黄芪甲苷对大鼠肝微粒体酶活性影响

目的:研究黄芪甲苷对CYP450酶的影响,为制定合理用药方案提供科学依据。方法:以甲苯磺丁脲、氯唑沙宗、香豆素、硝苯地平、非那西丁为探针药,HPLC测定探针药与相应代谢产物的浓度,在体外的孵育体系中研究黄芪甲苷对CPY2C9,CPY2E1,CPY2A6,CPY3A4和CPY1A2酶活性的影响。结果:黄芪甲苷对CYP1A2,CYP2A6,CYP2E1酶的活性没有明显的影响,而对CYP2C9和CYP3A4酶的IC50分别为35.40,88.22μmol.L-1。结论:黄芪甲苷对CYP2C9和CYP3A4酶有明显的抑制作用,在与经由CYP2C9,CYP3A4酶代谢的药物合用时,可能会产生药物相互作用。

Inhibitory effects of astragaloside IV on cytochrome P450 enzyme of rat liver microsomes

Objective: To provide a scientific basis for the drug-combination and aim to examine whether astragaloside IV has the impact on the cytochrome P450 enzymes.Method: Tolbutamide,chlorzoxazone,coumarin,nifedipine,and phenacetin were as probe substrates of rat CYP2C9,CYP2E1,CYP2A6,CYP3A4,and CYP1A2,and were incubated in rat liver microsomes with astragaloside IV.Triplicate samples were run to generate IC50 value by incubating P450 probe substrates in the presence of five concentrations of astragaloside IV in the incubation mixture.The Ki values were determined by fitting the probe substrate at various inhibitor concentrations to the equations for competitive inhibition,noncompetitive inhibition,noncompetitive inhibition,and mixed-type inhibition.Result: IC50 and Ki values were estimated,and the types of inhibition were determined.Among the five probe substrates,astragaloside IV might not significantly affect CYP2E1,CYP2A6 and CYP1A2-mediated metabolism in rats,but was a competitive inhibitor of CYP2C9(IC50 35.40 μmol·L-1,Ki 42.88 μmol·L-1),and was a uncompetitive inhibitor of CYP3A4(IC50 88.24 μmol·L-1,Ki 33.31 μmol·L-1).Conclusion: These results suggested that astragaloside IV inhibited CYP2C9 and CYP3A4,which provided useful information for safe and effective use of astragaloside IV.