金丝桃苷对人P450同工酶的体外抑制实验及大鼠灌胃给药后尿样中代谢产物的初步分析  

Study on the effect of hyperoside on the inhibition activity of cytochrome P450 enzymes in vitro and analyze the metabolites of hyperoside in urine of rats

作　　者：艾国[1] 刘青川[2] 黄正明[2] 曾勇[3] 刘昌孝[3] 

机构地区：[1]空军航空医学研究所,北京100142 [2]解放军302医院药学部,北京100039 [3]天津药物研究院,天津300193

出　　处：《中华中医药杂志》2015年第10期3705-3708,共4页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金项目(No.30973570);国家中医药管理局新药开发专项(No.DIX005A)~~

摘　　要：目的:研究金丝桃苷对人P450同工酶的体外抑制作用和大鼠灌胃给药后尿样中的代谢产物。方法:采用高通量P450酶抑制剂筛选试剂盒测定了金丝桃苷对P450同工酶CYP1A2、CYP2C9、CYP2C19、CYP2D6和CYP3A4的体外抑制活性。大鼠灌胃给予金丝桃苷(500mg/kg)后收集0-12h内的尿样,经固相萃取法预处理后,采用LC-MS分析尿样,推断代谢产物。结果:金丝桃苷抑制5种P450同工酶的IC50均>10μmol/L。大鼠口服金丝桃苷后,从尿里检测到原型药物和至少9种代谢产物,表明甲基化、硫酸化、葡萄糖醛酸化是金丝桃苷在体内的主要代谢途径。结论:金丝桃苷对5种P450同工酶基本没有抑制作用。金丝桃苷在大鼠体内广泛代谢,形成多种代谢产物。Objective：To study the effect of hyperoside on the inhibition activity of cytochrome P450 enzymes in vitro and analyze the metabolites of hyperoside in urine of rats.Methods：Using P450 high throughput inhibitor screening kit to determine the inhibitory activities of hyperoside to P450 enzymes,CYP1A2,CYP2C9,CYP2C19,CYP2D6 and CYP3A4.Rat urine samples of 0-12 h were collected after ig 500mg/kg hyperoside,then the samples were enriched and purified through solidphase extraction cartridge.Purified samples were analyzed by LC-MS to analyze the metabolites.Results：At 0.009-20μmol/L of hyperoside,the IC50 was over 10μmol/L to five P450 enzymes.Metabolites of hyperoside in the urine were found to have at least nine kinds of metabolic products,included mainly methylation,sulfation and glucuronidation.Conclusion：Hyperoside has no inhibitory action to P450 enzymes（CYP1A2,CYP2C9,CYP2C19,CYP2D6 and CYP3A4）.Hyperoside undergoes extensive metabolic pathways in rats and has many metabolic products.

关 键 词：金丝桃苷 P450同工酶 尿 代谢物 体外抑制 

分 类 号：R285.5[医药卫生—中药学]