Chemically, curcumin is apolyphenol, more particularly adiarylheptanoid, belonging to the group of curcuminoids, which arephenolicpigments responsible for the yellow color of turmeric.[2]
Extensive studies have consistently failed to show any medical value for curcumin. It is difficult to study because it is both unstable and poorlybioavailable. It is unlikely to produce useful leads fordrug development as alead compound.[3]
Curcumin was named in 1815 when Henri Auguste Vogel andPierre Joseph Pelletier reported the first isolation of a "yellow coloring-matter" from therhizomes of turmeric.[4] Later, it was found to be a mixture ofresin and turmeric oil. In 1910, Milobedzka and Lampe reported the chemical structure of curcumin to be as diferuloylmethane.[5] Later in 1913, the same group accomplished the synthesis of the compound.
Although used intraditional medicine, the possible therapeutic properties of turmeric or curcumin remain undetermined.[3][6][7]
Curcumin incorporates a seven carbon linker and three major functional groups: an α,β-unsaturated β-diketone moiety and an aromatic O-methoxy-phenolic group.[2][5] The aromatic ring systems, which arephenols, are connected by two α,β-unsaturatedcarbonyl groups.[2][11] It is adiketonetautomer, existing inenolic form inorganic solvents and inketo form in water.[12] The diketones form stable enols and are readily deprotonated to formenolates, which bind metal ions to formacetylacetonate-like complexes.[13] Its complexing properties are manifesting in its reaction withboric acid to give a red-coloredrosocyanine.[2][14]
Because of its hydrophobic nature, curcumin is poorly soluble in water[2] but is easily soluble in organic solvents.[5]
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 bycinnamic acid and 5malonyl-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 acidphenylalanine.[15]
Plant biosynthesis starting with cinnamic acid is rare compared to the more commonp-coumaric acid.[15] Only a few identified compounds, such asanigorufone andpinosylvin, build from cinnamic acid.[16][17]
Curcumin displays green fluorescence under UV light
Curcumin, which shows positive results in mostdrug discovery assays, is regarded as a false lead thatmedicinal chemists include among "pan-assay interference compounds". This attracts undue experimental attention while failing to advance as viable therapeutic or drug leads,[3][6][18] although some derivatives of curcumin such asEF-24 have been well-studied.[19]
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.[3] Very little curcumin escapes theGI tract and most is excreted in feces unchanged.[20] 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, includinghERG,cytochrome P450s, andglutathione S-transferase.[3]
Although curcumin has been assessed in numerous laboratory andclinical studies, it has no medical uses.[21] Its instability,reactivity, and poor bioavailability, make curcumin an unlikely drug candidate.[3] Curcumin exhibits numerous interference properties which may lead to misinterpretation of results.[3][6][22]
Between 1995 and 2017, the US government funded US$150 million in biomedical research into curcumin through theNational Center for Complementary and Integrative Health. No support was found for curcumin as a medical treatment.[3]As a component of turmeric, curcumin may interact withprescription drugs and dietary supplements.[23] In high amounts, it may be unsafe for women during pregnancy.[23] It may cause side effects, such asnausea,diarrhea,hives, or dizziness.[23] Between 2004 and 2022 there were ten cases of liver injury caused by curcumin herbal and dietary supplements.[24] Curcumin is acontact allergen.[25]
Aggarwal cofounded a company in 2004 called Curry Pharmaceuticals based inResearch Triangle Park,North Carolina, which planned to develop drugs based on synthetic analogs of curcumin.[31][33] SignPath Pharma, a company seeking to developliposomal formulations of curcumin, licensed three patents by Aggarwal related to that approach from MD Anderson in 2013.[34]
Between 2018 and 2023, the U.S. FDA issued 29warning letters to American manufacturers ofdietary supplements for making false claims of anti-disease effects from using products containing curcumin.[35] In each letter, the FDA stated that the supplement product was not anapproved 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".[35]
In 2016, laboratory research established and compared theradiosensitivity of three organic food colorants including curcumin,carmine, andannatto to create data to be used for application whenever food products containing these food colors were to undergo the radiation process.[39] The researchers usedspectrophotometry andcapillary 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 unstable, particularly when diluted.[39]
^"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. RetrievedJuly 24, 2019.
^Pham, Chien Thang; Pham, Thu Thuy; Nguyen, Hung Huy; Trieu, Thi Nguyet (2020). "Syntheses, Structures, and Bioactivities Evaluation of some Transition Metal Complexes with 4,4'-Diacetylcurcumin".Zeitschrift für Anorganische und Allgemeine Chemie.646 (11–12):495–499.Bibcode:2020ZAACh.646..495P.doi:10.1002/zaac.202000088.
^"Curcumin".Micronutrient Information Center; Phytochemicals. Linus Pauling Institute, Oregon State University, Corvallis. 2016. RetrievedJune 18, 2016.
