厚朴酚与和厚朴酚对药物代谢酶CYP2C19活性影响

EFFECT OF MAGNOLOL AND HONOKIOL ON THE ACTIVITY OF THE DRUG-METABOLIZING ENZYME CYP2C19

目的了解厚朴的主要成分厚朴酚与和厚朴酚对人体最主要的药物代谢酶CYP2C19活性的抑制作用,以预测中药-药物相互作用可能性。方法采用肝微粒体孵育法,以奥美拉唑为CYP2C19的活性探针药物,采用液相色谱-质谱联用法测定代谢产物5-羟基奥美拉唑的浓度,计算代谢产物的初始生成速率,比较加入不同浓度的厚朴酚、和厚朴酚或空白溶剂(pH值7.4磷酸盐缓冲液)时代谢产物的初始生成速率。结果厚朴酚与和厚朴酚对CYP2C19抑制作用的IC50值分别为0.527μmol/L和0.841μmol/L,抑制常数(Ki)分别为0.449μmol/L和0.702μmol/L,厚朴酚与和厚朴酚对CYP2C19抑制作用类型均为非竞争性抑制。结论厚朴中厚朴酚与和厚朴酚均对CYP2C19活性有明显的抑制作用,可能导致药物相互作用。

Objective To investigate the inhibitory effect of magnolol and honokiol,the main constituents of Magnolia officinalis,on the catalytic activities of the most important drug-metabolizing enzyme CYP2C19 in human body,and to predict the possibility of traditional Chinese medicine-drug interaction.Methods The method of liver microsomal incubation was used,and with omeprazole as the substrate of CYP2C19,liquid chromatography-mass spectrometry was used to measure the concentration of the metabolite5′-hydroxyomeprazole.The formation velocities of5′-hydroxyomeprazole were calculated after the addition of various concentrations of magnolol or honokiol or the blank solvent phosphate buffered saline(pH7.4).Results Magnolol and honokiol showed noncompetitive inhibitory effects on CYP2C19 with IC50values of 0.527μmol/L and0.841μmol/L,respectively,and the Ki values were0.449μmol/L and0.702μmol/L,respectively.ConclusionBoth magnolol and honokiol in Magnolia officinalis have a marked inhibitory effect on CYP2C19 and may induce drug-drug interaction.