Chemically, curcumin is a polyphenol, more particularly a diarylheptanoid, belonging to the group of curcuminoids, which are phenolicpigments responsible for the yellow color of turmeric.[2]
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 as a lead compound.[3]
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.[4] 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.[5] 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.[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 are phenols, are connected by two α,β-unsaturated carbonyl groups.[2][12] It is a diketonetautomer, existing in enolic form in organic solvents and in keto form in water.[13] 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] Because of its hydrophobic nature, curcumin is poorly soluble in water[2] but is easily soluble in organic solvents.[5]
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.[14]
Plant biosynthesis starting with cinnamic acid is rare compared to the more common p-coumaric acid.[14] Only a few identified compounds, such as anigorufone and pinosylvin, build from cinnamic acid.[15][16]
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,[3][6][17] although some derivatives of curcumin such as EF-24 have seen a significant amount of research.[18]
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 the GI tract and most is excreted in feces unchanged.[19] 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.[3]
Safety
As a component of turmeric, curcumin may interact with prescription drugs and dietary supplements.[20] In high amounts, it may be unsafe for women during pregnancy.[20] It may cause side effects, such as nausea, diarrhea, hives, or dizziness.[20] Between 2004 and 2022 there were ten cases of liver injury caused by curcumin herbal and dietary supplements.[21] Curcumin is a contact allergen.[22]
Although curcumin has been assessed in numerous laboratory and clinical studies, it has no medical uses established by well-designed clinical research.[24] 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".[3] Curcumin exhibits numerous interference properties which may lead to misinterpretation of results.[3][6][25]
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.[31][33] 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.[34]
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.[35] 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".[35]
Decontamination of food by ionizing radiation, or food irradiation, is considered a safe and efficient process for elimination of pathogenic bacteria.[39][40] 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.[39][41] 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.[39] 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 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. Retrieved July 24, 2019.
↑ "Curcumin". Micronutrient Information Center; Phytochemicals. Linus Pauling Institute, Oregon State University, Corvallis. 2016. Retrieved June 18, 2016.
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