基于网络药理学探讨逍遥散“异病同治”抑郁症和干眼症的作用机制

Exploring the Mechanism of Xiaoyao Powder in “Treating Different Diseases with the Same Method” for Depression and Dry Eye Disease Based on Network Pharmacology

摘要: 目的：基于网络药理学探讨逍遥散抗抑郁症和干眼症的分子机制。方法：从TCMSP和GeneCards数据库中筛选逍遥散、抑郁症和干眼症的靶点，并交互获得逍遥散与抑郁症和干眼症的共同靶点。随后运用Cytoscape软件构建“中药–成分–共同靶点”网络及PPI网络，从中筛选出其关键成分和核心靶点。接着借助DAVID数据库对共同靶点进行GO和KEGG富集分析，最后通过Schrodinger Maestro软件对关键成分与核心靶点进行分子对接验证。结果：筛选得到742个逍遥散的靶点及15,835个抑郁症和5907个干眼症靶点，三者有482个共同靶点。PPI网络分析得出核心靶点为TP53、SRC、PIK3CA、PIK3CD。GO富集分析主要涉及对外源性刺激的反应、蛋白磷酸化等生物过程；KEGG富集分析主要涉及EGFR酪氨酸激酶抑制剂耐药性、癌症中的中心碳代谢等。分子对接结果表明，关键成分和核心靶蛋白之间具有良好的结合能力。结论：逍遥散可能通过作用于TP53、SRC、PIK3CA等靶点来共同干预抑郁症和干眼症。

Abstract: Objective: To investigate the molecular mechanism of Xiaoyao Powder in the treatment of depression and dry eye based on network pharmacology. Methods: The targets of Xiaoyao Powder, depression, and dry eye were screened from the TCMSP and GeneCards databases. The common targets of Xiaoyao Powder against both depression and dry eye were obtained through intersection analysis. The “Chinese medicine-component-common target” network and the PPI network were constructed using Cytoscape software to screen the key components and core targets. GO and KEGG enrichment analyses of the common targets were performed using the DAVID database. Molecular docking validation of the key components with the core targets was conducted using Schrodinger Maestro software. Results: A total of 742 targets for Xiaoyao Powder, 15,835 targets for depression, and 5,907 targets for dry eye were screened, yielding 482 common targets among the three. PPI network analysis identified TP53, SRC, PIK3CA, and PIK3CD as core targets. GO enrichment analysis primarily involved biological processes such as response to exogenous stimuli and protein phosphorylation. KEGG enrichment analysis mainly implicated pathways, including EGFR tyrosine kinase inhibitor resistance and central carbon metabolism in cancer. Molecular docking results indicated good binding affinity between the key components and the core target proteins. Conclusion: Xiaoyao Powder may co-regulate depression and dry eye by acting on targets such as TP53, SRC, and PIK3CA.