基于网络药理学探讨二妙散干预特应性皮炎的分子靶点和机制

The molecular targets and therapeutic mechanisms of Er Miao San treating atopic dermatitis based on network pharmacology

目的通过网络药理学方法研究二妙散干预特应性皮炎的药理机制,分析其作用的活性成分、分子靶点和信号通路。方法通过TCMSP和Drugbank数据库获得二妙散活性成分和靶点。通过GEO数据库分析差异表达基因,获得特应性皮炎疾病靶点。通过Cytoscape的Bisogenet和CytoNCA插件获得二妙散治疗特应性皮炎的靶基因。通过DAVID数据库进行GO和KEGG富集分析。结果经筛选获得二妙散12种活性成分和107个靶点;鉴定出274个特应性皮炎差异表达基因(矫正P值<0.005和|log2(差异倍数)|>1.5)。得到187个二妙散治疗特应性皮炎的靶基因。靶基因的功能注释与端粒组织、蛋白异四聚体化、基因表达调控等相关。PI3K-Akt、MAPK、HIF-1信号通路等20条通路显著性富集。MAPK1、AKT、RELA、和TP53等多个基因为二妙散基因通路网络中干预特应性皮炎的关键基因。结论二妙散中槲皮素、四氢小檗碱、豆甾醇等核心成分可能通过参与PI3K-Akt、MAPK、HIF-1等信号通路,调控MAPK1、AKT、RELA和TP53等基因靶点,治疗特应性皮炎。

Objective To explore the molecular targets and therapeutic mechanism of Er Miao San in the treatment of atopic dermatitis(AD),analyzing its active ingredients,moleculartargets and network analysis.Methods The active ingredients and targets of Er Miao San were obtained from Traditional Chinese Medicine Systems Pharmacology Database(TCMSP)and Drugbank databases.The differential expression genes of AD were obtained by Intergovernmental Group on Earth Observations(GEO)database.The target genes of Er Miao San in the treatment of AD were obtained by using Cytoscape plugin Bisogenet and CytoNCA.Enrichment analysis was obtained from the DAVID database.Results In total,12 active ingredients and 107 targets of Er Miao San were screened out by TCMSP and Drugbank databases;274 differential expression genes(with an adjust P value<0.005 and|log2(fold change)|>1.5)were identified between AD patient and control groups using the intergovernmental Group on Earth Observations(GEO)database.187 target genes of Er Miao San against AD were finally identified by using Cytoscape plugin Bisogenet and CytoNCA.The functional annotations of target genes were related to telomere organization,protein heterotetramerization,regulation of gene expression and so on.Twenty pathways including PI3K-Akt,MAPK and HIF-1 signaling pathway were significantly enriched.Several genes including MAPK1,AKT,RELA and TP53 were the key genes in the gene-pathway network of Er Miao San treating AD.Conclusion This study suggested that quercetin,tetrahydroberberine,stigmastol and other core ingredientss in Er Miao San may treat AD by participating in PI3K-Akt,MAPK,HIF-1 and other signaling pathways,and regulating the core gene targets of MAPK1,Akt,Rela and TP53.