基于质谱技术的“体外-体内”多维化学物质组逐层递进关联分析策略用于中药体内药效物质基础研究

中药药效物质基础研究是中药研究的核心科学问题之一。然而，由于中药成分繁多、体内作用过程复杂且药源性成分浓度低等特点，给中药药效物质基础研究带来了极大的困难和挑战。本文基于口服中药 进入体内主要通过肠道代谢吸收，且进入体内后会在肝脏进一步代谢的特点，提出“体外-体内”多维化学物质 组逐层递进关联分析研究策略，逐步分解药源性成分检测难度，增强药源性成分分析的靶向性；并构建基于靶 向网络药理学方法的体内药效物质组快速辨识方法，无需分离制备单体即可实现体内药效物质组的快速发 现。利用该方法已经阐明了茯苓治疗阿尔兹海默症的药效物质基础。

Studies on the Pharmacodynamic Substance Basis of Traditional Chinese Medicine by Using the Mass Spectrometry-Based Stepwise Targeted Matching Strategy for Analysis of Multidimensional Chemicalome from in Vitro to in Vivo

Study on the pharmacodynamic substance basis of traditional Chinese medicine (TCM) is one of the key scientific problems in the modernization of TCM. However, researches of comprehensive characterization of pharmacodynamic substance basis of TCM faced big challenges because of various components of TCM, the complex in vivo process and low concentration of pharmaceutical ingredients. In this paper, the mass spectrometry-based stepwise targeted matching strategy for analysis of multidimensional chemicalome from in vitro to in vivo was proposed because all metabolites were transformed gradually by using various functional enzymes in different tissues or organs, and because the drugs which taken orally would be exposed to different tissues or organs orderly. This strategy could gradually decompose the difficulty of detecting drug components and enhance the targeting of pharmaceutical ingredients analysis. Moreover, the targeted network pharmacology method was constructed to rapid discovery of the in vivo pharmacodynamic substance basis of TCM without the need to separate the monomeric compound. The pharmacodynamic substance basis of Poria cocos on treating Alzheimer''s disease has been elucidated using this method.