药物对胆红素代谢酶UGT1A1的抑制是引发胆红素代谢障碍和药药相互作用的一个重要原因。部分中草药可通过抑制UGT1A1引发高胆红素血症、肝功能异常及草药-药物相互作用等安全隐患，业界迫切需要构建适于中药等复杂研究对象的UGT1A1抑制剂的高效筛选与精准评价体系。本项目拟在前期工作基础上，借助自主研发的UGT1A1特异性荧光探针底物构建适于复杂生物体系的UGT1A1抑制剂筛选与评价方法，实现从组织制备物→活细胞→活体的多层次系统筛选和精准评价；同时采用中药化学指纹谱和抑制效应谱相结合的策略，构建谱效结合导向下的天然UGT1A1抑制剂的发现与评价体系，并将其用于中药对UGT1A1抑制作用的规模化筛选、天然UGT1A1抑制剂的高效发现及抑制作用的精细表征等研究。该项目有望从技术和理论两个层面提升我国中草药-药物相互作用研究的整体水平，同时为中药方剂的去粗取精及临床合理用药提供科学依据和研究示范。

Inhibition on bilirubin metabolizing enzyme UGT1A1 is one of the most important reason for bilirubin metabolism imbalance and drug-drug interactions. Several Chinese herbs can induce hyperbilirubinemia, liver injury and herb-drug interactions via UGT1A1 inhibition. It is urgently needed to establish a fast and accurate method for rapid screening and characterization of UGT1A1 inhibitor from herbs in both academy and industry. Following our previous works, this project aimed to construct a screening platform for UGT1A1 inhibitors by using our self-developed fluorescence probe substrates for UGT1A1, which could be applied in complex biological systems. The platform will achieve a multi-system screening and precise evaluation of UGT1A1 inhibitors from tissue preparation to live cell and then to living organism. Meanwhile, the fingerprinting techniques combined with bioactivity-based assays will be used to construct a new system for screening and discovery of natural UGT1A1 inhibitors from herbal extract. All these newly developed platforms will be applied in high-throughput screening for UGT1A1 inhibitors from Chinese herbs, as well as screening and characterization for natural UGT1A1 inhibitors. This project is expected to enhance the overall levels of herb-drug interactions associated studies in China from both technical and theoretical aspects. Furthermore, this project will provide a scientific basis and research standard for selecting the essence and discard the dross from the Chinese medicine formula and guiding for rational application of herbs in clinic.