Suppression of the SOS-Inducing Activity of Mutagenic Heterocyclic Amine, Trp-P-1, by Triterpenoid from Uncaria sinensis in the Salmonella typhimurium TA1535/pSK1002 Umu Test

Abstract

The methanol extract from Uncaria sinensis 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[4,3b]indole (Trp-P-1), which requires liver metabolizing enzymes. The methanol extract from U. sinensis was re-extracted with hexane, CH2Cl2, BuOH, and water, respectively. CH2Cl2 extract showed a suppressive effect. A suppressive compound 1 in CH2Cl2 extract was isolated by SiO2 column chromatography. Compound 1 was identified as ursolic acid by IR, electron ionization EI-MS, and NMR spectroscopy. Suppressive effects of ursolic acid (1) and its derivatives, methyl ursolate (1M), acetylursolic acid (1A), and methyl acetylursolate (1MA), were determined in the umu test. These compounds suppressed 61.3, 37.7, 71.5, and 37.8% of the Trp-P-1-induced SOS response at a concentration of 0.4 micromol/mL, respectively. The ID50 values of compounds 1 and 1A were 0.17 and 0.20 micromol/mL. In addition, these compounds were assayed with the activated Trp-P-1. Suppressive effects on activated Trp-P-1 were decreased as compared with those of Trp-P-1.