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{{Short description|Principal curcuminoid of turmeric}}{{Distinguish|Curculin}}{{Use American English|date=July 2021}}{{chembox| Verifiedfields = changed| Watchedfields = changed| verifiedrevid = 477166233| Name = Curcumin

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n}}| ImageFile = curcumin.svg| ImageSize =| ImageAlt = Skeletal formula| ImageCaption = Enol form| ImageFile1 = curcuminKeto.svg| ImageSize1 =| ImageAlt1 = Skeletal formula| ImageCaption1 = Keto form| ImageFile2 = Curcumin-enol-3D-balls.png| ImageSize2 =| ImageAlt2 = Ball-and-stick model| ImageFile3 = Curcumin-keto-3D-balls.png| ImageSize3 =| ImageAlt3 = Ball-and-stick model| PIN = (1E,6E)-1,7-Bis(4-hydroxy-3-methoxyphenyl)hepta-1,6-diene-3,5-dione

(1E,6E)-1,7-Bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione

Curcumin I

Natural Yellow 3}}| Section1 = {{Chembox Identifiers

correct|EBI}}| ChEBI = 3962| SMILES = O=C(C=Cc1ccc(O)c(OC)c1)CC(=O)C=Cc2cc(OC)c(O)cc2

correct|chemspider}}| ChemSpiderID = 839564

changed|EBI}}| ChEMBL = 116438

correct|FDA}}| UNII = IT942ZTH98| KEGG = C10443| InChI = 1/C21H20O6/c1-26-20-11-14(5-9-18(20)24)3-7-16(22)13-17(23)8-4-15-6-10-19(25)21(12-15)27-2/h3-12,24-25H,13H2,1-2H3/b7-3+,8-4+| InChIKey = VFLDPWHFBUODDF-FCXRPNKRBF

correct|chemspider}}| StdInChI = 1S/C21H20O6/c1-26-20-11-14(5-9-18(20)24)3-7-16(22)13-17(23)8-4-15-6-10-19(25)21(12-15)27-2/h3-12,24-25H,13H2,1-2H3/b7-3+,8-4+

correct|chemspider}}| StdInChIKey = VFLDPWHFBUODDF-FCXRPNKRSA-N

correct|CAS}}| CASNo = 458-37-7| PubChem = 969516| IUPHAR_ligand = 7000| RTECS = }}| Section2 = {hide}Chembox Properties

