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目的:研究复方丹参滴丸对参与氯吡格雷代谢酶人源肝羧酸酯酶CES1、细胞色素CYP450 3A4、CYP4502C19、CYP450 1A2、CYP450 2B6的影响,对其作用效应进行整体分析。方法:选择了上述5个氯吡格雷代谢相关靶点,构建组方化学成分分子配体,采用计算药理学方法探讨配体与5个代谢酶间相互作用特征。结果:分别以1MX1(CES1)、3NXU(CYP450 3A4)、4GQS(CYP450 2C19)、2HI4(CYP450 1A2)、3IBD(CYP450 2B6)为受体,THA、RIT、OXU、Chlorzoxazone、CPZ评价得分为阈值,组方中分别有29、8、31、51、44个化合物分子与代谢酶蛋白CES1、CYP450 3A4、CYP450 2C19、CYP450 1A2、CYP450 2B6间存在一定的结合效应,分析对接的结果与文献cocktail法得出的结论完全一致。结论:复方丹参方可在整体层面上抑制氯吡格雷代谢酶CES1、CYP450 3A4、CYP450 2C19、CYP450 1A2、CYP450 2B6。
OBJECTIVE: To study the effect of compound Danshen dripping pills on human liver carboxylesterase CES1, cytochromes CYP450 3A4, CYP4502C19, CYP450 1A2 and CYP450 2B6 involved in clopidogrel metabolizing enzymes, and to analyze their effects. Methods: Five clopidogrel metabolites-related targets were selected to construct the ligands of chemical constituents of the group, and the computational pharmacological methods were used to explore the interaction between ligand and five metabolic enzymes. Results: The scores of THA, RIT, OXU, Chlorzoxazone and CPZ were respectively evaluated as threshold by 1 CX1 (CES1), 3NXU (CYP450 3A4), 4GQS (CYP450 2C19), 2HI4 (CYP450 1A2) and 3IBD (CYP450 2B6) There were some binding effects between 29,8,31,51,44 compounds and CES1, CYP450 3A4, CYP450 2C19, CYP450 1A2 and CYP450 2B6 respectively in the two groups. The conclusion is exactly the same. Conclusion: Salvia miltiorrhiza can inhibit the clopidogrel metabolizing enzymes CES1, CYP450 3A4, CYP450 2C19, CYP450 1A2 and CYP450 2B6 on the whole level.