目的 通过网络药理学探讨柴胡皂苷a在抑郁症治疗中的作用机制。方法 从PubChem、PharmMapper和SwissTarget Prediction数据库中获取柴胡皂苷a的分子结构和潜在靶点。将柴胡皂苷a和抑郁症的共同靶点导入STRING 11.0数据库，构建蛋白相互作用（PPI）网络。利用DAVID 6.8数据库进行基因本体论（GO）和京都基因与基因组百科全书（KEGG）富集分析。结果 本研究共获得柴胡皂苷a靶点408个，抑郁相关靶点3 799个，最终得到200个共同靶点，包括白蛋白（ALB）、丝氨酸/苏氨酸蛋白激酶B（Akt1）、热休克蛋白90 α家族A类成员1（HSP90AA1）、转录信号转导和激活因子3（STAT3）和表皮生长因子受体（EGFR）等。GO和KEGG富集分析表明，癌症、脂质和动脉粥样硬化、前列腺癌、癌症蛋白多糖、内分泌耐药、叉头框-O（FoxO）信号通路、磷酸肌醇-3激酶（PI3K）/Akt信号通路、EGFR酪氨酸激酶抑制剂耐药、Th17细胞分化、催乳素信号通路等通路在柴胡皂苷a抗抑郁中发挥了重要作用。结论 柴胡皂苷a可能通过作用于FoxO、催乳素、PI3K/Akt信号通路及ALB、Akt1、HSP90AA1、STAT3等靶点发挥抗抑郁作用。

Objective To elucidate the mechanism of saikosaponin a in treating depression with network pharmacology. Methods Molecular structure and potential targets of saikosaponin a was obtained from PubChem, PharmMapper and SwissTarget Prediction databases. The common targets of saikosaponin a and depression were imported to the STRING 11.0 database, and then a protein interaction network was constructed. GO and KEGG enrichment were analyzed with DAVID 6.8 database.Results A total of 408 targets of saikosaponin a were obtained and there were 3 799 depression-related targets. A total of 200 common genes were selected as targets of depression including ALB, Akt1, HSP90AA1, STAT3, and EGFR. GO and KEGG analysis suggested that pathways in cancer, lipid and atherosclerosis, prostate cancer, proteoglycans in cancer, endocrine resistance, FoxO signaling pathway, PI3K/Akt signaling pathway, EGFR tyrosine kinase inhibitor resistance, Th17 cell differentiation, and prolactin signaling pathway played an imported role. Conclusion Our results suggested that saikosaponin a may exert its antidepressant effect by acting on FoxO, prolactin, and PI3K/Akt signaling pathways and ALB, Akt1, HSP90AA1, and STAT3 targets.

R285;R286.1

陕西省自然科学基础研究计划（2024JC-YBMS-119，2021JQ-816）；陕西省教育厅重点科学研究计划项目（高校工程研究中心项目）（24JR162）；陕西基础科学（化学、生物学）研究院基础科学研究计划（22JHQ050）