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欧前胡素(IM)和异欧前胡素(ISOIM)是伞形科常用中药的主要有效成分,在临床上广泛应用。该文研究了IM和ISOIM对人和大鼠肝微粒体细胞色素P450酶(CYP)活性的抑制作用,并评价它们的相互作用潜能。在体外将系列浓度的IM和ISOIM与人和大鼠肝微粒体孵育30 min,以非那西丁、安非他酮、甲苯磺丁脲、S-美芬妥英、右美沙芬和咪达唑仑为CYP探针底物,应用LC-MS/MS定量检测各探针底物的代谢产物生成量,计算得到的IC50,评价两药对人肝CYP1A2,2B6,2C9,2C19,2D6,3A4酶,以及大鼠肝CYP1A2,2B6,2D2,3A1/2酶的抑制活性,并对抑制强度进行分级。在人肝微粒体中,IM和ISOIM对6个CYP同工酶均有不同程度的抑制作用。它们是1A2和2B6的强抑制剂,抑制1A2的IC50分别为0.05,0.20μmol.L-1;抑制2B6的IC50分别为0.18,1.07μmol.L-1。两药还是2C19的中等抑制剂,以及2C9,2D6,3A4的弱抑制剂。在大鼠肝微粒体中,IM和ISOIM是1A2的中等抑制剂,IC50分别为1.95,2.98μmol.L-1。它们分别是2B6的中等和弱抑制剂,IC50为6.22,21.71μmol.L-1。两药还是2D2,3A1/2的弱抑制剂。结果表明IM,ISOIM对人肝CYP酶有广泛的抑制作用,它们是CYP1A2和2B6酶的强抑制剂,临床用药时应注意因CYP酶抑制引起的相互作用。
Imperatorin (IM) and isoimperatorin (ISOIM) are the main active ingredients commonly used in traditional Chinese medicine of Umbelliferae and are widely used clinically. This article studies the inhibitory effects of IM and ISOIM on human and rat liver microsomal cytochrome P450 enzymes (CYP) activity and their potential for interaction. Serial in vitro concentrations of IM and ISOIM were incubated with human and rat liver microsomes for 30 min with phenacetin, bupropion, tolbutamide, S-mephenytoin, dextromethorphan and mida Azolam CYP probe substrate, the use of LC-MS / MS quantitative detection of each probe substrate metabolite production, calculated IC50, evaluation of two drugs on human liver CYP1A2, 2B6, 2C9, 2C19, 2D6, 3A4 Enzyme, and rat liver CYP1A2,2B6,2D2,3A1 / 2 enzyme inhibitory activity, and to suppress the intensity of grading. In human liver microsomes, IM and ISOIM had different degrees of inhibition on six CYP isoenzymes. They are strong inhibitors of 1A2 and 2B6 with IC50 of 0.05 and 0.20 μmol.L-1, respectively, for 1A2 and IC50 of 0.18 and 1.70 μmol·L-1, respectively. The two drugs are also moderate inhibitors of 2C19, and 2C9, 2D6, 3A weak inhibitors. In rat liver microsomes, IM and ISOIM are moderate inhibitors of 1A2 with IC50 of 1.95 and 2.98 μmol.L-1, respectively. They are moderate and weak inhibitors of 2B6 with IC50 of 6.22 and 21.71 μmol.L-1, respectively. Two drugs or 2D2,3A1 / 2 weak inhibitor. The results showed that IM and ISOIM have a wide range of inhibitory effects on human liver CYP enzymes. They are strong inhibitors of CYP1A2 and 2B6 enzymes. In clinical practice, attention should be paid to the interaction caused by CYP enzyme inhibition.