基于网络药理学研究黄连-吴茱萸干预抑郁症的作用机制

Mechanism of Coptidis Rhizoma and Euodiae Fructus in the Intervention of Depression Based on Network Pharmacology

目的:明确黄连-吴茱萸干预抑郁症的成分(群)及作用靶点,探讨黄连-吴茱萸治疗抑郁症的作用机制。方法:采用中药系统药理学数据库与分析平台,筛选出黄连-吴茱萸潜在活性成分,并在Swiss Target Prediction数据库中筛选出活性成分作用靶点。借助基因组注释(Gene Card)数据库,预测和筛选抑郁症疾病相关靶点。采用Cytoscape软件,构建"成分-靶点-疾病"网络,同时运用STRING数据库平台构建蛋白质相互作用网络。利用DAVID平台和R语言进行基因本体(gene ontology,GO)功能富集分析和京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)通路富集分析。结果:筛选得到黄连-吴茱萸潜在活性成分共41个,其中黄连11个,吴茱萸27个,黄连-吴茱萸共有成分3个,通过"成分-靶点-疾病"网络节点分析,进一步得到黄连-吴茱萸干预抑郁有效成分10个,主要有小檗碱、β-谷甾醇、吴茱萸次碱和巴马汀等。黄连-吴茱萸能够通过作用于PTGS2、ACHE、MAOA、AR、BCHE及DRD2等靶点,调控血清素能突触通路、神经活性配体-受体互作通路、钙信号通路、cAMP受体通路和c GMP-PKG通路等信号转导干预抑郁症。结论:本研究初步阐明了黄连-吴茱萸干预抑郁症的物质基础和作用机制,在一定程度上揭示了黄连-吴茱萸治疗抑郁症的整体性和系统性。

OBJECTIVE:To identify the components(groups)and targets of coptidis rhizoma and euodiae fructus in the intervention of depression,and explore the mechanism of coptidis rhizoma and euodiae fructus in the treatment of depression.METHODS:The potential active components of coptidis rhizoma and euodiae fructus were screened out from traditional Chinese medicine systems pharmacology database and analysis platform.The target of active components was selected in Swiss Target Prediction database.With the help of the Gene Card database,relevant targets for depression diseases were predicted and extracted.Cytoscape software was used to construct"component-target-disease"network,and STRING database platform was used to construct the protein interaction network.Gene Ontology(GO)function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed by using David platform and R language.RESULTS:A total of 41 potential active components of coptidis rhizoma and euodiae fructus were extrected,including 11 cases of coptidis rhizoma,27 cases ofeuodiae fructus,and3 cases of coptidis rhizoma and euodiae fructus.Through the analysis of"component-target-disease"network node,10 active components of coptidis rhizoma and euodiae fructus were further obtained,which mainly included berberine,β-sitosterol,euodiae fructus rutaecarpine and palmatine.By acting on targets of PTGS2,ACHE,MAOA,AR,BCHE and DRD2,coptidis rhizoma and euodiae fructus could regulate the signal transduction of serotonergic synaptic pathway,neuroactive ligand-receptor interaction pathway,calcium signaling pathway,c AMP receptor pathway and c GMP-PKG pathway in the intervention of depression.CONCLUSIONS:This study preliminarily clarifies the material basis and mechanism of coptidis rhizoma and euodiae fructus in the intervention of depression,and reveals the integrity and systematicness of coptidis rhizoma and euodiae fructus in the treatment of depression to a certain extent.