Metabolic detoxification of bakuchiol is mediated by oxidation of CYP 450s in liver microsomes

Bakuchiol, one of bioactive compounds isolated from the dried ripe fruits of Psoralea corylifolia L., possesses a variety of pharmacological activities. In this study, the metabolites of bakuchiol in rat liver microsomes as well as their cytotoxicities were studied. A total of eight metabolites were isolated and identified as 14-carboxylbakuchiol (M1), 14,15-dihydroxybakuchiol (M2), 12,13-dihydroxybakuchiol (M3), 15-hydroxybakuchiol (M4), 14-hydroxybakuchiol (M5), bakuchiol hydrate (M6), 15-hydroxybakuchiol acetate (M7), and 14-hydroxybakuchiol acetate (M8). All the metabolites are new compounds except for M3. The main type of biotransformation is oxidation reaction, including hydroxylation, epoxidation and carboxylation. Cytotoxicities of bakuchiol and its metabolites against human kidney-2 (HK-2) cell line were evaluated. The median inhibition concentration (IC50) values of bakuchiol, M4, M6 and M8 were (29.48 +/- 0.22) mu M, (67.51 +/- 6.80) mu M, (90.23 +/- 3.89) mu M, and (86.62 +/- 6.08) mu M, respectively, and the IC50 values of M1, M2, M3, M5, and M7 were all in excess of 100 mu M. To further verify the metabolic reliability, the metabolits of bakuchiol in vivo and the metabolic species variations in human and rat liver microsomes were studied using UPLC-MS/MS method. This study provides valuable information for further investigation of metabolism and toxicity of bakuchiol in vivo.