基于网络药理学探讨四神煎治疗类风湿关节炎的作用机制

目的:基于网络药理学探讨四神煎治疗类风湿关节炎(rheumatoid arthritis,RA)的作用机制.方法:通过中药系统药理数据库和分析平台(traditional chinese medicine systems pharmacology database and analysis platform,TCMSP...

Study on the Mechanism of Sishen Decoction in the Treatment of Rheumatoid Arthritis Based on Network Pharmacology

Objective: To explore the mechanism of Sishen Decoction in the treatment of rheumatoid arthritis(RA) based on network pharmacology.Methods: Through the traditional chinese medicine systems pharmacology database and analysis platform(TCMSP) and encyclopedia of traditional chinese medicine(ETCM),the main chemical components of Sishen Decoction were searched, screened and supplemented in combination with the literature.The smiles structural formula and 2 D structure of chemical components were retrieved through Pubchem organic small molecule bioactivity database.After screening by Swiss ADME database, the chemical components meeting the standard were uploaded toSwiss Target Prediction database to predict drug active targets.The targets related to RA diseases were obtained through human gene database(Gencards),online mendelian inheritance in man(OMIM),therapeutic target database(TTD) and DrugBank database.Wayne diagram was drawn and the common targets of active components of Sishen Decoction and RA were obtained.The protein-protein interaction network of drug and disease common targets was constructed based on String platform.Based on Metascape platform, gene ontology(go) biological function analysis and kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment analysis were carried out.Cytoscape 3.7 1 software was used to construct the "component-target-pathway" network, the network topology parameters of each component and target were obtained by using the function of network analyzer, and the important active components and core targets of Sishen Decoction in the treatment of RA were screened.Results: 60 active components and 353 related targets of Sishen Decoction were obtained by ETCM,TCMSP database and literature search;1 277 potential RA targets were obtained through GeneCards, OMIM,TTD and DrugBank;after mapping the action targets of drug components with RA related targets, 151 targets of Sishen Decoction for RA were obtained;2 322 items were obtained by GO biological function enrichment analysis, including 2089 biological processes, 79 cell components and 154 molecular functions;the enrichment analysis of KEGG pathway obtained 174 signal pathways, mainly involving interleukin-17(IL-17) signal pathway, tumor necrosis factor(TNF) signal pathway, Th17 cell differentiation, osteoclast differentiation and nuclear factor-kappa B(NF-κB) Signal path, etc;network topology analysis shows that the important active components of Sishen Decoction in the treatment of RA are quercetin, luteolin, kaempferol, wogonin and other compounds, and the important target genes are PTGS2,PTGS1,RELA,TNF,NFKB1,IL-6 and so on.Conclusion: Sishen Decoction may regulate the expression of target genes such as PTGS2,PTGS1,RELA,TNF,NFKB1 and IL-6 through active components such as quercetin, luteolin, kaempferol and wogonin, and then regulate biological pathways such as IL-17 signal pathway, TNF signal pathway, Th17 cell differentiation and osteoclast differentiation.