阿尔茨海默病（AD）发病率高、危害大，尚无有效治疗手段。补肾是中医治疗AD之首选方法，现代研究表明雌激素抗AD作用明确，而补肾中药含有大量植物雌激素成分能够选择性激活雌激素受体（ERs）产生雌激素效应。据此，我们提出“植物雌激素成分通过中枢性雌激素/受体靶点效应产生神经元保护作用，是补肾中药抗AD的药效物质”之假说。以补肾中药骨碎补、杜仲和补骨脂为研究对象，从中快速筛选植物雌激素成分组/单体，分析其体内（血和脑）转运能力和动力学特点，然后作用于APP和SAMP8小鼠AD模型以及原代神经元细胞AD模型，以调控学习记忆相关中枢ER信号转导通路为核心作用靶标，兼顾整体雌激素效应，从“活性成分-入脑-ER受体-AD病理因子”层面，结合代谢组学和网络药理方法，深入阐明补肾中药所含植物雌激素成分抗AD的有效性和作用机理，为抗AD受体靶点药物开发提供候选成分，为补肾中药治疗AD的药效物质研究提供新思路。

Alzheimer's disease (AD) is a degenerating disease of the brain, accompanied by the loss of cortical nerve cells and resulting in severe atrophy of the frontal, temporal and parietal cortical areas and eventually the death of the patient, which tends to become more epidemic recently. Clinically, kidney-invigorating is a usual and efficient way to therapy AD. And phytoestrogens commonly exsiting in kidney-invigorating herbs showed efficient effects to improve AD by estrogen receptors (ER) pathways. Therefore, the estrogens/ER dependent mechanism on related nervus centralis of phytoestrogens from Drynaria Rhizome, Eucommia Ulmoides and Fructus Psoraleae will be studied in this project. The pharmacokinetics and brain distribution of active phytoestrogens are characterized. With APP and SMP8 mice as animal model and cultured neuronal centralis as cell model, the estronic activities in vivo and ER siganl pathways on target cortical nerve are evaluated. Futher studies of differentiated endogenous metabolites and related biological basis of ER pathways are explored by metabonomics method and Network pharmacology technology. This project will explore the activities and mechanisms of phytoestrogens against AD and provide a new research strategy for anti-AD constituents from kidney-invigorating herbs.