【目的】探讨临床中药复方治疗抑郁症的核心药物及其抗抑郁分子机制。【方法】通过中国知网、万方数据和维普网检索相关文献，筛选并整理临床使用的中药复方。通过分析用药频率和中药关联规则，确定柴胡、白芍和郁金为治疗抑郁症的核心中药。利用TCMSP数据库筛选核心药物的活性成分及靶蛋白，并从TTD、OMIM、DrugBank和GeneCards中获取抑郁症相关靶点。通过STRING和Cytoscape数据库构建蛋白质-蛋白质互作（PPI）网络和“核心药物-活性成分-交集靶点”网络，利用Metascape进行基因本体论（GO）富集和京都基因与基因组百科全书（KEGG）通路富集分析。分子对接分析使用RCSB数据库、AutoDockTools和PyMOL，验证关键活性成分与核心靶标的结合活性。【结果】临床中药复方治疗抑郁症的药物以寒性、甘味、苦味和辛味为主，归经以肝经为首。柴胡、白芍和郁金用药频次最高，且“白芍-柴胡”和“郁金-白芍-柴胡”组合支持度最高。PPI网络中，SLC6A4、AKT1和CHRNA4为关键靶点。GO富集分析表明，核心药物通过化学突触传递等生物过程以及G蛋白偶联受体活性等分子功能，在突触膜等部位发挥作用。KEGG通路富集分析结果显示，核心药物可能通过神经活性配体-受体相互作用、钙信号通路等治疗抑郁症。分子对接证实关键活性成分与核心靶标间有强结合活性。【结论】柴胡、白芍和郁金是临床治疗抑郁症的核心中药，其可通过多成分、多靶点、多通路治疗抑郁症。

Objective To explore the core drugs and antidepressant molecular mechanisms of Chinese herbal compound in the clinical treatment of depression. Methods Relevant literature was searched through CNKI，Wanfang and VIP to screen and sort out the Chinese Herbal compounds used in clinical practice. By analyzing the frequency of medication and the association rules of Chinese medicines，Bupleuri Radix，Paeoniae Radix Alba，Curcumae Radix were determined as the core Chinese medicinals for the treatment of depression. The active components and target proteins of these drugs were screened by TCMSP database，and depression-related targets were obtained from TTD，OMIM，DrugBank and GeneCards. Protein-protein interaction（PPI）network and‘core drug-active ingredient-intersection target’network were constructed by STRING and Cytoscape. Gene Ontology（GO）enrichment and Kyoto Encyclopedia of Genes and Genomes（KEGG）pathway enrichment analysis were performed by Metascape. Molecular docking analysis used RCSB database，AutoDockTools and PyMOL to verify the binding activity of key active components with core targets. Results The drugs for the treatment of depression in clinical Chinese herbal compound prescriptions were mainly cold，sweet，bitter and pungent，and the liver meridian was the first. Bupleuri Radix，Paeoniae Radix Alba，Curcumae Radix had the highest frequency of medication，and the combination of“Paeoniae Radix Alba-Bupleuri Radix”and“Curcumae Radix-Paeoniae Radix Alba-Bupleuri Radix”had the highest support. In the PPI network，SLC6A4，AKT1 and CHRNA4 were the key targets. GO enrichment analysis results showed that core drugs play a role in synaptic membranes and other parts through biological processes such as chemical synaptic transmission，as well as molecular functions such as G protein-coupled receptor activity. KEGG pathway enrichment analysis results showed that core drugs may treat depression through neuroactive ligand-receptor interaction，calcium signaling pathway and other pathways. Molecular docking confirmed that there was a strong binding activity between the key active ingredients and the core target. Conclusion Bupleuri Radix，Paeoniae Radix Alba，Curcumae Radix are the core drugs for clinical treatment of depression，which can treat depression through multi-component，multi-target and multi-pathway.

R749.4

国家自然基金青年项目 （编号：82205229）