中国临床药学杂志2007,Vol.16Issue(3):133-138,6.
体外细胞色素P450同工酶对银杏叶水提取物抗血小板聚集作用的影响
Effects of cytochrome P450 isozymes from human hepatocytes on inhibition of platelet aggregation induced by Ginkgo extract
摘要
Abstract
AIM To estimate the effects of cytochrome P450 isozymes on efficacy of Ginkgo biloba leaf extract(GBE)-inhibition of platelet aggregation by using cryopreserved human primary hepatocytes (HPHs) in vitro. METHODS Plasma with rich platelets (PRP), plasma with poor platelets (PPP), and HPHs were prepared from donation. Platelet L-1. Effect of GBE on PAF induced platelet aggregation was estimated by preincubaiton of GBE before the addition of PAF. The effects of first pass metabolism on the efficacy of the GBE were investigated by preincubation of HPHs with GBE. The metabolism pathways involved for GBE were identified by preincubation of HPHs with selective inhibitors of CYP1A2 (α-naphthoflavon), CYP2B6 (orphenadrine hydrochlorid), CYP2C19 (omeprazole), CYP2E1 (4-methylpyrazole), and CYP3A4 (itraconazole). RESULTS PAF induced platelet aggregation followed Michaelis-Menten kinetics 30% enhancement over the control. These effects of GBE were reduced significantly by selectively inhibiting CYP1A2 but CYP2B6, 2C19, 2E1 and 3A4. CONCLUSION The inhibitive effects of GBE on PAF induced platelet aggregation are regulated by CYP1A2. The study implies an application for identifying the metabolism pathway of herb medicines in vitro.关键词
银杏叶提取物/血小板活化因子/血小板聚集/细胞色素P450药物代谢同工酶Key words
Ginkgo biloba leaf extract/platelet-activating factor/platelet aggregation/cytochrome P450 isoztmes分类
医药卫生引用本文复制引用
邱东鹰,毛玉昌,乔燕荣,谭金兴,胡卓汉,蔡映云..体外细胞色素P450同工酶对银杏叶水提取物抗血小板聚集作用的影响[J].中国临床药学杂志,2007,16(3):133-138,6.基金项目
This project was supported by the grant of Scientific Foundation for Young Researchers at Fudan University,and the Grant for in vitro drug metabolism and interaction evaluation by the State Ministry of Sciences and Technologies of China (No.03C26213100901). (No.03C26213100901)