加味佛手散胶囊对大鼠和人肝微粒体CYP450酶活性的抑制作用  

In vitro inhibitory effects of Jiawei Foshou San capsule on activity of cytochrome P450 enzymes in rat and human liver microsomes

作　　者：尚芳红[1,2] 俸珊[1] 陈乾[1] 陈先进[1] 张继芬[1] 徐晓玉[1] 

机构地区：[1]西南大学药学院.中医药学院,重庆400715 [2]重庆市中药研究院,重庆400065

出　　处：《药学学报》2016年第6期926-930,共5页Acta Pharmaceutica Sinica

基　　金：国家重大新药创制专项(2014ZX09304-306-04);重庆市科委科技创新能力建设项(2010GC0035)

摘　　要：考察加味佛手散胶囊及其组分对大鼠和人肝微粒体CYP1A2、CYP2C9、CYP2D6(大鼠2D2)、CYP2E1及CYP3A4(大鼠3A1/2)亚酶活性的抑制作用。采用肝微粒体体外孵育"鸡尾酒"法,设阴性对照组、阳性抑制剂对照组、阿魏酸组、川芎嗪组、延胡索乙素组和加味佛手散胶囊组。利用LC-MS/MS法测定代谢产物生成量,计算得到IC_(50),评价加味佛手散胶囊及其组分对大鼠和人肝微粒体5种CYP450酶的抑制活性。阿魏酸和川芎嗪对大鼠和人肝微粒体5种CYP450的IC_(50)未测出。延胡索乙素抑制大鼠肝微粒体CYP3A1/2和人肝微粒体CYP2D6的IC_(50)分别为7.46和9.24μmol·L^(-1)。加味佛手散胶囊抑制大鼠肝微粒体CYP2D2、CYP2E1、CYP3A1/2的IC_(50)分别为241.3、369.8和293.0 mg·L^(-1),抑制人肝微粒体CYP2D6、CYP2E1、CYP3A4的IC_(50)分别为123.9、189.9和171.3 mg·L^(-1)。提示阿魏酸和川芎嗪对大鼠和人肝5种CYP450产生酶抑制的可能性很小;延胡索乙素是大鼠肝CYP3A1/2,人肝CYP2D6酶活性的中等强度抑制剂;加味佛手散胶囊对大鼠和人肝CYP2D、CYP2E1、CYP3A酶活性可能有体外抑制作用。加味佛手散胶囊与其他经CYP2D、CYP2E1、CYP3A酶代谢的药物共用时,可能使该药作用效果增强,作用时间延长,联合用药时应适当减少用药剂量。This study was designed to investigate the inhibitory effects of Jiawei Foshou San（JWFSS） capsule in vitro on five major human liver microsomes CYP1A2, CYP2C9, CYP2D6, CYP2E1, CYP3A4, as well as on rat liver microsomes CYP1A2, CYP2C9, CYP2D2, CYP2E1, CYP3A1/2. The test groups included a negative control group, an inhibitor positive control group, an ferulic acid（FA） group, a ligustrazine（LZ） group, a tetrahydropalmatine（THP） group, and an JWFSS capsule group. After incubating the liver microsomes with a cocktail of probe drugs, the metabolites were quantitated with LC-MS/MS, and IC_（50） values were calculated to assess the inhibitory effect of JWFSS capsule and its components on five rat/human CYP450 enzymes. All of the IC_（50） values for the FA and the LZ for the five CYPs could not be determined. The IC_（50） of the THP for rat CYP3A1/2 and for human CYP2D6 was 7.46 and 9.24 μmol·L^（-1）, respectively. The IC_（50） of the JWFSS capsule for rat CYP2D2, CYP2E1 and CYP3A1/2 was 241.3, 369.8 and 293.0 mg·L^（-1）, for human CYP2D6, CYP2E1 and CYP3A4 was 123.9, 189.9 and 171.3 mg·L^（-1） respectively. The results indicated there were little probability that FA and LZ inhibited the activity of rat and human liver five CYPs; THP was identified as moderate-intensity inhibitor of rat liver CYP3A1/2 and human liver CYP2D6; JWFSS capsule might have a inhibitory effect on the activity of rat and human liver CYP2D, CYP2E1 and CYP3A in vitro, showing that there was a strengthened efficacy and a prolonged effective time for drugs metabolized by CYP2D, CYP2E1, CYP3A and combined with JWFSS capsule.

关 键 词：加味佛手散胶囊 子宫内膜异位症 CYP450 肝微粒体 阿魏酸 川芎嗪 延胡索乙素 

分 类 号：R943[医药卫生—药剂学]