丹参中11个活性成分对人肝微粒体细胞色素酶活性的作用研究  

Inhibitory Effects of Eleven Active Components of Salvia miltiorrhiza Bge.Extract on Catalytic Activity of Cytochrome P450 Enzymes in Human Liver Microsomes

作　　者：徐文[1] 王泽霞 刘涛[1] 曹志红[1] 马敏[1] 马霖[1] 

机构地区：[1]青岛大学附属医院药学部,山东青岛266003 [2]诸城市中医医院西药房,山东潍坊262200

出　　处：《中国药学杂志》2015年第7期619-622,共4页Chinese Pharmaceutical Journal

基　　金：青岛市民生计划资助项目(13-1-3-32-nsh)

摘　　要：目的为了更好的预测丹参制剂导致药物相互作用的可能性,考察了丹参中11个活性成分对5种主要药物代谢酶CYP1A2、CYP2C9、CYP2C19、CYP2D6和CYP3A4活性的影响。方法采用人肝微粒体外孵育方法,以非那西丁、甲苯磺丁脲、美芬妥因、氢溴酸右美沙芬和咪达唑仑作为CYP1A2、CYP2C9、CYP2C19、CYP2D6和CYP3A4的探针药物,采用液相色谱-质谱联用检测探针药物代谢产物生成速率,通过与空白组探针药物代谢产物生成速率比较,计算各个成分对这5种酶活性是否产生影响。结果丹参中多个成分对药物代谢酶有抑制作用,尤其是二氢丹参酮Ⅰ对CYP3A4有强抑制作用,IC50值为0.367μmol·L-1。结论二氢丹参酮Ⅰ含量较高的丹参制剂有可能导致药物相互作用,为精准的预测这种作用,有必要对其含量和体内过程进行进一步研究。OBJECTIVE To predict the potential for drug-drug interactions of Salvia miltiorrhiza Bge.preparations with other drugs,the effects of 11 active components of Salvia miltiorrhiza Bge.on the catalytic activities of 5 drug-metabolizing enzymes were assessed.METHODS Human liver microsome incubation experiment was carried out to assay these components on the catalytic activities of these enzymes.Phenacetin,tolbutamide,S-mephenytoin,dextromethorphane and midazolam were used as the substrates of CYP1A2,CYP2C9,CYP2C19,CYP2D6 and CYP3A4,respectively.After the incubation,the metabolite of each substrate was quantified by LC-MS / MS method.The inhibitions of five main drug metabolism enzymes were calculated by comparing the formation velocities of metabolites with or without Salvia miltiorrhiza Bge.component.RESULTS Some components of Salvia miltiorrhiza Bge.showed obvious inhibiton on the catalytic activities of CYPs,especially dihydrotanshinone Ⅰ showed strong inhibiton on CYP3A4 with IC50 value of 0.367 μmol·L^-1.CONCLUSION Salvia miltiorrhiza Bge.preparation with high content of dihydrotanshinone Ⅰ may cause drug-drug interactions.To predict the interaction precisely,the content of dihydrotanshinone Ⅰ as well as its in vivo process need a further study.

关 键 词：丹参 细胞色素P450 抑制 二氢丹参酮Ⅰ 肝微粒体 

分 类 号：R969.1[医药卫生—药理学]