基于网络药理学四逆散治疗抑郁症的作用机制探讨

Research on mechanism of Sini Powder in treatment of depression based on network pharmacology

目的探讨四逆散治疗抑郁症的作用机制。方法借助中药系统药理学分析平台(TCMSP)检索四逆散中柴胡、白芍、枳实、甘草的化学成分和作用靶点,通过OMIM、TTD、Drugbank、Digsee等多个数据库查询与抑郁症(depression)相关的基因。通过Uni Prot数据库查询靶点对应的基因,进而运用Cytoscape 3.2.1构建化合物-靶点(基因)网络、蛋白相互作用(PPI)网络筛选出核心靶点,最后通过DAVID进行基因本体(GO)功能富集分析和基于京都基因与基因组百科全书(KEGG)通路富集分析,预测其作用机制。结果化合物-靶点网络包含121个化合物和相应靶点259个,关键靶点涉及PTGS2、CALM1、ESR1、HSP90AA1、AR等。PPI核心网络包含15蛋白,关键蛋白涉及CASP3、CHRM2、CYP3A4等。GO功能富集分析得到GO条目375个(P<0.05),其中生物过程(BP)条目307个,细胞组成(CC)条目37个,分子功能(MF)条目31个。KEGG通路富集筛选得到37条信号通路(P<0.05),涉及神经活性配体-受体相互作用信号通路、多巴胺信号通路、IL-17信号通路等。结论四逆散中的有效活性成分主要通过作用于CASP3、CHRM2、DRD1等15个关键靶点调节多条信号通路从而发挥抗抑郁作用。

Objective To investigate the mechanism of depression by Sini Powder.Methods The chemical composition and targets of Bupleuri Radix,Paeonia Radix Alba,Aurantii Fructus Immaturus,and Glycyrrhizae Radix et Rhizoma were searched by the analysis of traditional Chinese medicine system pharmacology platform(TCMSP).Depression related genes were screened from OMIM,TDD,Drugbank,and Digsee multiple databases.The target corresponding genes were searched through UniProt,GeneCards,and PubMed database query and then Cytoscape 3.2.1 was used to build compound-targets(genes)networks,protein interaction(PPI)filter core targe;At last,the enrichment of gene ontology(GO)function analysis by DAVID based on the Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis was carried out,and the mechanism of its action research was predicted.Results The compound-target network contained 121 compounds and the corresponding 259 targets,and the key targets involved PTGS2,CALM1,ESR1,HSP90 AA1,AR,etc.The PPI core network contained 15 proteins,key proteins involved in CASP3,CHRM2,CYP3 A4,and etc.The function enrichment analysis of GO was 375(P<0.05),of which there were 307 biological processes(BP),and 37 related items of cell composition(CC),and 31 molecular function(MF)items.37 related items of cell composition(CC),and 31 molecular function(MF)items.There were 37 signal pathways(P<0.05)in KEGG pathway enrichment screening,involving neuroactive ligand-receptor interaction,dopaminergic synapse,IL-17 signaling pathway and so on.Conclusion The active components in Sini Powder play an antidepressant role by acting on 15 key targets such as CASP3,CHRM2,DRD1 to regulate multiple signaling pathways.