口服黄芩素对大鼠药物代谢酶的影响

Drug interaction potential of oral baicalein on metabolic enzymes in rats

目的:考察口服黄芩素对大鼠肝细胞色素P450(CYP450)、谷胱甘肽-S-转移酶(GST)和尿苷二磷酸-葡萄糖醛酸转移酶(UGT)活性的影响。方法:大鼠连续7 d口服200 mg.kg-1黄芩素后,差速离心法制备肝微粒体和肝胞浆,采用特异性探针底物法测定肝微粒体CYP450酶系6种同工酶活性的变化,采用比色法检测GST和UGT活性的变化。结果:大鼠口服黄芩素对CYP2C9,CYP2E1,GST和UGT有显著的抑制作用,抑制率分别为26.76%,29.12%,37.45%和70.86%(P<0.05或0.01),对CYP1A2,CYP2C19,CYP2D6和CYP3A4没有明显的影响。结论:其他药物与黄芩素合用时,需考虑可能由于代谢酶活性变化引起的药物相互作用。

Objective： To study the interaction potential of oral baicalein on main metabolic enzymes, including six hepatic CYP450 isoforms, GST and UGT. Methods： Hepatic microsomes and cytoplasm were prepared by a differential centrifugation method after oral administration of baicalein at 200 mg·kg^-1 for 7 days in rats. Specific substrates were used as probes of six CYP450 isoforms to describe the activities of CYP450 isoforms. The ac- tivities of GST and UGT were detected by a colorimetric method. Results： Repeated dosing of baicalein showed a significant inhibition of CYP2C9, CYP2E1, GST and UGT in 37.45% and 70.86% （P 〈0.05 or 0.01）, respectively. CYP2C19, CYP2D6 and CYP3A4 were observed. Conclusion zymes indicates that potential drug-drug interaction may occur rats. The inhibition rates were 26.76% , 29.12% , No significant effects on the activities of CYP1A2, ： The inhibition of baicalein on several metabolic enwhen baicalein administered with other drugs