumin as revealed by molecular interaction studies". Nat Prod Rep 28 (12): 1937–55. doi:10.1039/c1np00051a. PMC 3604998. PMID 21979811. 
  11. ^ Abe Y, Hashimoto S, Horie T (1999). "Curcumin inhibition of inflammatory cytokine production by human peripheral blood monocytes and alveolar macrophages". Pharmacol Res 39 (1): 41–7. doi:10.1006/phrs.1998.0404. PMID 10051376. 
  12. ^ Goel A, Kunnumakkara AB, Aggarwal BB (2008). "Curcumin as "Curecumin": from kitchen to clinic". Biochem Pharmacol 75 (4): 787–809. doi:10.1016/j.bcp.2007.08.016. PMID 17900536. 
  13. ^ Maier, HM; Ilich, JZ; Kim, JS; Spicer, MT (2013). "Nutrition supplementation for diabetic wound healing: A systematic review of current literature". Skinmed 11 (4): 217–24; quiz 224–5. PMID 24053007. 
  14. ^ Mancuso, C.; Barone, E. (2009). "Curcumin in clinical practice: myth or reality?". Trends in Pharmacological Science 30 (7): 333–334. doi:10.1016/j.tips.2009.04.004. PMID 19523696. 
  15. ^ 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." 
  16. ^ Hatcher, H.; Planalp, R.; Cho, J.; Torti, F. M.; Torti, S. V. (2008). "Curcumin: From ancient medicine to current clinical trials". Cellular and Molecular Life Sciences 65 (11): 1631–52. doi:10.1007/s00018-008-7452-4. PMID 18324353. 
  17. ^ Yan, Jiao; Wilkinson, Di, Wang, Hatcher, Kock, D'Agostino, Jr, Knovich, Torti, Torti corresponding author (8 January 2009). "Red Cells, Iron, and Erythropoiesis Curcumin, a cancer chemopreventive and chemotherapeutic agent, is a biologically active iron chelator". Blood. 113(2): (Prepublished online 2008 September 24.): 462–469. doi:10.1182/blood-2008-05-155952. PMC 2615657. PMID 18815282. 
  18. ^ "ClinicalTrials.gov: Current clinical trials on curcumin". US National Institutes of Health, Clinical Trial Registry. 2013. 
  19. ^ Zhao, LN.; Chiu, SW.; Benoit, J.; Chew, LY.; Mu, Y. (Jun 2012). "The effect of curcumin on the stability of Aβ dimers". J Phys Chem B 116 (25): 7428–35. doi:10.1021/jp3034209. PMID 22690789. 
  20. ^ Shehzad A et al. (2010). "Curcumin therapeutic promises and bioavailability in colorectal cancer". Drugs of Today 46 (7): 523–32. doi:10.1358/dot.2010.46.7.1509560. PMID 20683505. 
  21. ^ Bartik, L; Whitfield, GK; Kaczmarska, M; Lowmiller, CL; Moffet, EW; Furmick, JK; Hernandez, Z; Haussler, CA; Haussler, MR; Jurutka, PW (2010). "Curcumin: A novel nutritionally derived ligand of the vitamin D receptor with implications for colon cancer chemoprevention". The Journal of nutritional biochemistry 21 (12): 1153–61. doi:10.1016/j.jnutbio.2009.09.012. PMC 2891903. PMID 20153625. 
  22. ^ a b 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. 
  23. ^ Marczylo, T. H.; Verschoyle, R. D.; Cooke, D. N.; Morazzoni, P.; Steward, W. P.; Gescher, A. J. (2007). "Comparison of systemic availability of curcumin with that of curcumin formulated with phosphatidylcholine". Cancer Chemotherapy and Pharmacology 60 (2): 171–177. doi:10.1007/s00280-006-0355-x. PMID 17051370. 
  24. ^ Bachmeier BE, Iancu CM, Killian PH, Kronski E, Mirisola V, Angelini G, et al. (2009). "Overexpression of the ATP binding cassette gene ABCA1 determines resistance to Curcumin in M14 melanoma cells". Mol Cancer 8: 129–141. doi:10.1186/1476-4598-8-129. PMC 2804606. PMID 20030852. 
  25. ^ Kawanishi, S.; Oikawa, S.; Murata, M. (2005). "Evaluation for safety of antioxidant chemopreventive agents". Antioxidants & Redox Signaling 7 (11–12): 1728–1739. doi:10.1089/ars.2005.7.1728. PMID 16356133. 
  26. ^ Moos, P. J.; Edes, K.; Mullally, J. E.; Fitzpatrick, F. A. (2004). "Curcumin impairs tumor suppressor p53 function in colon cancer cells". Carcinogenesis 25 (9): 1611–1617. doi:10.1093/carcin/bgh163. PMID 15090465. 
  27. ^ a b Burgos-Moron, E.; Calderón-Montaño, J. M.; Salvador, J.; Robles, A.; López-Lázaro, M. (2010). "The dark side of curcumin" (pdf). International Journal of Cancer 126 (7): 1771–1775. doi:10.1002/ijc.24967. PMID 19830693. 
  28. ^ Dance-Barnes, S. T.; Kock, N. D.; Moore, J. E.; Lin, E. Y.; Mosley, L. J., et al. (2009). "Lung tumor promotion by curcumin". Carcinogenesis 30 (6): 1016–1023. doi:10.1093/carcin/bgp082. PMC 2691137. PMID 19359593. 
  29. ^ López-Lázaro, M.; Kock, N. D.; Moore, J. E.; Lin, E. Y.; Mosley, L. J., et al. (2008). "Anticancer and carcinogenic properties of curcumin: considerations for its clinical development as a cancer chemopreventive and chemotherapeutic agent". Molecular Nutrition and Food Research 52 (Supplement 1): S103–S127. doi:10.1002/mnfr.200700238. PMID 18496811. 
  30. ^ Hsu, C. H.; Cheng, A. L. (2007). "Clinical studies with curcumin". Advances in Experimental Medicine and Biology. 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. 
  31. ^ Jiao, Y.; Wilkinson, J.; Di, X.; Wang, W.; Hatcher, H., et al. (January 2009). "Curcumin, a cancer chemopreventive and chemotherapeutic agent, is a biologically active iron chelator". Blood 113 (2): 462–469. doi:10.1182/blood-2008-05-155952. PMC 2615657. PMID 18815282. 
  32. ^ Vijayalaxmi (1980). "Genetic effects of turmeric and curcumin in mice and rats". Mutation Research 79 (2): 125–132. doi:10.1016/0165-1218(80)90080-4. PMID 7432370. 
  33. ^ Wu, J. Y.; Lin, C. Y.; Lin, T. W.; Ken, C. F.; Wen, Y. D. (2007). "Curcumin Affects Development of Zebrafish Embryo". Biol. Pharm. Bull 30 (7): 1336–1339. doi:10.1248/bpb.30.1336. PMID 17603177. 

See also: Esatbeyoglu, Tuba; Huebbe, Patricia; Ernst, Insa M. A.; Chin, Dawn, et al.; Wagner, Anika E.; Rimbach, Gerald (2012). "Curcumin-From Molecule to Biological Function". Angewandte Chemie International Edition 51 (22): 5308. doi:10.1002/anie.201107724. 

External links[edit]