Protective activities of some phenolic 1,3-diketones against lipid peroxidation: possible involvement of the 1,3-diketone moiety.

The protective activities of four ginger-derived phenolic 1,3-diketones (1-4) and curcumin (5) against lipid peroxidation was studied by using different biologically relevant model systems and pulse radiolysis. The extraordinary activity of 5 vis-à-vis 1-4 against Fe(2+)-mediated peroxidation may be attributed to the additional phenolic hydroxy group in the former, which lends it better iron-chelating and radical-scavenging properties. In iron-independent peroxidation, however, the ginger constituent [6]-dehydrogingerdione (1) showed activity comparable to that of 5; this indicates its higher affinity for the lipid peroxide radical (LOO(.)), due to its higher hydrophobicity. A very high rate constant for the reaction between 1 and Cl(3)COO(.), measured by pulse radiolysis, not only confirmed this, but also established the superior antioxidant efficacy of 1 in comparison to vitamins E and C. This was also evident from the results obtained from a liposomal peroxidation study with 1 and vitamin C. This study also established a synergistic effect of the latter on the antioxidant activity of 1. HPLC analysis of the products of the reaction between 1 and Cl(3)COO(.) revealed the formation of higher concentrations of ferulic acid (7), along with vanillin (6). The presence of ascorbate affected the generation of 7 more than it did that of 6. On this basis, a mechanism for the antioxidant action of 1 has been proposed, which suggests the contribution of the phenolic group as well as the active methylene group of the 1,3-diketones.