Antimutagenic activity of flavonoids from Pogostemon cablin

A methanol extract from Pogostemon cablin showed a suppressive effect on um u gene expression of SOS response in Salmonella typhimurium TA1535/pSK1002 against the mutagen 2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide (furylfuramid e). The methanol extract was re-extracted with hexane, dichloromethane, but anol, and water. A dichloromethane fraction showed a suppressive effect. Su ppressive compounds against furylfuramide in the dichloromethane fraction w ere isolated by SiO2 column chromatography and identified as: 7,4'-di-O-met hyleriodictyol (1), 7,3',4'-tri-O-methyleriodictyol (2), and 3,7,4'-tri-O-m ethylkaempferol (3). In addition, three flavonoids, ombuine (4), pachypodol (5), and kumatakenin (6), were isolated and identified from the dichrolomet hane fraction. Compounds 1 and 3 suppressed >50% of the SOS-inducing activi ty at <0.6 mu mol/mL, and the ID50 values of both compounds were 0.25 mu mo l/mL. Compound 2 showed a weakly suppressive effect (17%) at a concentratio n of 0.6 mu mol/mL, and compounds 4-6 did not. These compounds were also as sayed with 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1), which req uires liver metabolizing enzymes. Compounds 3-6 suppressed >80% of the SOS- inducing activity of Trp-P-1 at <0.06 mu mol/mL, and compounds 1 and 2 supp ressed 87 and 63% at a concentration of 0.3 mu mol/mL. In addition, these c ompounds were assayed with activated Trp-P-1, and the suppressed effects of these compounds were further decreased when compared to Trp-P-1. The antim utagenic activities of these compounds against furylfuramide, Trp-P-1, and activated Trp-P-1 were assayed by the Ames test using S. typhimurium TA100.