目的 基于网络药理学及分子对接技术预测牛膝防治阿尔茨海默病（Alzheimer's disease，AD）的主要活性成分及作用靶点，探讨其"多成分-多靶点-多通路"的作用机制。方法 收集DrugBank和文献报道中AD的治疗靶点，依据中药系统药理学技术平台（TCMSP）构建牛膝的化学成分库；运用Discovery Studio 3.5软件进行分子对接，虚拟筛选牛膝中与AD的靶点结合的化学成分集；通过KEGG数据库对虚拟筛选到的关键靶点进行通路富集分析，采用Cytoscape 3.2.1软件构建牛膝的"成分-靶点-通路"网络。结果 从牛膝中筛选出58个化合物，多为小分子烷烃、酯类和羧酸类化合物，其次为黄酮类、蒽醌类等。这些有效成分可能通过调节CaMK-Ⅱα、CaMK-Ⅱβ、CaMK-Ⅱγ、Akt1和TNF-α等36个AD发病机制的潜在靶蛋白而发挥作用，涉及MAPK signaling pathway、Wnt signaling pathway等12条通路。结论 牛膝中黄酮类、蒽醌类等活性成分可能是其治疗AD的物质基础，其作用机制涉及抗炎、抗细胞凋亡等。

Objective This study was designed to predict the main targets of Alzheimer's disease (AD) in Achyranthis Bidentatae Radix based on network pharmacology and molecular docking methods,and to explore its "multi-component,multi-target,and multi-pathway" mechanism.Methods According to the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP),the library of chemical constituents of Achyranthis Bidentatae Radix was established by referring to Chinese and foreign literature reports and collecting targets for treating AD in DrugBank.The Discovery Studio 3.5 software was used to carry out molecular docking,virtual screening of the chemical composition set of Achyranthis Bidentatae Radix combined with AD target,and KEGG database was used to enrich and analyze the key target of virtual screening.The active compounds of Achyranthis Bidentatae Radix with anti-AD activities were yielded to Discovery Studio 3.5 software and molecular docking to predict the poteneial proteins and carry out related KEGG pathways notation separately.Finally,the network of "active compound-target proteins-pathway" was built and analyzed using the Cytoscape 3.2.1 software.Results The 58 active compounds were selected from Achyranthis Bidentatae Radix,of which were mostly small alkanes,esters,and carboxylic acids followed by flavonoids and terpenoids.These active ingredients may regulate 36 potential target proteins such as CaMK-Ⅱα,CaMK-Ⅱβ,CaMK-Ⅱγ,Akt1,and TNF-α to play a role in the pathogenesis of AD.The results also suggested that 12 signaling pathways were involved in the pathogenesis of AD,such as MAPK signaling pathway,Wnt signaling pathways and so on.Conclusion This research method initially revealed that the active ingredients of flavonoids and glycosides in Achyranthis Bidentatae Radix are the material basis for the treatment of AD.Its mechanism of action involved anti-inflammatory,anti-apoptosis and so on.

国家自然科学基金资助项目（81660713）；名贵中药资源可持续利用能力建设项目（2060302）；江西省中药学高水平学科国拔经费课题子课题项目（074973）