目的 基于网络药理学及体外实验研究毛兰素治疗阿尔茨海默病的潜在分子作用机制。方法 首先通过检索PubChem、SwissTargetPrediction、citexs数据库，获取毛兰素的作用靶点，后利用TTD、PharmGKB、GeneCards、OMIM、GEO、DisGeNET、Celt平台检索阿尔茨海默病的相关靶点，利用Venny平台、STRING数据库、Cytoscape软件进行拓扑分析获取毛兰素治疗阿尔茨海默病的核心靶点，利用R语言对所获得的交集靶点进行基因本体（GO）功能和京都基因和基因百科全书（KEGG）信号通路富集分析，通过CB-dock2网站进行分子对接，细胞实验进行验证。结果 毛兰素治疗阿尔茨海默病的核心靶点为蛋白激酶B1（Akt1）、B细胞淋巴瘤/白血病-2（Bcl-2）、哺乳动物雷帕霉素靶蛋白（mTOR）。GO富集分析显示与神经元凋亡相关，KEGG通路富集分析得到关键通路为磷脂酰肌醇-3-激酶（PI3K）/Akt信号通路。分子对接结果显示毛兰素与3个核心靶点均具有较好的结合能力。细胞实验结果表明，与模型组比较，毛兰素组SH-SY5Y细胞活性显著增高，细胞凋亡程度下降（P＜0.01），且毛兰素浓度为50 nmol/L时细胞活力最高；经毛兰素干预后，SH-SY5Y细胞mTOR、细胞凋亡调节因子（Bax）蛋白表达显著降低；Bcl-2、p-Akt、Akt、PI3K蛋白表达显著升高（P＜0.001）。结论 毛兰素可能通过调控PI3K/Akt信号通路抑制细胞凋亡，对阿尔茨海默症起到潜在治疗效果。

Objective To explore the potential molecular mechanisms of erianin in treatment of Alzheimer's disease based on network pharmacology and in vitro experiments. Methods The targets of erianin were obtained by searching databases such as PubChem, SwissTargetPrediction, and citexs. The relevant targets of Alzheimer's disease were retrieved from databases including TTD, PharmGKB, GeneCards, OMIM, GEO, DisGeNET, and Celt platform. Topological analysis was carried out using Venny platform, STRING database, and Cytoscape software to obtain the core targets of erianin in treatment of Alzheimer's disease. GO functional and KEGG pathway enrichment analyses were performed on the obtained intersection targets using R language. Molecular docking was conducted via the CB-dock2 website, and cell experiments were carried out for verification. Results The core targets of erianin in treatment of Alzheimer's disease were Akt1, Bcl-2, and mTOR. GO enrichment analysis indicated an association with neuronal apoptosis. KEGG pathway enrichment analysis identified the key pathway as the PI3K/Akt signaling pathway. Molecular docking results showed that erianin had good binding ability to the three core targets. Cell experiment results demonstrated that compared with the model group, the viability of SH-SY5Y cells in the erianin group was significantly increased, and the degree of cell apoptosis decreased (P < 0.01), and the cell viability was highest when the concentration of erianin was 50 nmol/L. After erianin intervention, the protein expressions of mTOR and Bax in SH-SY5Y cells were significantly decreased, while the protein expressions of Bcl-2, p-Akt, Akt, and PI3K were significantly increased (P < 0.001). Conclusion Erianin may inhibit cell apoptosis by regulating the PI3K/Akt signaling pathway, showing potential therapeutic effects on Alzheimer’s disease.

R285;R286.1

大学生创新创业训练计划项目（国家重点支持领域项目）（202310228063）；大学生创新创业训练项目（国家级一般项目）（202410228053，202410228015，202410228010）；黑龙江省省属本科高校“优秀青年教师基础研究支持计划”（YQJH2024224）；黑龙江中医药大学科研基金项目（博士创新基金）（2019BS05）