H=20|O=6| Appearance = Bright yellow-orange powder| Density =| Solubility =| MeltingPtC = 183| BoilingPt =| pKa = {edih}| Section7 = {{Chembox Hazards| ExternalMSDS =| MainHazards =| FlashPt = }}| Section8 = {{Chembox Related| OtherCpds = }} }}Curcumin is a bright yellow chemical produced by plants of the Curcuma longa species. It is the principal curcuminoid of turmeric (Curcuma longa), a member of the ginger family, Zingiberaceae. It is sold as a herbal supplement, cosmetics ingredient, food flavoring, and food coloring.WEB,weblink The State of the Curcumin Market, Majeed S, December 28, 2015, Natural Products Insider, en-US, dmy, February 29, 2016, October 17, 2017,weblink Chemically, curcumin is a polyphenol, more particularly a diarylheptanoid, belonging to the group of curcuminoids, which are phenolic pigments responsible for the yellow color of turmeric.{{PubChem|969516}}Laboratory and clinical research have not confirmed any medical use for curcumin. It is difficult to study because it is both unstable and poorly bioavailable. It is unlikely to produce useful leads for drug development. History Curcumin was named in 1815 when Henri Auguste Vogel and Pierre Joseph Pelletier reported the first isolation of a "yellow coloring-matter" from the rhizomes of turmeric.JOURNAL, Vogel, A, Pelletier, J, Examen chimique de la racine de Curcuma, fr, Chemical examination of turmeric root, Journal de Pharmacie et des Sciences Accessoires, 1, July 1815, 289–300, {{gallica, bpt6k781358/f290.item, |url=https://books.google.com/books?id=dqU8AAAAcAAJ&pg=PA289 }} Later, it was found to be a mixture of resin and turmeric oil. In 1910, Milobedzka and Lampe reported the chemical structure of curcumin to be as diferuloylmethane.BOOK, 10.1016/B978-0-12-815461-8.00002-5, Curcumin: Historical Background, Chemistry, Pharmacological Action, and Potential Therapeutic Value, Curcumin for Neurological and Psychiatric Disorders, 2019, Farooqui, Tahira, Farooqui, Akhlaq A., 23–44, 978-0-12-815461-8, 146070671, Later in 1913, the same group accomplished the synthesis of the compound.Although used in traditional medicine, the possible therapeutic properties of turmeric or curcumin remain undetermined.WEB,weblink Turmeric, US National Center for Complementary and Integrative Health, National Institutes of Health, April 2020, 24 October 2023, Uses (File:Kurkumina.jpg|thumb|Curcumin powder)The most common applications are as an ingredient in dietary supplement, in cosmetics, as flavoring for foods, such as turmeric-flavored beverages in South and Southeast Asia, and as coloring for foods, such as curry powders, mustards, butters, and cheeses. As a food additive for orange-yellow coloring in prepared foods, its E number is E{{nbs}}100 in the European Union.WEB, European Commission, European Commission, Food Additives,weblink February 15, 2014, October 8, 2022,weblink WEB,weblink Curcumin, E 100, page 9, Specifications for food additives listed in Annexes II and III to Regulation (EC) No 1333/2008 of the European Parliament, March 9, 2012, July 24, 2019, It is also approved by the U.S. FDA to be used as a food coloring in US.WEB, CFR – Code of Federal Regulations Title 21,weblink www.accessdata.fda.gov, Curcumin is used as a complexometric indicator for boron.WEB,weblink EPA-NERL: 212.3: Boron by Colorimetry – Boron (Colorimetric, Curcumin), 1974, 2024-02-18, National Environmental Methods Index, National Exposure Research Laboratory (EPA-NERL), National Exposure Research Laboratory,weblink 2017-02-03, live, It reacts with boric acid to form a red-colored compound, rosocyanine. Chemistry File:Curcumin thin lipid film.jpg|alt=A bright red substance in a small glass flask, held by gloved fingers|thumb|Curcumin becomes bright red when it interacts electrostatically with a phospholipidphospholipidCurcumin incorporates a seven carbon linker and three major functional groups: an α,β-unsaturated β-diketone moiety and an aromatic O-methoxy-phenolic group. The aromatic ring systems, which are phenols, are connected by two α,β-unsaturated carbonyl groups.JOURNAL, 10.1002/cber.191004302168, Zur Kenntnis des Curcumins, Knowing about curcumin, de, 1910, MiÅ‚obÈ©dzka J, van Kostanecki S, Lampe V, Berichte der Deutschen Chemischen Gesellschaft, 43, 2, 2163–2170,weblink It is a diketone tautomer, existing in enolic form in organic solvents and in keto form in water.JOURNAL, Manolova Y, Deneva V, Antonov L, Drakalska E, Momekova D, Lambov N, The effect of the water on the curcumin tautomerism: a quantitative approach, Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 132, 815–820, November 2014, 24973669, 10.1016/j.saa.2014.05.096,weblink 2014AcSpA.132..815M, 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.