Sugiyama Y, Kawakishi S, Osawa T
Department of Applied Biological Sciences, Nagoya University, Japan.
Biochem Pharmacol. 1996 Aug 23;52(4):519-25. 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 tertbutylhydroperoxide. 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 beta-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 beta-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 beta-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 beta-diketone moiety as well as phenolic hydroxy groups.
我们研究了姜黄素及其主要代谢产物之一四氢姜黄素（THC）对叔丁基过氧化氢诱导的红细胞膜空泡脂质过氧化的抑制作用。结果表明，THC的抑制作用比姜黄素更强。为了研究其抗氧化活性机制，我们检测了几种抑制剂的作用，如抗氧化酶、羟基自由基清除剂、单线态氧猝灭剂和金属离子螯合剂。由于所有抑制剂均未能抑制膜过氧化，因此THC必定能清除诸如叔丁氧基自由基和过氧自由基等自由基。为了阐明THC的抗氧化机制，特别是β-二酮部分的作用，将二甲基化的THC与2,2'-偶氮二（2,4-二甲基戊腈）热解产生的过氧自由基一起孵育。检测到四种氧化产物，其中三种被鉴定为3,4-二甲氧基苯甲酸、3',4'-二甲氧基苯乙酮和3-(3,4-二甲氧基苯基)丙酸。第四种氧化产物似乎是一种不稳定的中间体，其详细结构尚未确定。这些结果表明，THC的β-二酮部分必定通过β-二酮部分中两个羰基之间活性亚甲基碳上的C-C键断裂来表现出抗氧化活性。由于THC是姜黄素的主要代谢产物之一，它在体内可能也会通过β-二酮部分以及酚羟基表现出与姜黄素活性形式相同的生理和药理特性。
