ABSTRACT
Objective::To evaluate the effects of Valeriana amurensis roots and rhizomes extract and its active constituents on the activities of six major cytochrome P450 (CYP450) enzymes in human liver microsomes. Method::Coumarin, bupropion, tolbutamide, omeprazole, dextromethorphan and testosterone were used as probe substrates for CYP2A6, CYP2B6, CYP2C9, CYP2C19, CYP2D6 and CYP3A4, respectively. Taking their specific metabolites of hydroxylation or demethylation (7-hydroxycoumarin, hydroxybupropion, 4-hydroxytolbutamide, 5-hydroxyomeprazole, dextromethorphan, 6β-hydroxytestosterone) as indicators of enzyme activities. The analytical indexes were used to establish an in vitro model of human liver microsomes of Cocktail probe substrates. This method was applied to evaluate the effects of V. amurensis roots and rhizomes extract and its active constituents on human liver microsomal enzymes. Result::The V. amurensis roots and rhizomes extract had different inhibitory effects on CYP2B6, CYP2C9, CYP2D6 and CYP3A4, their half-inhibitory concentration (IC50) values were 87.49, 1.73, 68.29, 2.80 mg·L-1, respectively. Among the 9 lignans, (-)-massoniresinol-3α-O-β-D-glucopyranoside had a moderate inhibitory effect on CYP2A6 with an IC50 value of 8.51 μmol·L-1, 8, 8′-dihydroxypinoresinol-4, 4′-di-O-β-D-glucopyranoside had a moderate inhibitory effect on CYP2D6 with an IC50 value of 8.73 μmol·L-1, (+)-medioresinol-4, 4′-O-di-β-D-glucopyranoside had a moderate inhibitory effect on CYP2B6 and CYP2C9 with IC50 values of 5.41 μmol·L-1 and 8.20 μmol·L-1. Conclusion::The V. amurensis roots and rhizomes extract and its active constituents have inhibitory effects on liver CYP450 enzymes. Therefore, in the clinical study of new drugs, it is necessary to fully evaluate the risk of drug interactions caused by combination therapy.