五味子提取物对大鼠肝CYP3A酶的双重作用  

Dual effects of extract of Schisandra chinensis Baill on rat hepatic CYP3A

作　　者：陈倩[1] 吴育晶[1,2] 程能能[1] 李雅琳[1] 王永铭[1] 

机构地区：[1]复旦大学药学院药理学教研室,上海201203 [2]安徽医科大学临床药理研究所

出　　处：《药学学报》2010年第9期1194-1198,共5页Acta Pharmaceutica Sinica

摘　　要：细胞色素P450酶的抑制和诱导是产生药物相互作用最常见的原因[1,2]。在P450酶中,以CYP3A酶的含量最多,底物也最广泛。研究发现。This study is to investigate the effects of aqueous extract of Schisandra chinensis Baill （WWZ）, kadsurin, schisandrin A, schisandrin B and schisandrol B on rat hepatic CYP3A. Rats received a daily gavage of aqueous extract of WWZ for different times. The livers were harvested after gavage and subjected to microsome preparation. Microsomal CYP3A activity was determined by measuring the amount of the metabolite of testosterone （6β-hydroxytestosterone） with HPLC. Aqueous extract of WWZ, kadsurin and schisandrin A were incubated with microsomes obtained from rat. Microsomal CYP3A activity was determined by HPLC. Primary hepatocytes were separated and extracted from rat, then were treated with aqueous extract of WWZ, schisandrin A, schisandrin B and schisandrol B. Then, the expression of CYP3A1 mRNA was analyzed by RT-PCR. As for the in vivo assay, aqueous extract of WWZ significantly inhibited the enzyme activity of CYP3A after 12 h gavage. The inhibitory effect was converted to inductive effect after 3-day gavage. Aqueous extract of WWZ could induce the enzyme activity of CYP3A after 6-day gavage. Aqueous extract of WWZ and kadsurin showed a dose-dependent inhibition of CYP3A （IC50 of 487.8 μg·mL？1 and 6.2 μmol·L？1, separately）. In rat primary hepatocytes, aqueous extract of WWZ （2.5 mg·mL？1）, schisandrin A （0.1 μmol·L？1）, schisandrin B （0.1 μmol·L？1） and schisandrol B （10 μmol·L？1） increased significantly the expression of CYP3A1 mRNA by 23%, 55%, 42% and 27%, respectively. Aqueous extract of WWZ could show dual effect on the enzyme activity of CYP3A in rat in vivo. Meanwhile, kadsurin showed a dose-dependent inhibition of the enzyme activity of hepatic CYP3A in vitro. And schisandrin A, schisandrin B and schisandrol B showed significant inductive effect on the expression of rat CYP3A1 mRNA.

关 键 词：五味子 五味子甲素 五味子乙素 五味子醇乙 南五味子素 CYP3A 肝微粒体 原代肝细胞 

分 类 号：R285[医药卫生—中药学]