Antimutagenic activity of falcarindiol from Peucedanum praeruptorum

A methanol extract from Peucedanum praeruptorum showed a suppressive effect on umu gene expression of the SOS response in Salmonella typhimurium TA1535/pSK1002 against the mutagen 2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide (furylfuramide). The methanol extract from P. praeruptorum was re-extracted with hexane, dichloromethane, n-butanol, and water, respectively. A suppressive compound in the hexane extract fraction was isolated by SiO2 column chromatography and identified as falcarindiol by EI-MS, IR, and H-1 and C-13 NMR spectroscopy. Falcarindiol exhibited an inhibition of the SOS-inducing activity of furylfuramide in the umu test. Gene expression was suppressed 75% at less than 0.15 mu mol/mL, and the ID50 value was 0.10 mu mol/mL. The diacetate compound of falcarindiol did not show any suppressive effect on the SOS induction of furylfuramide. Falcarindiol was also assayed with the mutagen 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1), which requires liver-metabolizing enzymes, and showed a suppressive effect similar to that with furylfuramide. The falcarindiol ID50 value versus Trp-P-1 was 0.096 mu mol/mL. The antimutagenic activities of falcarindiol and falcarindiol diacetate against furylfuramide and Trp-P-1 were tested by an Ames test using S. typhimurium TA100, which indicated that falcarindiol suppressed the mutagenicity of furylfuramide and Trp-P-1 and falcarindiol diacetate suppressed the mutagenicity of Trp-P-1.