{{citation needed|date=September 2021}} Because of its hydrophobic nature, curcumin is poorly soluble in water but is easily soluble in organic solvents. Biosynthesis The biosynthetic route of curcumin is uncertain. In 1973, Peter J. Roughley and Donald A. Whiting proposed two mechanisms for curcumin biosynthesis. The first mechanism involves a chain extension reaction by cinnamic acid and 5 malonyl-CoA molecules that eventually arylize into a curcuminoid. The second mechanism involves two cinnamate units coupled together by malonyl-CoA. Both use cinnamic acid as their starting point, which is derived from the amino acid phenylalanine.Plant biosynthesis starting with cinnamic acid is rare compared to the more common p-coumaric acid.JOURNAL, Kita T, Imai S, Sawada H, Kumagai H, Seto H, The biosynthetic pathway of curcuminoid in turmeric (Curcuma longa) as revealed by 13C-labeled precursors, Bioscience, Biotechnology, and Biochemistry, 72, 7, 1789–1798, July 2008, 18603793, 10.1271/bbb.80075, free, Only a few identified compounds, such as anigorufone and pinosylvin, build from cinnamic acid.JOURNAL, Schmitt B, Hölscher D, Schneider B, Variability of phenylpropanoid precursors in the biosynthesis of phenylphenalenones in Anigozanthos preissii, Phytochemistry, 53, 3, 331–337, February 2000, 10703053, 10.1016/S0031-9422(99)00544-0, JOURNAL, Gehlert R, Schoeppner A, Kindl H, Stilbene Synthase from Seedlings of Pinus sylvestris: Purification and Induction in Response to Fungal Infection, Molecular Plant-Microbe Interactions, 1990, 3, 6, 444–449, 10.1094/MPMI-3-444,weblink {{Annotated image 4| caption = Biosynthetic pathway of curcumin in Curcuma longa.| header =| header_align =| header_background =| alt = Curcumin biosynthesis diagram| image = Curcumin biosynthesis.svg| align = center| image-width = 500| width = 500| height = 491| annot-font-size = 10.5| annot-background-color = white| icon = none| annotations =}} Pharmacology (File:Curcumin fluorescence.jpg|thumb|Curcumin displays green fluorescence under UV light)Curcumin, which shows positive results in most drug discovery assays, is regarded as a false lead that medicinal chemists include among "pan-assay interference compounds". This attracts undue experimental attention while failing to advance as viable therapeutic or drug leads,JOURNAL, Nelson KM, Dahlin JL, Bisson J, Graham J, Pauli GF, Walters MA, The Essential Medicinal Chemistry of Curcumin, Journal of Medicinal Chemistry, 60, 5, 1620–1637, March 2017, 28074653, 5346970, 10.1021/acs.jmedchem.6b00975, See also: JOURNAL, Nelson KM, Dahlin JL, Bisson J, Graham J, Pauli GF, Walters MA, Curcumin May (Not) Defy Science, ACS Medicinal Chemistry Letters, 8, 5, 467–470, May 2017, 28523093, 5430405, 10.1021/acsmedchemlett.7b00139, JOURNAL, Baker M, Deceptive curcumin offers cautionary tale for chemists, Nature, 541, 7636, 144–145, January 2017, 28079090, 10.1038/541144a, 2017Natur.541..144B, free, JOURNAL, Bisson J, McAlpine JB, Friesen JB, Chen SN, Graham J, Pauli GF, Can Invalid Bioactives Undermine Natural Product-Based Drug Discovery?, Journal of Medicinal Chemistry, 59, 5, 1671–1690, March 2016, 26505758, 4791574, 10.1021/acs.jmedchem.5b01009, although some derivatives of curcumin such as EF-24 have seen a significant amount of research.JOURNAL, He, Yonghan, Li, Wen, Hu, Guangrong, Sun, Hui, Kong, Qingpeng, Bioactivities of EF24, a Novel Curcumin Analog: A Review, Frontiers in Oncology, 11 December 2018, 8, 614, 10.3389/fonc.2018.00614, 30619754, 6297553, free, Factors that limit the bioactivity of curcumin or its analogs include chemical instability, water insolubility, absence of potent and selective target activity, low bioavailability, limited tissue distribution, and extensive metabolism. Very little curcumin escapes the GI tract and most is