基于化学生物学的中药药效分子的组织分布及作用靶点研究

Chemical biology of traditional Chinese medicine (TCM) could explain the relationship between the core structures of active ingredients in TCM and their target proteins, and then clarify deeply mechanism between active ingredients and body, and the synergistic effect of the active compositions. In this study, we established a platform to discovery tissue distribution and target protein of active ingredients based on positron emission tomography and magnetic capture technology. Arctigenin and andrographolide were selected as anti-inflammatory compounds to explain the tissue distribution and cellular localization. Target and related proteins were separated and identified by magnetic capture and mass spectrometry techniques. Target proteins were screened and evaluated by combining bioinformatics method, such as Kyoto Encyclopedia of Genes and Genomes (KEGG), and other virtual screening techniques. A multidimensional network of active ingredients’ target-signaling pathway- regulatory network was built. In the end, target and related protein were verified by biological techniques. This method provided basis to explain the treatment mechanism of active ingredients in TCM systematically and effectively, and could discovery innovative targets.

中药的化学生物学可以直接阐释中药药效分子的核心结构与其靶标蛋白的作用关系，深层次挖掘中药药效分子与机体的关系，以及各有效成分之间协同增效的关系。本课题基于正电子发射成像和磁性捕获技术，建立了中药药效分子的组织分布和靶点发现平台，分别选择牛蒡子苷元和穿心莲内酯作为实例，展开了药效分子组织分布和作用靶点确证的化学生物学研究，阐明了中药抗炎药效分子的组织分布和细胞定位，利用磁性捕获和质谱解析技术分离鉴定出对应的靶点蛋白及相关蛋白，应用京都基因与基因组百科全书(KEGG)等生物信息学手段结合计算机虚拟筛选技术进行靶点的筛选和评价，构建药效分子的靶点-信号通路-调节网络的多维网络，最终采用生物学手段对相关靶点和通路进行验证，为系统、准确的阐释中药药效分子的治疗机制及创新靶点的发现提供有效的依据。

近年来，化学生物学技术迅猛发展，可以用来研究中药药效分子的核心结构与其靶标蛋白的作用关系，以及各有效成分之间协同增效的关系。本课题基于正电子发射成像和磁性捕获技术，建立了中药药效分子的组织分布和靶点发现平台，分别选择牛蒡子苷元和穿心莲内酯作为实例，展开了药效分子组织分布和作用靶点确证的化学生物学研究，阐明了牛蒡子苷元和穿心莲内酯的组织分布和细胞定位，并利用磁性捕获和质谱解析技术分离鉴定出对应的靶点蛋白及相关蛋白，应用京都基因与基因组百科全书(KEGG)等生物信息学手段结合计算机虚拟筛选技术进行靶点的筛选和评价，构建了药效分子的靶点-信号通路-调节网络的多维网络。