基于“结构相似性分类-质谱可视化解析”的甘草制吴茱萸物质基础及减毒机理研究

中药炮制是中医药临床用药的特色，有毒中药经过炮制后可以减毒增效。在前期吴茱萸炮制工艺摸索、炮制前后HPLC液相色谱对比、液相质谱联用考察、结构相似性分类质谱解析方法及肝损伤药理研究基础上，采用超高效液相色谱/气相指纹图谱方法评价吴茱萸不同产地药材属性；基于“结构相似性分类-质谱可视化解析”策略，全谱、非靶向、高效解析液质联用质谱数据，获得体内外物质基础的多维度信息；分离分析毒性-药效作用部分，进行“物-毒-效”关联分析，探究毒性与药效作用的物质基础；结合药理与分子生物学技术手段，探索整体动物-细胞-分子水平毒性和炮制减毒机理，构建吴茱萸炮制前后物质基础-药效毒理-炮制机理综合研究体系，阐释炮制减毒的现代科学意义，阐明甘草制“缓和药性、降低毒性”的科学内涵，为炮制工艺规范、质量标准制定、临床安全合理用药提供科学支持，为有毒中药的安全性评价及毒性效用研究提供新思路。

Process technique is a unique characteristic of Chinese Materia Medica (CMM) applied in clinics, usually toxic CMM can reduce toxicity and remain efficacy through these processing techniques. In our previous researches, we have investigated the processing procedure, HPLC determination before and after process, HPLC-MS identification, structurally similar classification MS data analysis method and preliminary liver injury pathology study of Evodia Fructus. In this project, the plant origins will be investigated by UPLC/GC fingerprint method, mass untargeted MS data will be fully elucidated by "structural similar classification – MS data visualization strategy" and to obtain the multiple dimensions of vitro &vivo bioactive components. “Components-toxicity-efficacy” relations were fully explored, in order to illustrate the underlining relation of toxic and effective components. Biological and molecular techniques, as well as pharmacology method, were developed to explain the toxicity and detoxification principles at whole-cell-molecular levels, and the comprehensive research system was constructed during this procedure. The scientific significance of processing detoxification was addressed, as well as glycyrrhiza reducing toxicity and heat of Evodia Fructus. This project will provide strong supports for the processing practice, quality control, clinical reasonable medication, and may provide a new methodology for the safety evaluation and toxic-effect investigation of toxic CMM.