目的 通过网络药理学及分子对接探讨灯盏花乙素改善阿尔茨海默病的作用机制。方法 通过TCMSP、HERB 2.0、SwissTargetPrediction、SEA数据库汇总、去重并筛选灯盏花乙素潜在靶点，借助Uniprot数据库对靶点名称进行标准化校正；采用GeneCards、OMIM数据库获取阿尔茨海默病疾病靶点；使用Venny 2.1.0筛选药物-疾病交集靶点，将交集基因导入STRING 12.0平台构建蛋白质相互作用（PPI）网络；利用Cytoscape 3.10.3软件及CytoNCA 2.6.0插件筛选核心靶点；基于Metascape开展基因本体论（GO）、京都基因和基因组百科全书（KEGG）富集分析，并借助微生信平台绘制富集可视化图；采用AutoDock Vina开展灯盏花乙素与核心靶点的分子对接，评价二者结合活性。结果 共筛选获得灯盏花乙素潜在靶点108个、阿尔茨海默病相关靶点2 279个，药物与疾病交集靶点53个。GO富集得到1 044条生物过程、47项细胞组分、64项分子功能条目；KEGG富集得到177条信号通路，包含白细胞介素（IL）-17、肿瘤坏死因子-α（TNF-α）等炎症相关通路。PPI网络拓扑分析筛选得到IL-6、TNF-α、IL-1β、蛋白激酶B1（Akt1）、表皮生长因子受体（EGFR）等23个核心靶点。分子对接结果表明，灯盏花乙素与IL-6、TNF-α、IL-1β、EGFR的结合能均低于-7.0 kcal/mol，其中与EGFR结合能为-8.2 kcal/mol，结合活性强；与Akt1结合能为-6.8 kcal/mol，结合活性较好。结论 灯盏花乙素可通过多靶点、多通路协同调控发挥干预阿尔茨海默病的潜在保护作用。

Objective To explore the mechanism of scutellarin in ameliorating Alzheimer’s disease by network pharmacology and molecular docking. Methods The potential targets of scutellarin were collected, deduplicated and screened from TCMSP, HERB2.0, SwissTargetPrediction, and SEA databases, followed by standardization of target names using the Uniprot database. Alzheimer’s disease-related disease targets were retrieved from GeneCards and OMIM databases. Venny 2.1.0 was used to screen the overlapping targets between drug and disease. The overlapping genes were imported into the STRING 12.0 platform to construct a protein-protein interaction (PPI) network. Cytoscape 3.10.3 software with the CytoNCA 2.6.0 plugin was applied to screen core targets. GO and KEGG enrichment analyses were performed via Metascape, and enrichment visualization diagrams were plotted using the Microbioinfo online platform. AutoDock Vina was adopted to conduct molecular docking between scutellarin and core targets to evaluate their binding affinity. Results A total of 108 potential targets of scutellarin and 2 279 Alzheimer’s disease-related targets were obtained, among which 53 targets were shared. GO enrichment yielded 1 044 biological process terms, 47 cellular component terms and 64 molecular function terms. A total of 177 signaling pathways were identified by KEGG enrichment, including inflammatory pathways such as IL-17 and TNF-α pathways. Twenty-three core targets including IL-6, TNF-α, IL-1β, Akt1, and EGFR were screened by PPI network topological analysis. Molecular docking results showed that the binding energies of scutellarin with IL-6, TNF-α, IL-1β and EGFR were all lower than -7.0 kcal/mol. The binding energy of scutellarin to EGFR was -8.2 kcal/mol, indicating strong binding affinity, while the binding energy to Akt1 was -6.8 kcal/mol with favorable binding affinity. Conclusion Scutellarin may exert potential neuroprotective effects against Alzheimer’s disease through synergistic regulation of multiple targets and pathways.

R285;R286.1

国家自然科学基金资助项目（82360873）；贵州中医药大学研究生教育创新计划项目（YCXKYB2023017）；贵州中医药大学大学生创新创业项目（S202610662028）