A Curcumin Degradation Product, 7-Norcyclopentadione, Formed by Aryl Migration and Loss of a Carbon from the Heptadienedione Chain

Abstract

Evidence that anti-inflammatory and other biological effects of curcumin may at least in part be mediated by its metabolites underscores the importance of identifying novel transformation products. Spontaneous degradation of curcumin in buffer pH 7.5 results mainly in dioxygenated products with a characteristic cyclopentadione ring comprised of carbons 2 through 6 of the former heptadienedione chain. When analyzing degradation reactions of 4’-O-methylcurcumin a product was identified missing one of the terminal carbons of the heptadienedione moiety while containing a cyclopentadione ring and adjacent hydroxyl group typical of curcumin degradation products. Analysis of curcumin autoxidation reactions showed formation of an analogous compound, 7-norcyclopentadione, a degradation product exhibiting net loss of a carbon and gain of an oxygen atom. Removal of the carbon is proposed to occur via a peroxide-linked curcumin dimer in conjunction with radical mediated 1,2-aryl migration of a guaiacol moiety. Oxidation reactions of demethoxycurcumin gave demethoxy-7-norcyclopentadione whereas an analogous product was not observed from bis-demethoxycurcumin. Incubation of RAW264.7 macrophage-like cells with curcumin showed presence of 7-norcyclopentadione the formation of which was not increased upon activation of the cells with 12-O-tetradecanoylphorbol-13-acetate (PMA). 7-Norcyclopentadione is a novel type of degradation product that is most likely formed via autoxidative processes when cells are incubated with curcumin.

Poly(pro-curcumin) Materials Exhibit Dual Release Rates and Prolonged Antioxidant Activity as Thin Films and Self-Assembled Particles

“…At predetermined time points, the supernatant buffer was collected for analysis, and the amount of curcumin in the supernatant was calculated on the basis of the absorbance relative to a calibration curve. Native curcumin is highly unstable in PBS; it undergoes rapid auto-oxidation in the presence of water and dissolved oxygen, which produces a variety of byproducts on the time scale of minutes. − The composition of curcumin auto-oxidation products is related to the time of incubation and has been well studied by Schneider and co-workers. − Native, unmodified curcumin in aqueous solution has the maximum absorption at 423 nm, which decays significantly after just 10 min in PBS at 37 °C (Figure A). Following auto-oxidation, new absorption peaks appear at 227, 264, and 366 nm.…”