药物ADME研究是新药研发的重要内容，对揭示药物体内的药效物质和毒性物质具有很好的指导意义。中药由于其成分复杂多样，如何高效的开展中药的ADME研究，是体内药物分析学家一直关注的热点和难点。申请人前期在国家自然科学基金青年科学基金的资助下，初步构建了一种基于多种HRMS/MSn数据集挖掘技术研究中药入体成分ADME全过程的策略。本项目拟在此基础上，利用可作为药物高通量筛选的斑马鱼为模式动物，以中药治疗糖尿病（消渴病）的经典复方和中成药为研究对象，综合运用质谱数据集挖掘技术、多元信息统计处理等研究方法，构建全新、高效的中药降糖药效物质（群）快速筛选体系。采用计算机辅助找靶结合代谢组学、蛋白质组学以及系统生物学等相关技术，研究药效物质（群）作用的分子机制。项目的成功实施，将为研究中药药效物质基础和寻找中药来源的活性先导化合物提供分析技术支撑和研究模式的参考。

ADME studies, an essential part of drug discovery, play a fundamental constructive role in the exploration of in vivo effective and toxic substances in drugs. How to study ADME process of complex systems such as Traditional Chinese Medicine (TCM) in a high-throughput manner remains a challenge in biopharmaceutical analysis. Funded previously by National Scientific Fund for Young Scientists, the applicant has formulated a preliminary integrated approach for studying Absorption, Distribution, Metabolism and Excretion, (ADME) based on multiple HRMS/MSn dataset mining techniques. In this work a high-throughput screening platform for drug discovery in zebra fish will be developed for the study of classic compound prescriptions and Chinese patent medicines used in the treatment of Diabetes. MS dataset mining techniques, multi-information statistical treatment and other methods will be integrated to construct a brand new, high performance rapid screening system for the screening of antidiabetic substances (group) from TCM. Computer aided target fishing combined with metabonomics, proteomics, systematic biology and other related techniques will be applied to study the molecular mechanism of active substances (group). The success of this project will provide an analysis technical support and research pattern reference for the study of pharmacodynamic material basis of TCM and the discovery of active lead compounds from TCM.