Differential inductive profiles of hepatic cytochrome P450s by the extracts of Sophora flavescens in male and female C57BL/6JNarl mice

Abstract

Aim of the study Sophora flavescens has been used as an antipyretic and analgesic agent. To assess the possible herb–drug interaction, effects of S. flavescens extracts on hepatic cytochrome P450 (P450, CYP) enzymes were studied. Materials and methods Effects of the extracts prepared by three different pharmaceutical companies on P450 enzymes were investigated in male and female C57BL/6JNarl mice. Results In male mice, extract 1 caused a dose- and time-dependent increase of 7-ethoxyresorufin O-deethylation (EROD) activity. Three-day treatment with 3 g/kg extracts 1–3 elevated EROD, 7-pentoxyresorufin O-dealkylation (PROD), coumarin hydroxylation, and nifedipine oxidation (NFO) activities. In female mice, extracts 1 and 2 increased EROD and PROD activities without affecting coumarin hydroxylation and NFO activities. However, extract 3, which lacked prenylated flavonoids, caused an induction profile in females the same as in males. Treatment with extract 3 fortified with prenylated flavonoids restored the gender difference. An alkaloid, oxymatrine was present in all extracts and increased EROD and PROD activities. At a human equivalent dose (0.18 g/(kg day)), all extracts increased EROD activity. Conclusions These results revealed that Cyp1a had a lower induction response threshold. Oxymatrine contributed at least partly to the P450 induction by S. flavescens. At a higher dose, Cyp2a, Cyp2b, and Cyp3a could be induced and the male-specific induction of Cyp2a and Cyp3a was associated with the presence of prenylated flavonoids.