表没食子儿茶素-3-没食子酸酯对细胞色素P450酶活性的影响

EFFECT OF EPIGALLOCATECHIN-3-GALLATE ON THE ACTIVITY OF CYTOCHROME P450

目的研究表没食子儿茶素-3-没食子酸酯(EGCG)对人肝微粒体中细胞色素P450(CYP450)酶活性的影响。方法以未处理的肝微粒体作为阴性对照组,CYP450酶各亚型的特异性抑制剂作为阳性对照组,通过EGCG或特异性抑制剂与探针底物共同孵育,高效液相色谱法定量分析特异性底物的代谢产物,分析EGCG对CYP450酶各亚型活性的影响,并通过统计学分析拟合获得相应的动力学参数。结果与阴性对照组相比,EGCG显著抑制了CYP1A2酶和CYP3A4酶的活性,但抑制作用远小于阳性抑制剂的抑制作用。EGCG对CYP1A2酶和CYP3A4酶的抑制作用受EGCG浓度的影响,IC50值分别为8.69和14.07μmol/L。EGCG能够竞争性抑制CYP1A2酶的活性,而对CYP3A4酶为非竞争性抑制作用。此外,EGCG对CYP3A4酶的抑制作用具有时间依赖性,随着培养时间的延长,抑制作用逐渐增强。结论EGCG可显著抑制CYP1A2酶及CYP3A4酶的活性。因此,在EGCG的应用中应充分考虑可能出现的药物相互作用及潜在风险。

Objective To investigate the effect of epigallocatechin-3-gallate(EGCG)on the activity of cytochrome P450(CYP450)enzyme in human liver microsomes.Methods The untreated human liver microsomes were established as negative control group,and the specific inhibitors of CYP450 subtypes were established as positive control groups.EGCG or specific inhibitors were incubated with the probe substrate,and high-performance liquid chromatography was used for the quantitative analysis of the metabolic products of the specific substrate.The effect of EGCG on the activity of CYP450 subtypes was evaluated and a statistical analysis was performed to obtain the corresponding kinetic parameters.Results Compared with the negative control group,EGCG significantly inhibited the activity of CYP1A2 and CYP3A4 enzymes,with a significantly weaker inhibitory effect than the positive inhibitor.The inhibitory effect of EGCG on CYP1A2 and CYP3A4 was affected by the concentration of EGCG,with an IC50 of 8.69 and 14.07μmol/L,respectively.EGCG showed competitive inhibition of the activity of CYP1A2 and noncompetitive inhibition of CYP3A4.In addition,the inhibitory effect of EGCG on CYP3A4 was time-dependent,and its inhibitory effect on CYP3A4 gradually increased over the time of incubation.Conclusion EGCG significantly inhibits the activity of CYP1A2 or CYP3A4,and therefore,possible drug interactions and potential risks should be considered in the application of EGCG.