excreted in feces unchanged.JOURNAL, Metzler M, Pfeiffer E, Schulz SI, Dempe JS, Curcumin uptake and metabolism, BioFactors, 39, 1, 14–20, 2013, 22996406, 10.1002/biof.1042, 8763463, If curcumin enters plasma in reasonable amounts, there is a high risk of toxicity since it is promiscuous, and interacts with several proteins known to increase the risk of adverse effects, including hERG, cytochrome P450s, and glutathione S-transferase. Safety As a component of turmeric, curcumin may interact with prescription drugs and dietary supplements.WEB, Turmeric,weblink Drugs.com, November 28, 2018, December 6, 2017, In high amounts, it may be unsafe for women during pregnancy. It may cause side effects, such as nausea, diarrhea, hives, or dizziness. Between 2004 and 2022 there were ten cases of liver injury caused by curcumin herbal and dietary supplements.JOURNAL, Halegoua-DeMarzio, Dina, Navarro, Victor, Ahmad, Jawad, Avula, Bharathi, Barnhart, Huiman, Barritt, A. Sidney, Bonkovsky, Herbert L., Fontana, Robert J., Ghabril, Marwan S., Hoofnagle, Jay H., Khan, Ikhlas A., Kleiner, David E., Phillips, Elizabeth, Stolz, Andrew, Vuppalanchi, Raj, Liver Injury Associated with Turmeric—A Growing Problem: Ten Cases from the Drug-Induced Liver Injury Network [DILIN], The American Journal of Medicine, Elsevier BV, 136, 2, 2023, 0002-9343, 10.1016/j.amjmed.2022.09.026, 200–206, 36252717, 9892270, Curcumin is a contact allergen.JOURNAL, Chaudhari SP, Tam AY, Barr JA, Curcumin: A Contact Allergen, J Clin Aesthet Dermatol, 8, 11, 43–48, November 2015, 26705440, 4689497, The intended use of curcumin as a food additive is generally recognized as safe by the U.S. Food and Drug Administration.WEB, GRAS Notice (GRN) No. 822,weblink U.S. Food & Drug Administration, GRAS Notice Inventory, Medical research Although curcumin has been assessed in numerous laboratory and clinical studies, it has no medical uses established by well-designed clinical research.WEB,weblink Curcumin, Linus Pauling Institute, Oregon State University, Corvallis, Micronutrient Information Center; Phytochemicals, 2016, June 18, 2016, According to a 2017 review of more than 120 studies, curcumin has not been successful in any clinical trial, leading the authors to conclude that "curcumin is an unstable, reactive, non-bioavailable compound and, therefore, a highly improbable lead". Curcumin exhibits numerous interference properties which may lead to misinterpretation of results.NEWS, Lowe, Derek, Curcumin Will Waste Your Time,weblink Science Blogs, 12 January 2017, The US government has supported US$150 million in research into curcumin through the National Center for Complementary and Integrative Health, and no support has been found for curcumin as a medical treatment.NEWS, Lemonick S, Everybody Needs To Stop With This Turmeric Molecule,weblink May 27, 2018, Forbes (magazine), Forbes, January 19, 2017, Research fraud Bharat Aggarwal, a former cancer researcher at the University of Texas MD Anderson Cancer Center, had 29 papers retracted due to research fraud {{as of | July 2021 | lc=yes}}.WEB, The Retraction Watch Leaderboard,weblink Retraction Watch, 28 July 2021, 16 June 2015, WEB,weblink M.D. Anderson professor under fraud probe, Ackerman T, Houston Chronicle, February 29, 2012, March 8, 2016, NEWS, Caught Our Notice: Researcher who once threatened to sue Retraction Watch now up to 19 retractions,weblink Retraction Watch, April 10, 2018, Aggarwal's research had focused on potential anti-cancer properties of herbs and spices, particularly curcumin, and according to a March 2016 article in the Houston Chronicle, "attracted national media interest and laid the groundwork for ongoing clinical trials".NEWS, Ackerman T, M.D. Anderson scientist, accused of manipulating data, retires,weblink Houston Chronicle, March 2, 2016, JOURNAL, Spice Healer, Stix G, Scientific American, February 2007, 296, 2, 66–69, 10.1038/scientificamerican0207-66, 17367023, 2007SciAm.296b..66S, NEWS,weblink In cancer fight, a spice brings hope to the table, Ackerman T, Houston Chronicle, July 11, 2005, March 24, 2015, Aggarwal cofounded a company in 2004 called Curry Pharmaceuticals based in Research Triangle Park, North Carolina, which planned to develop drugs based on synthetic analogs of