Cocktail探针药物法评价灯盏乙素及其苷元对大鼠细胞色素P450酶的影响  

In vitro Evaluation of Effects of Scutellarin and Scutellarein on Cytochrome P450 Enzymes by Cocktail Probe Drugs in Rats

作　　者：王静娴[1] 陆苑[1] 黄勇[1,2] 董永喜[1,2] 兰燕宇[1,2] 

机构地区：[1]贵阳医学院药学院,民族药与中药开发应用教育部工程研究中心,贵州贵阳550004 [2]贵州省药物制剂重点实验室,贵州贵阳550004

出　　处：《中国医药工业杂志》2014年第3期261-264,共4页Chinese Journal of Pharmaceuticals

基　　金：国家自然科学基金项目(81060359);贵州省中药现代化科技产业专项项目(黔科合中药字[2011]5029号);贵州省教育厅省长基金(黔省专合字[2011]50号);贵州省中药现代化科技产业研究开发专项(黔科合中药字[2011]5081号)

摘　　要：通过cocktail探针药物法考察灯盏乙素及其苷元体外对大鼠细胞色素P450 （CYP450）酶的影响.采用UPLC-MS/MS法定量测定孵育体系中的灯盏乙素和灯盏乙素苷元;加入不同的辅助因子,考察灯盏乙素的代谢机制;以非那西丁、奥美拉唑、双氯芬酸、睾酮和右美沙芬为探针药,UPLC-MS/MS法测定混合探针药物的浓度,研究灯盏乙素及其苷元在体外孵育体系中对CYP1A2、CYP2C 19、CYP2C9、CYP3A4和CYP2D6酶活性的影响.灯盏乙素在体外肝微粒体中主要代谢为灯盏乙素苷元;NADPH和NADH对灯盏乙素的代谢基本无影响;灯盏乙素对5种主要亚型酶IC50值均大于50μmol/L,灯盏乙素苷元对CYP1A2、CYP2C 19、CYP2C9和CYP2D6酶的IC50值均为10～50 μmol/L.表明灯盏乙素苷元对这4种酶有弱抑制作用,在与经由上述酶代谢的药物合用时,可能会产生药物相互作用.The inhibitory effects of scutellarin and scutellarein on rat cytochrome P450 （CYP450） enzymes were evaluated by cocktail probe drugs. A UPLC-MS/MS method was used for the determination of scutellarin and scutellarein in the incubation system. The metabolic mechanism of scutellarin was also investigated by adding different cofactors. Phenacetin, omeprazole, diclofenac, testosterone and dextromethorphan were chosen as the probe substrates and were determined by UPLC-MS/MS. The influences of scutellarin and scutellarein on the enzyme activities of CYP1A2, CYP2C19, CYP2C9, CYP3A4 and CYP2D6 were also analyzed in vitro. The main metabolite of scutellarin was scutellarein in the liver microsomes. The results showed that NADPH and NADH had no effect on the metabolism of scutellarin. The IC50 values of scutellarin to them were all above 50 μmol/L. However, scutellarein showed weak inhibitory effect on CYP1A2, CYP2C19, CYP2C9 and CYP2D6, with IC50 values of 10 - 50 μmol/L, suggesting that scutellarein could interact with some drugs metabolized by the above four enzymes.

关 键 词：灯盏乙素 灯盏乙素苷元 超高效液相色谱串联质谱法 细胞色素P450酶 COCKTAIL探针药物法 

分 类 号：R285.5[医药卫生—中药学]