半夏白术天麻汤、柴胡疏肝散和逍遥散“同病异治”抑郁症的作用机制分析

Mechanism Analysis of Banxiabaizhutianma Decoction, Chaihushugan Powder and Xiaoyao Powder in Treating Depression by “The Same Disease with Different Treatments”

摘要: 目的：本文采用网络药理学的方法，探讨半夏白术天麻汤、柴胡疏肝散和逍遥散三种中药复方“同病异治”抑郁症的有效成分、作用靶点和作用机制。方法：利用TCMSP和BATMAN-TCM获取三个中药复方的活性成分和药物靶点信息。从NCBI-GEO数据库中筛选抑郁症芯片并结合GeneCards、OMIM、TTD、DrugBank和PharmGKB五个疾病数据库挖掘疾病靶点，比较得到药物–疾病共有靶点。通过DAVID在线数据库和RStudio软件对药物和疾病的共有靶点进行GO富集和KEGG分析，分析三个中药复方“同病异治”抑郁症的信号通路。利用String构建蛋白质互作网络(PPI)并通过Cytoscape3.8.0对PPI进行修饰，运用插件进行拓扑分析和模块分析，筛选三种中药复方“同病异治”抑郁症的潜在靶点。结果：半夏白术天麻汤化学成分为232个、对应的药物靶点有1628个，柴胡疏肝散的化学成分有276个、对应的药物靶点有1353个，逍遥散的化学成分有163个、对应的药物靶点有1413个，其中三个中药复方和抑郁症共有靶点为342个。通过GO富集分析和KEGG通路分析、互作网络分析、拓扑分析和模块分析，发现半夏白术天麻汤、柴胡疏肝散和逍遥散主要通过癌症相关通路、神经活性配体–受体相互作用通路、cAMP信号通路、钙信号通路、MAPK信号通路、PI3K-Akt信号通路等通路干预治疗抑郁症。同时得到PGR、AR、PTGS2、PPARG、ESR1、NR3C2、PPARD、GABRA1、NR3C1和OPRK1这10个基因靶点为三个中药复方共同抗抑郁的潜在靶点；三种中药复方的特有抗抑郁关键靶点是PGR、AR、PTGS2、SCN5A。结论：半夏白术天麻汤、柴胡疏肝散和逍遥散之间存在相同和不同的可作用于抑郁症的化学成分和药物靶点，通过构建“共有和特有化学成分–靶点–疾病”互作网络来阐明三者“同病异治”抑郁症的科学内涵。

Abstract: Objective: To investigate the effective components, action targets and mechanisms of three traditional Chinese medicine compounds of Banxiabaizhutianma Decoction, Chaihushugan Powder and Xiaoyao Powder in treating depression with “the same disease with different treatments” by using the method of network pharmacology. Methods: TCMSP and Batman-TCM were used to obtain the information of active ingredients and drug targets of the three TCM compounds. By screening depression chips from NCBI-GEO database and combining with GeneCards, OMIM, TTD, DrugBank and PharmGKB five disease databases to find disease targets, and then common drug-disease targets were obtained. GO enrichment and KEGG analysis were performed on the common targets of drugs and diseases through DAVID online database and R Studio software, and the signaling pathways of the three TCM compounds in treating depression were analyzed. The protein-protein interaction network (PPI) was constructed with String and modified with Cytoscape3.8.0. The plugin was used for topology analysis and module analysis to screen the potential targets of the three TCM com-pounds for depression by “the same disease with different treatments”. Results: There were 232 chemical components of Banxiabaizhutianma Decoction and 1628 corresponding drug targets; a total of 276 chemical components of Chaihushugan Powder and 1353 corresponding drug targets; in addition, 163 chemical components of and Xiaoyao Powder and 1413 corresponding drug targets; among them, there were 342 targets of the three TCM compounds and depression. Through GO enrichment analysis and KEGG pathway analysis, interaction network analysis, topology analysis and module analysis. It was found that three TCM compounds mainly intervene to treat depression through cancer-related pathways, neural active ligand-receptor interaction pathway, cAMP signaling pathway, calcium signaling pathway, MAPK signaling pathway, PI3K-Akt signaling pathway and other pathways. At the same time, 10 gene targets including PGR, AR, PTGS2, PPARG, ESR1, NR3C2, PPARD, GABRA1, NR3C1 and OPRK1 were identified as potential targets of the three TCM com-pounds. The key antidepressant targets of the three TCM compounds are PGR, AR, PTGS2 and SCN5A. Conclusion: There are the same and different chemical components and drug targets that can act on depression among Banxiabaizhutianma Decoction, Chaihushugan Powder and Xiaoyao Powder. The scientific connotation of “the same disease with different treatments” in treating depression is clarified by constructing the interaction network of “common and unique chemical components-targets-disease”.