基于内源性代谢物-生物靶分子-活性成分群-生物效应的整体动态关联模式挖掘苦寒中药的药性本质

This project is a further study of the original subject. TCM (Traditional Chinese medicine) nature theory is an important part and the core content of TCM theory system. The nature and taste theory are both the important component of TCM system. Until now, the research on the scientific connotation for the nature of TCM lacks direct integration and correlation analysis based on the combination between organism and drug. Guided by the basic theory and the framework of the evaluation of TCM nature, we focus on typical bitter cold herbs as research carriers. Based on the previous work of our team, by screening the specific pathway on behalf of TCM nature through network pharmacology and metabolomics, this research will investigate the general target of expressing bitter and cold TCM nature in the body and deduce the biological effect. At the same time, by the PK/PD dynamic changes of herb components in vivo after drug administration, the characteristic components representing the TCM nature will be deduced. Finally, by setting up the correlation relationship and correlation strength their between characteristic TCM nature markers and metabolic TCM nature markers, the dynamic connotation of TCM and metabolism substance by drug intervention will be explored. Ultimately, we will build up the evaluation system for bitter cold herbs through the model of “endogenous metabolite-biological target molecules-active component group-biological effect”to reveal the scientific connotation for TCM nature.

本项目是原有课题工作的深化研究。中药药性理论是中医药理论体系的重要组成部分和核心内容。目前对于中药药性科学内涵的研究缺乏对药性各维度的整合性研究和系统性的相关性分析。本研究以中医药理论为指导，以原有工作为基础，继续以典型苦寒中药为研究载体，通过网络药理学筛选代表药性的特异性作用通路，结合代谢组学研究，考察机体表达苦寒药性的共性靶标及其发生的生物学效应；同时分析给药后体内药物成分的PK/PD动态变化，推知代表药性的特征性成分。最终建立苦寒药性特征性成分与药性代谢标志物的关联关系和关联强度，进一步探索中药药性的动态内涵和药物干预的体内代谢实质，搭建基于内源性代谢物-生物靶分子-活性成分群-生物效应的整体动态关联模式的苦寒药性评价模式和评价体系，揭示中药苦寒药性的药性本质。

中药药性理论是中医药理论体系的重要组成部分和核心内容。目前对于中药药性科学内涵的研究缺乏对药性各维度的整合性研究和系统性的相关性分析。本研究以中医药理论为指导，以五味典型苦寒中药为研究对象，通过网络药理学筛选代表性苦寒中药药性的特异性作用靶点和通路，发现了20个关键靶点，其中重要的靶点是PTGS2、PTGS1、SCN5A等。在机体效应评价基础上，开展了代谢组学研究，发现了苦寒中药黄连给药后的硬脂酸、亚油酸、棕榈酸、二十二碳六烯酸等多个差异代谢物，其中异柠檬酸等四个代谢物呈现下降趋势，其余均为上调趋势，表明黄连主要通过调节上述差异代谢物含量，对机体的能量代谢过程发挥了调节作用。苦寒中药黄连给药后体内成分研究显示，大鼠灌胃给予黄连1.5h后的血清样品中药物原型成分和代谢物多，灌胃2-4h后尿液样品中代谢物丰富；黄连含药血清中出现了12个原型成分，含药尿液中出现了16个原型成分；血液和尿液中黄连吸收成分主要为黄连生物碱类；除木兰花碱外，黄连中生物碱主要为异喹啉生物碱。总结黄柏各类化学成分裂解规律，鉴定或推断了35个化合物，按结构类别主要包括生物碱类、柠檬苦素类、酚酸类和苯丙素类化合物。