Regioselective Hydroxylation of Oleanolic Acid Catalyzed by Human CYP3A4 to Produce Hederagenenin, a Chiral Metabolite

Oleanolic acid (OA) is a pentacyclic triterpenoid widely found in plants and foods as an aglycone of saponins or free acid. OA exhibits beneficial activities for humans, including antitumor, antivirus, hepatoprotection properties without apparent toxicity. The metabolites produced by the cytochrome P450 (P450) enzymes are critical evaluation efficacy safety drugs. In this study, potential were investigated P450-catalyzed oxidation reactions. Among various tested human P450s, only CYP3A4 was active hydroxylation OA. major metabolite characterized set analyses using HPLC, LC–MS, NMR. It to be 4-epi-hederagenenin, chiral product, regioselective methyl group at C-23 position. These results indicated that can hydroxylate substrate make 4-epi-hederagenenin. Possible drug–food interactions discussed.