The Study Of Molecular Mechanism Of Shexiang Wulong Pill On The Treatment Of Rheumatoid Arthritis Based On Network Pharmacology

Objectives Using network pharmacology technology and Cytoscape visualization software,the aim of this study is to investigate the mechanism of Shexiang Wulong pills in treating rheumatoid arthritis(RA).Methods The compound library of musk,monkshood,black bean,scorpion and earthworm was established using the tools and strategies of the Traditional Chinese Medicine System Pharmacology(TCMSP)and Traditional Chinese Medicine Integrated Database(TCMID);the compound targets were predicted by the Swiss Target Prediction database;AR targets were predicted by Gene Card,OMIM and Dis Genet databases;The compound targets-AR targets interaction network was constructed,and the network was performed GO analysis and KEGG enrichment analysis.Finally,cytoscape software is used to make a visual network diagram of the analysis results.Results A total of 59 compounds and 231 targets were obtained from Shexiang Wulong pills.Protein interaction network analysis showed that ENLP1,akt serine/threonine kinase1(AKT1),ras homolog family member A(RHOA),nuclear factor-kappa B(NF-?B)were the core proteins.The results of the target protein-functional network of Shexiang Wulong pills showed that the target protein of Shexiang Wulong pills was mainly involved in the oxidative stress response,cytochrome-C release,the function of mitochondria and endoplasmic reticulum,and the function regulation of ATP and GTP-related protein kinases.The results of the target protein-pathway network showed that the target protein of Shexiang Wulong pills was mainly involved in amino acid metabolism and nervous system function.1119 RA-related targets were screened,among which,9 targets were intersection targets of three websites.That includes solute carrier family 22 member 4(SLC22A4),protein tyrosine phosphatase non-receptor type 22(PTPN22),peptidyl arginine deiminase4(PADI4),Nuclear factor kappa b inhibitor like 1(NFKBIL1),macrophage migration inhibitory factor(MIF),interleukin 6(IL6),interleukin 10(IL-10),class II major histocompatibility complex transactivator(CIITA)and CD244.There are 40 targets mapping Shexiang Wulong compounds to AR disease,these molecules are mainly involved in regulating process of the immune reaction,infection,NTF alpha signal pathway,T cells activity,MAPK signal pathways and PI3 K signaling pathways,c AMP signal and so on.Targets were analyzed by biological processes analysis,results shows that the top 10 targets mainly involved in transcription start,toxicity response,cell apoptosis,the adjustment of the second messenger;molecular function analysis shows that targets mainly involved in regulating metabolism of sterols,polymerization,enzyme binding activity,DNA binding protein 2 activity,the combination of RNA polymerase activity,as well as the activity of transcription factors;cell components analysis shows that the target proteins are mainly distributed in the mitochondrial membrane,cytoplasm,cell membrane and nucleus pulposus.KEGG analysis showed that the targets were mainly involved in the regulation of immune response,infectious diseases,NTF-signaling pathway,T cell pathway,MAPK signaling pathway,c AMP signal,apoptosis,gene expression regulation,adipocyte adipocyte decomposition regulation and other related pathways.Conclusions 1.Twelve key genes involved in the occurrence and development of RA were analyzed,including NFKB1,MAPK3,BCL2,BAX,CASP8,CASP3,NR3C1,ESR1,ESR2,PGR,PRKCD,IL6,and NOS2.2.The active components of Shexiang Wulong pills,Musk,Black bean,Earthworm and scorpion,obtained 231 targets in total.Through regulating amino acid metabolism,sugar metabolism and related pathways of the nervous system,Shexiang Wulong pills is mainly involved in the regulation of cytochrome C oxidative stress reaction,mitochondrial and endoplasmic reticulum functions,ATP and GTP-related protein kinases and other functions.3.The network pharmacology analysis was carried out on the disease targets of musk,Radix Aconite,Black bean,Earthworm and scorpion and RA of 5 active components of Shexiang Wulong pills.It was found that Shexiang Wulong pills may inhibit RA by regulating immune response,inflammatory response,TNF-signaling pathway,T cell pathway,MAPK signaling pathway,c AMP signaling,and apoptosis pathways.Figure10;Table5;Reference 270...