In Vitro Oxidative Metabolism of Cajaninstilbene Acid by Human Liver Microsomes and Hepatocytes: Involvement of Cytochrome P450 Reaction Phenotyping, Inhibition, and Induction Studies

文献类型： 外文期刊

第一作者： Hua, Xin

作者： Hua, Xin;Peng, Xiao;Tan, Shengnan;Li, Chunying;Wang, Wei;Luo, Meng;Fu, Yujie;Zu, Yuangang;Peng, Xiao;Li, Chunying;Wang, Wei;Luo, Meng;Fu, Yujie;Hua, Xin;Smyth, Hugh

作者机构：

关键词： cajaninstilbene acid;human liver microsomes;recombinant human P4S0 enzymes;human hepatocytes;food—drug interaction

期刊名称：JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY （ 影响因子：5.279； 五年影响因子：5.269 ）

ISSN：

年卷期：

页码：

收录情况： SCI

摘要： Cajaninstilbene add (CSA, 3-hydroxy-4-prenyl-5-methoxystilbehe-2-carboxylic add), an active constituent of pigeonpea leaves, an important tropical crop, is known for its clinical effects in the treatment of diabetes, hepatitis, and measles and its potential antitumor effect. In; this study, the effect of the cytochrome P450 isozymes on the activity of CSA was investigated. Two hydroxylation metabolites were identified in the study. The reaction phenotype study showed that CYP3A4, CYP2C9, and CYP1A2 were the major cytochrome P450 isozymes in the metabolism of CSA. The metabolic food—drug interaction potential was also evaluated in vitro. The effect of CSA inhibition/induction of enzymatic activities of seven drug-metabolizing CYP4S0 isozymes in vitro was estimated by high-performance liquid chromatography and liquid chromatography— tandem mass spectrometry analytical techniques. CSA showed different inhibitory effects on different isozymes. CSA reversibly inhibited CYP3A4 and CYP2C9 activities in human liver microsomes with IC_(50) values of 28.3 and 31.3 μM, respectively, but exhibited no inhibition activities to CYP1A2, CYP2A6, CYP2C19, CYP2D6, and CYP2EL CSA showed a weak effect on CYP450 enzymes in a time-dependent manner. CSA did not substantially induce CYP1A2, CYP2A6, CYP2B6, CYP2E1, CYP2C9, CYP2C19, CYP2D6, or CYP3A4 at concentrations up to 30 μM in primary human hepatocytes. The results of our experiments may be helpful to predict clinically significant food—drug interactions when other drugs are administered in combination with CSA

分类号： R15`S

  • 相关文献
作者其他论文 更多>>

微信小程序