葛根素对人肝微粒体中细胞色素P450酶活性的影响  

Effects of Puerarin on the Activities of Cytochrome P450s in Human Microsomes

作　　者：涂自良[1] 张澈[1] 王启斌[1] 程晓莉[1] 张蓬华[1] 

机构地区：[1]郧阳医学院附属太和医院药学部,湖北十堰442000

出　　处：《中国药师》2008年第2期131-134,共4页China Pharmacist

摘　　要：目的:研究葛根素对人肝微粒体中细胞色素P450 1A2(CYP1A2)、CYP3A4、CYP2C9、CYP2C19、CYP2D6、CYP2E1酶活性的影响。方法:分别以咖啡因、咪达唑仑、甲苯磺丁脲、氯唑沙宗、美托洛尔、美芬妥因为探针药,利用HPLC方法测定探针药与相应代谢产物的浓度,研究葛根素在人肝微粒体孵化体系中对CYP1A2、CYP3A4、CYP2C9、CYP2E1、CYP2D6、CYP2C19酶活性的影响。结果:在人肝微粒体反应体系中,0.1,0.2,0.4,0.8 mmol·L^(-1)葛根素使咖啡因的代谢产物的生成分别降低了(31±15)%(P<0.01),(43±8)%(P<0.05),(48±6)%(P<0.05),(49±4)%(P<0.05),0.05,0.1,0.2,0.4,0.8 mmol·L^(-1)葛根素使关托洛尔的代谢产物生成分别降低了(25±7)%(P<0.01),(33±4)%(P<0.05),(40±9)%(P<0.01),(46±5)%(P<0.01),(72±9)%(P<0.01);而对甲苯磺丁脲、美芬妥因、咪达唑仑和氯唑沙宗的代谢产物没有明显影响。结论:在人肝微粒体反应体系中,葛根素(0.1 mmol·L^(-1))对CYP1A2和CYP2D6酶活性有较明显的抑制作用;且随着葛根素浓度的增高,对这两种酶活性的抑制作用也随之增强,而对CYP2C9、CYP2C19、CYP3A4和CYP2E1酶活性没有影响。Objective： To investigate the effects of puerarin on cytochrome P450s （CYPs） activities in human liver microsome in vitro. Method ： Different concentration of caffeine （ the probe drug of CYP1A2）, tolbutamide （ the probe drug of CYP2C9 ）, mephenytoin （ the probe drug of CYP2C19 ） , metoprolol （ the probe drug of CYP2D6 ）, chlorzoxazone （ the probe drug of CYP2E1 ） and midazolam （ the probe drug of CYP3A4） were incubated with or without puemrin in human microsomes respectively. The concentrations of the probe drugs and their metabolites were determined by HPLC, and the cytochrome P450 activities were reflected by the metabolite production. Result： Puerarin （0.1 mmol· L^-1） had no significant effects on the activities of CYP3A4, CYP2C9, CYP2C19, and CYP2E1, but the puerarin concentration of 0.1 mmol · L^-1, 0.2 mmol· L^-1,0.4 mmol · L^-1, 0.8 mmol · L^-1 decreased the activities of CYP1A2 by （31 ± 15）% （P〈0.001）, （43 ±8）% （P〈0.05）, （48 ±6）% （P 〈0.05） and （49 ±4）% （P 〈0.05） respectively, and 0.05 mmol· L^-1 ,0.1 mmol· L^-1 ,0.2 mmol· L^-1 ,0.4 mmol· L^-1,0.8 mmol· L^-1 of puerarin decreased CYP2D6 by （25 ± 7） % （P 〈0.01）, （33±4）%（P〈0.05）,（40±9）%（P〈0.01）, （46±5）%（P〈0.01）and （72±9）%（P〈0.01） respectively. Compared with pre-incubation without puerarin, the metabolites concentration （probe drugs incubated with puerarin） of 4-OH tolbutamide, 4-OH mephenytoin, 6-OH chlorzoxazone and 1-OH midazolam had no statistical differences. Conclusion： Puerarin inhibited the activity of CYP1A2 and CYP2D6 in a dose-dependent fashion in human liver microsome. However, it has no effects on CYP2C9, CYP2C19, CYP3A4 and CYP2E1 in vitro.

关 键 词：葛根素 肝微粒体 细胞色素P450 

分 类 号：R965.1[医药卫生—药理学]