目的 基于网络药理学和实验动物模型探讨杜仲对阿尔茨海默病（AD）的作用机制。方法 采用中药系统药理学数据库与分析平台（TCMSP），获取杜仲的主要活性成分，用SwissTargetPrediction收集杜仲活性成分全部作用靶点。从DrugBank、PathCard、Chemogenomic Database和PubChem数据库获取AD靶点。使用韦恩图取交集，得到杜仲治疗AD的共同作用核心靶点。利用Cytoscape 3.8.0构建靶点的“活性成分-核心靶点”网络图。采用Metascape进行基因本体（GO）和京都基因与基因组百科全书（KEGG）富集分析，筛选出杜仲主要作用信号通路。使用CB-DOCK2进行分子对接，并用Pymol和Discovery Studio展示对接结果。通过ip东莨菪碱构建AD小鼠模型，并给予杜仲颗粒ig处理，采用新物体识别实验检测小鼠学习记忆能力，通过免疫荧光检测神经元核抗原抗体（NeuN）的表达。结果 预测得到杜仲的11种主要活性成分，381个作用靶点，674个AD相关靶点，其中杜仲治疗AD共同核心靶点78个。杜仲干预AD可能通过蛋白质磷酸化、细胞凋亡、化学突触传递调节、β淀粉样蛋白代谢过程等，还可能涉及AD、多巴胺能神经元、钙信号通路等。动物实验结果表明，杜仲高剂量有助于改善AD小鼠认知功能障碍，并恢复AD神经元标志物NeuN的表达。结论 杜仲可能通过多成分、多靶点、多通路参与调控AD疾病进程，其机制可能涉及抑制神经元凋亡等。

Objective To investigate the mechanism of Eucommia ulmoides in Alzheimer's disease(AD) based on network pharmacology and experimental animal models. Methods The main active components of E. ulmoides were obtained from the Traditional Chinese Medicine System Pharmacology Database(TCMSP), and all targets were collected using SwissTargetPrediction. AD genes were obtained from the DrugBank, PathCard, Chemogenomic Database, and PubChem databases. Diagrams were used to identify the intersection, yielding core target proteins common to E. ulmoides treatment for AD. Cytoscape 3.8.0 was employed to construct the “active component-core target” network diagram. Metascape was utilized for GO and KEGG enrichment analysis to screen the primary signaling pathways involved in E. ulmoides. Molecular docking was performed using CB-DOCK2, with results visualized via Pymol and Discovery Studio. An AD mouse model was established by ip injection of scopolamine, followed by E. ulmoides oral administration. Learning and memory abilities were assessed through the novel object recognition test, while NeuN expression was detected via immunofluorescence. Results Eleven major active components, 381 target proteins, and 674 AD-related targets were predicted for E. ulmoides, including 78 common core targets for AD treatment. Intervention of E. ulmoides in AD may occur through pathways including protein phosphorylation, apoptosis, chemical synapse transmission regulation, and β-amyloid metabolism, potentially involving AD, dopaminergic neurons, and calcium signaling pathways. Animal studies indicate that high-dose of E. ulmoides improves AD-related cognitive impairment and restores the AD neuronal reduction. Conclusion E. ulmoides may participate in regulating the AD disease process through multiple components, multiple targets, and multiple pathways. Its mechanism may involve neuronal apoptosis, providing scientific basis for systematically elucidating its action mechanism.

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国家自然科学基金资助项目(82301374); 湖北省自然科学基金襄阳联合基金培育项目(2025AFD068); 湖北文理学院大学生创新创业训练计划项目(S202510519064、X202510519115);湖北文理学院神经科学与脑科学研究所开放课题(2023NBI07); 襄阳市中心医院科研启动经费(2024BS03);襄阳市中心医院人才培养经费(2025RCQM-089)