针对中药多成分、多途径作用的科学问题，本课题选择既具有药效成分直接作用、又具有肠道菌丛调节作用的大黄为研究载体，探索其改善阿尔兹海默病（AD）认知障碍的药效物质及其多途径作用机制。在前期化学成分、代谢与分布、代谢组学、药效等研究发现大黄改善AD认知障碍存在着多途径作用的基础上，采用人源化大鼠AD模型，结合代谢组、蛋白组分析，构建“化学物质组-作用靶点/效应介质-体内潜在药效物质、验证-中药原型药效成分回溯、验证及多途径作用阐释”为主线的中药药效物质研究模式，从“大黄游离蒽醌类成分直接作用于AD的病理环节及其靶点” 和“苷类成分调控肠道菌丛和肠壁相关受体，改变了内源性活性物质表达量，调控机体炎症反应，改善AD病理环节”双重途径，系统阐释大黄改善人源化大鼠认知障碍的药效物质及其作用机制，为大黄临床治疗AD提供科学依据，并为中药药效物质及其作用机制研究提供新思路，具有重要的学术价值和科学意义。

To solve the scientific problems of multi components and multi pathways of traditional Chinese Medicine, this project choses rhubarb which has direct action of active components and the regulation of intestinal flora, as research carrier, exploring effective substance of the rhubarb improving Alzheimer's disease (AD) cognitive impairment and the mechanism of its multi pathways. Based on the accomplishment of chemical composition, metabolism and distribution, metabolomics and drug efficacy in the early stage finding the multi pathways of rhubarb improving AD cognitive impairment, this project intends to establish the AD model in humanized rat, combine of metabolomics and proteomics analysis, establish drug chemical group analysis- intestinal flora- potential drug substances and their distribution in vivo- drug targets / acting medium- drug derived active components in vivo- retrospective and validation of the prototype of the traditional Chinese Medicine-multi pathway interpretation, providing a reference model for study on the basis of TCM. Based on the dual approach between pathological process and the target of the direct effect of free anthraquinones on AD and rhubarb glycosides regulate of intestinal flora and intestinal wall related receptors, generating endogenous active substances, improving the AD pathological, this project systematic interpretates of rhubarb improving source pharmacodynamic action and mechanism of cognitive impairment in humanized rats, which provides scientific basis for clinical treatment of rhubarb, meanwhile it has an important academic value and scientific significance to provide a new idea for the study of the effective substance and mechanism of TCM.