在中药现代化研发和临床应用中，需要对药物相互作用进行安全性评价，而HDI主要是由CYP450介导的。cocktail模型能在单个体系中同时获得多个亚型的信息，然而该法很少用于中药研究，且模型主要利用肝微粒体，多为4到6种的亚型组合，和体内代谢最为接近的原代肝细胞则没有相应模型建立；研究主要集中在酶活性的变化，对mRNA、蛋白质影响以及转录调控因子核受体的机制研究不足。申请者已成功建立了6种亚型的肝微粒体模型，在此基础上本课题将分别构建8种亚型组合的肝微粒体和原代肝细胞cocktail模型，利用LC/MS/MS、RT-PCR及Western blot等技术研究酶活性、mRNA、蛋白质、PXR、CAR、AhR的变化，明确作用发生的层次和机制。并以银杏叶提取物为例进行验证，对单体同系物进行高通量筛选和构效研究。课题的完成对于研究中药的DDI，安全合理应用，促进中药现代化具有重要理论和现实意义。

Concomitant use of herbal and Western medicines is increasing worldwide, thereby increasing the possibility of clinically significant herb-drug interactions which were mainly mediated by cytochrome P450 enzymes. Major hepatic CYP450 isozymes can be simultaneously examined by incubation in human liver microsomes with a cocktail of multiple specific probes, but this strategy is seldom used for the research of herb. Human hepatocytes, a intact cell systems, with full complements of enzymes and cofactors at physiological levels and natural orientations, should be more representative of the liver in vivo than cell-free systems with disrupted membranes and incomplete cofactors and enzymes. but the cocktail model with human hepatocytes was rare. The studies always focused on the enzyme activities, not mRNA, protein and nuclear receptors which regulate gene expression. In this research, we will develop the cocktail model with a mixture of eight probes using human liver microsomes and hepatocytes respectively, to study the activities, mRNA, protein of enzymes and the expression of PXR, CAR, AhR using LC/MS/MS, RT-PCR and Western blot technique. And then study the interaction and mechanisms between Ginkgo biloba extract and cytochrome p450, as well as the structure-function relationships of active constituents homolog. These cocktail models are useful for evaluating the herb-drug interaction, promoting the rational use of herb and the modernization herb discovery and development process .