Assessment of cytochrome P450 inhibition and induction potential of lupeol and betulin in rat liver microsomes.

Abstract

Lupeol and betulin are triterpenoids that are majorly found in dietary substances. The aim of present study was to investigate the inhibition and induction potential of lupeol and betulin on cytochrome P450 (CYP)1A2, CYP2C11, CYP2D6 and CYP3A2 activities in rat liver microsomes. The inhibition and induction studies were conducted using ethoxy resorufin-O-deethylase (CYP1A2), tolbutamide hydroxylase (CYP2C9), and midazolam hydroxylase (CYP3A4) activity assays. In vitro inhibition study was evaluated by incubating lupeol and betulin (1, 3, 10, 30 and 100 μM) with rat liver microsomes, and the metabolite formation was analyzed by high-performance liquid chromatography. The induction study was conducted by administering lupeol (20 mg/kg) and betulin (50 mg/kg) intraperitoneally for 14 days to rats followed by liver isolation and microsome preparation. The IC50 values in inhibition studies were found to be 59.42 μM (CYP1A2), >100 μM (CYP2C11, CYP2D6, CYP3A2) for lupeol, 52.24 μM (CYP1A2), and >100 μM (CYP2C9, CYP2D6, CYP3A2) for betulin. There was no significant modification observed in the CYP450 isoforms, indicating neither inhibition nor induction potential of lupeol and betulin. Lupeol and betulin have very low propensity to interact with CYP enzyme, suggesting no CYP inhibitory and inducing potential in rat liver microsomes.