目的 利用网络药理学和分子对接技术探讨细叶远志皂苷的抗抑郁作用机制。方法 通过Swiss Target Prediction和PharmMapper数据库预测细叶远志皂苷的靶点。在OMIM、GeneCards、TTD和DisGeNET数据库中获得抑郁症靶点。利用Veeny网站得到交集靶点，并在STRING数据库和Cytoscape软件中获得蛋白质–蛋白质相互作用（PPI）网络图；通过DAVID数据库对交集靶点进行基因本体（GO）和京都基因与基因组百科全书（KEGG）富集分析；使用Autodock Vina软件进行分子对接。结果 共获得细叶远志皂苷靶点308个和抑郁症靶点5 962个，取交集后得到217个交集靶点。根据度值、介数中心性和接近中心性筛选出78个核心靶点，其中前5个为丝氨酸/苏氨酸蛋白激酶B（Akt1）、白蛋白（ALB）、热休克蛋白90α家族A类成员1（HSP90AA1）、转录信号转导和激活因子3（STAT3）和原癌基因酪氨酸蛋白激酶（SRC）。GO和KEGG富集分析表明MAPK级联正调控、信号转导、磷脂酰肌醇3-激酶/蛋白激酶B信号转导的正调控、ERK1和ERK2级联的正向调控、腺苷酸环化酶激活肾上腺素能受体信号通路、催乳素信号通路、叉头框O（Fox O）信号通路在细叶远志皂苷的抗抑郁中发挥了关键作用。此外，分子对接结果显示，细叶远志皂苷与Akt1、ALB、HSP90AA1、SRC、STAT3表现出较好的结合活性。结论 Akt1、ALB、HSP90AA1、SRC、STAT3及相关通路可能与细叶远志皂苷改善抑郁行为存在潜在关联，为其后续在抑郁症的机制研究与靶点开发中提供了候选方向。

Objective To explore the antidepressant mechanism of tenuifolin using network pharmacology and molecular docking technology. Methods The targets of tenuifolin were predicted using the Swiss Target Prediction and PharmMapper databases. Depression-related targets were obtained from the OMIM, GeneCards, TTD, and DisGeNET databases. The common targets were identified via the Venny website, and the protein-protein interaction (PPI) network was constructed using the STRING database and Cytoscape software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of the common targets were performed using the DAVID database. Molecular docking was conducted with AutoDock Vina software. Results A total of 308 targets for tenuifolin and 5 962 depression-related targets were obtained, and 217 common targets were identified after taking the intersection. Based on degree, betweenness centrality, and closeness centrality, 78 core targets were screened out, among which the top five were serine/threonine-protein kinase B (Akt1), albumin (ALB), heat shock protein 90α family class A member 1 (HSP90AA1), signal transducer and activator of transcription 3 (STAT3), and proto-oncogene tyrosine-protein kinase (SRC). GO and KEGG enrichment analyses indicated that the positive regulation of MAPK cascade, signal transduction, positive regulation of phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt1) signaling transduction, positive regulation of ERK1 and ERK2 cascade, adenylyl cyclase-activating adrenergic receptor signaling pathway, prolactin signaling pathway, and FoxO signaling pathway play key roles in the antidepressant effect of tenuifolin. In addition, molecular docking results showed that tenuifolin exhibit good binding activity with Akt1, ALB, HSP90AA1, SRC, and STAT3. Conclusion Akt1, ALB, HSP90AA1, SRC, STAT3, and related pathways may be potentially associated with the improvement of depressive behavior by tenuifolin, providing candidate directions for subsequent mechanistic research and target development in depression.

陕西省教育厅重点科学研究计划项目（24JR162）；陕西省大学生创新创业训练计划项目（S202510722099）；咸阳师范学院重点项目（XSYK25019）