灯盏生脉胶囊有效组分对大鼠细胞色素P450酶同工酶作用的体外研究

The interaction between the active components of Dengzhanshengmai Capsule and CYP450 enzymes in rats in vitro

目的探讨灯盏生脉胶囊6种有效组分对细胞色素P450酶(CYP450酶)4种主要亚型(同工酶)的作用。方法采用大鼠肝微粒体体外孵育的方法和液质联用(LC/MS/MS)技术,通过体外cocktail高通量筛选,选择不同的CYP450酶同工酶特异性探针底物与灯盏生脉有效组分共同孵育,比较灯盏生脉有效组分对大鼠肝微粒体中CYP450酶同工酶抑制作用。结果五味子甲素对大鼠肝微粒体CYP3A1、2C6及2C11有弱抑制作用,五味子酯甲对CYP3A1及2C11有弱抑制作用,IC50值均在10～50μmol/L之间。结论本研究初步界定参与灯盏生脉胶囊有效组分代谢的大鼠CYP450酶同工酶,及其有效组分对大鼠CYP450酶同工酶的抑制作用,为灯盏生脉胶囊与其他药物的联合使用提供科学依据。

Objective To study the interactions between 6 components of Dengzhanshengmai Capsule and 4 isoenzymes of cytochrome P450 （CYP450） in vitro. Methods CYP450 isoenzymes, which were involved in drug metabolism, were attained from rat hepatic microsomes with liquid chromatographymass spectrometry （LC/MS/MS）. Efficacies on enzyme inhabitation of the 6 effective components of Dengzhanshengmai Capsule were assessed. Restflts Mild inhibitory effects on rat liver microsomal CYP3A1,2C6 and 2C11 were found in Sehizandrin A. Meanwhile, mild inhibitory effects on rat liver CYP3A1 and 2Cll were found in Schisantherin A, with both IC50 values between 10 and 50 μmol/L. Conclusion In the study, primary evaluation of inhibitory efficacy of Dengzhanshengmai Capsule on CYP450 isoenzymes is carried out, providing evidences for further application of Dengzhanshengmai Capsule in treatment.