目的 基于网络药理学和分子对接技术探讨文冠果壳苷治疗阿尔茨海默病的潜在靶点和作用机制。方法 通过对中英文数据库进行文献检索发现，文冠果壳苷具有较好的抗阿尔茨海默病生物活性。利用药物、靶点网络分析、蛋白相互作用（PPI）分析、基因本体（GO）和京都基因和基因组百科全书（KEGG）富集分析确定文冠果壳苷在阿尔茨海默病中的潜在靶点和信号通路。通过AutoDock Vina进行药物与靶点蛋白的分子对接。结果 在对220个药物靶点和1 724个疾病靶点进行交叉筛选后，得到99个核心靶点，主要富集在磷脂酰肌醇-3-激酶（PI3K）/蛋白激酶B1（Akt）信号通路和表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKI）耐药途径，其中成纤维细胞生长因子2（FGF2）、胰岛素样生长因子1（IGF1）、热休克蛋白90α家族A类成员1（HSP90AA1）蛋白与文冠果壳苷亲和力较好。结论 文冠果壳苷可能通过FGF2、IGF1、HSP90蛋白调节PI3K/Akt信号通路和EGFR-TKI耐药途径发挥神经保护作用，为文冠果壳苷在防治阿尔茨海默病中的机制研究提供了新方向。

Objective To investigate the neuroprotective effect of xanthoceraside and its potential targets and mechanisms in Alzheimer's disease. Methods Through literature search of both Chinese and English databases, it was found that the xanthoceraside had good biological activity against Alzheimer's disease. Using drug, target network analysis, PPI analysis, GO and KEGG enrichment analysis, the potential targets and signaling pathways of xanthoceraside in Alzheimer's disease were determined. Molecular docking between the drug and the target protein was conducted using AutoDock Vina. Results After cross-screening 220 drug targets and 1 724 disease targets, 99 core targets were obtained, mainly enriched in the PI3K/Akt signaling pathway and the EGFR-TKI resistance pathway. Among them, FGF2, IGF1, and HSP90AA1 proteins had good affinity with the xanthoceraside. Conclusion Xanthoceraside may exert its neuroprotective effects by regulating the PI3K/Akt and EGFR tyrosine kinase-related signaling pathways through FGF2, IGF1, and HSP90 proteins, which provides new directions for research into the mechanisms of xanthoceraside in the prevention and treatment of Alzheimer's disease.

沈阳医学院硕士研究生科技创新基金项目（Y20240517）