Antimutagenic Activity of (+)-Polyalthic Acid from Vitex rotundiforia

Abstract

A methanol extract from Vitex rotundiforia showed a suppressive effect on umu gene expression of the SOS response in Salmonella typhimurium TA1535/pSK1002 against the mutagen (3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1)), which requires liver metabolizing enzymes. The methanol extract from V. rotundiforia was re-extracted with dichloromethane, n-butanol, and water, respectively. A suppressive compound in the dichloromethane extract fraction was isolated by SiO 2 column chromatography and identified as (+)-polyalthic acid by EI-MS and 1 H and 13 C NMR spectroscopy. (+)-Polyalthic acid suppressed the SOS-inducing activity of Trp-P-1 in the umu test. Gene expression was suppressed 90% at <0.32 μmol/mL, and the ID 50 value was 0.19 μmol/mL. (+)-Methyl polyalthate also suppressed the SOS-inducing activity of Trp-P-1 in the umu test. Gene expression was suppressed 57% at <0.32 μmol/mL, and the ID 50 value was 0.29 μmol/mL. (+)-Polyalthic acid and (+)-methyl polyalthate were also assayed with the mutagens 2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide (furylfuramide) and activated Trp-P-1, but these compounds did not show a suppressive effect on the SOS induction of these mutagens. The antimutagenic activities of (+)-polyalthic acid and (+)-methyl polyalthate against Trp-P-1, furylfuramide, and activated Trp-P-1 were tested by an Ames test using S. typhimurium TA100. The results indicated that (+)-polyalthic acid suppressed the mutagenicity of Trp-P-1 and the mutagenicity of activated Trp-P-1 and (+)-methyl polyalthate suppressed the mutagenicity of Trp-P-1.