curcumin.JOURNAL, Singh S, From exotic spice to modern drug?, Cell, 130, 5, 765–768, September 2007, 17803897, 10.1016/j.cell.2007.08.024, 16044143, free, SignPath Pharma, a company seeking to develop liposomal formulations of curcumin, licensed three patents by Aggarwal related to that approach from MD Anderson in 2013.NEWS, Baum S, Biotech startup raises $1M for lung cancer treatment using component of tumeric,weblink Med City News, March 26, 2013, FDA warnings about dietary supplements Between 2018 and 2023, the FDA issued 29 warning letters to American manufacturers of dietary supplements for making false claims of anti-disease effects from using products containing curcumin.WEB, Warning Letters: Curcumin (search term),weblink US Food and Drug Administration, 23 April 2023, 23 April 2023, In each letter, the FDA stated that the supplement product was not an approved new drug because the "product is not generally recognized as safe and effective" for the advertised uses, that "new drugs may not be legally introduced or delivered for introduction into interstate commerce without prior approval from FDA", and that the "FDA approves a new drug on the basis of scientific data and information demonstrating that the drug is safe and effective". Alternative medicine Though there is no evidence for the safety or efficacy of using curcumin as a therapy, some alternative medicine practitioners give it intravenously, supposedly as a treatment for numerous diseases.WEB,weblink Food and Drug Administration, FDA investigates two serious adverse events associated with ImprimisRx's compounded curcumin emulsion product for injection, August 4, 2017, NEWS, Hermes BM, Britt Marie Hermes, Naturopathic Doctors Look Bad After California Woman Dies From Turmeric Injection,weblink May 12, 2017, Forbes, March 27, 2017, NEWS, Hermes BM, Confirmed: Licensed Naturopathic Doctor Gave Lethal 'Turmeric' Injection,weblink December 9, 2017, Forbes (magazine), Forbes, April 10, 2017, In 2017, two serious cases of adverse events were reported from curcumin or turmeric products—one severe allergic reaction and one death—that were caused by administration of a curcumin-polyethylene glycol (PEG40) emulsion product by a naturopath. One treatment caused anaphylaxis leading to death. Stability Decontamination of food by ionizing radiation, or food irradiation, is considered a safe and efficient process for elimination of pathogenic bacteria.JOURNAL, Cosentino, Helio M., Takinami, Patricia Y.I., del Mastro, Nelida L., 2016, Comparison of the ionizing radiation effects on cochineal, annatto and turmeric natural dyes,weblink Radiation Physics and Chemistry, en, 124, 208–211, 10.1016/j.radphyschem.2015.09.016, 2016RaPC..124..208C, JOURNAL, Farkas, József, Mohácsi-Farkas, Csilla, 2011, History and future of food irradiation,weblink Trends in Food Science & Technology, en, 22, 2–3, 121–126, 10.1016/j.tifs.2010.04.002, Ionizing radiation treatment can be applied to either raw materials or ready to eat foods, with some countries, like the United States, imposing limitations on its use.WEB, Code of Federal Regulations: Title 21, Section 179.26,weblink U.S. Food and Drug Administration, 7 Feb 2022, In 2016, laboratory research established and compared the radiosensitivity of three organic food colorants including curcumin, carmine, and annatto to create data to be used for application whenever food products containing these food colors were to undergo the radiation process. The researchers used spectrophotometry and capillary electrophoresis to establish radiosensitivity of the three organic food colorants. Carmine samples were quite stable against radiation treatment, annatto showed limited stability, and curcumin was found to be stable at high temperatures and in acids, but unstable in alkaline conditions and in the presence of light. References {{Reflist}} External links Curcumin (Curcuma, Turmeric) and Cancer (PDQ®)–Health Professional Version Medicines containing turmeric or curcumin, risk of liver injury, Safety advisory First draft statement on the potential risk to human health of turmeric and curcumin {{Curcuminoid}}{{HDAC inhibitors}}{{Leukotriene signaling modulators}}{{Prostanoid signaling modulators}}{{Transient receptor potential channel modulators}}