Involvement of the β-diketone moiety in the antioxidative mechanism of tetrahydrocurcumin

Article abstract of DOI:10.1016/0006-2952(96)00302-4

We examined the inhibitory effects of curcumin and tetrahydrocurcumin (THC), one of the major metabolites of curcumin, on the lipid peroxidation of erythrocyte membrane ghosts induced by tert-butylhydroperoxide. The results demonstrated that THC showed a greater inhibitory effect than curcumin. To investigate the mechanism of antioxidative activity, we examined the effects of several inhibitors, such as antioxidant enzymes, hydroxyl radical scavengers, ¹O₂ quencher, and chelating agents for metal ions. Given that all inhibitors failed to inhibit membrane peroxidation, THC must scavenge radicals such as tert-butoxyl radical and peroxyl radical. To clarify the antioxidative mechanism of THC, in particular the role of the β-diketone moiety, dimethylated THC was incubated with peroxyl radicals generated by thermolysis of 2,2'-azobis(2,4-dimethylvaleronitrile). Four oxidation products were detected, three of which were identified as 3,4-dimethoxybenzoic acid, 3',4'-dimethoxyacetophenone, and 3-(3,4-dimethoxyphenyl)-propionic acid. The fourth oxidation product seems to be an unstable intermediate, and its detailed structure has not been determined. These results suggest that the β-diketone moiety of THC must exhibit antioxidative activity by cleavage of the C-C bond at the active methylene carbon between two carbonyls in the β-diketone moiety. Because THC is one of the major metabolites of curcumin, it may also exhibit the same physiological and pharmacological properties as the active form of curcumin in vivo by means of the β-diketone moiety as well as phenolic hydroxy groups.