Objective:In this study,we used network pharmacology and molecular docking technology to analyze the mechanism of Bushen Tongluo granule in the treatment of osteoarthritis.Methods:The main active components and corres...Objective:In this study,we used network pharmacology and molecular docking technology to analyze the mechanism of Bushen Tongluo granule in the treatment of osteoarthritis.Methods:The main active components and corresponding targets of Bushen Tongluo granule were screened from thetraditional Chinese medicine systems pharmacology database.The targets related to osteoarthritis were collected from the Online Mendelian Inheritance in Man,Therapeutic Target database,GeneCards,Pharmacogenomics Knowledgebases and Drugbank databases.Cytoscape3.9.0 software was used to construct the action network diagram of“Bushen Tongluo Granule-Active Component-Target”.Builded a protein-protein interaction network from the STRING database.The Bioconductor platform and R language 4.0.3 were used for Gene Ontologyfunction andKyoto Encyclopedia of Genes and Genomespathway enrichment analysis.Then,selected the pathway most associated with osteoarthritis for specific analysis.Finally,the core genes were screened and verified by molecular docking using AutoDockTools software.Results:71 principal components of Bushen Tongluo granule and 183 potential therapeu-tic targets for osteoarthritis were obtained.Twenty-eight key targets of Bushen Tongluo granulein the treatment of osteoarthritis are enriched in 158 pathways.Among them,the tumor necrosis factor signaling pathway,interleukin-17 signaling pathway,Toll-like receptor signaling pathway,T helper cell 17 cell differentiation and hypoxia-inducible factor-1signaling pathway involved in key targets are closely related to osteoarthritis.The relevant vital targets were involved in the regulation of DNA transcription factor activity,the response to chemical stress,the response to reactive oxygen species,the response to oxidative stress,the proliferation of muscle cells,the proliferation of epithelial cells and the biological processes such as responses to lipopolysaccharides,responses to molecules of bacterial origin.Molecular docking showed that protein kinase B 1-β-sitosterol,the tumor necrosis factor-naringenin,interleukin-6-luteolin,mitogen-activated protein kinase-quercetin,vascular endothelial growth factor A-quercetin and prostaglandin-endoperoxide synthase 2-luteolin have strong docking activities.Conclusions:Bushen Tongluo granule can reduce the inflammatory response and inhibit articular cartilage angiogenesis in the treatment of osteoarthritis,which may be achieved by regulating the inflammatory signaling pathway and hypoxia-inducible factor-1 signaling pathway.展开更多
基金supported by G20 Support and Guarantee Project of Beijing Municipal Science and Technology Commission(Z151100003815013).
文摘Objective:In this study,we used network pharmacology and molecular docking technology to analyze the mechanism of Bushen Tongluo granule in the treatment of osteoarthritis.Methods:The main active components and corresponding targets of Bushen Tongluo granule were screened from thetraditional Chinese medicine systems pharmacology database.The targets related to osteoarthritis were collected from the Online Mendelian Inheritance in Man,Therapeutic Target database,GeneCards,Pharmacogenomics Knowledgebases and Drugbank databases.Cytoscape3.9.0 software was used to construct the action network diagram of“Bushen Tongluo Granule-Active Component-Target”.Builded a protein-protein interaction network from the STRING database.The Bioconductor platform and R language 4.0.3 were used for Gene Ontologyfunction andKyoto Encyclopedia of Genes and Genomespathway enrichment analysis.Then,selected the pathway most associated with osteoarthritis for specific analysis.Finally,the core genes were screened and verified by molecular docking using AutoDockTools software.Results:71 principal components of Bushen Tongluo granule and 183 potential therapeu-tic targets for osteoarthritis were obtained.Twenty-eight key targets of Bushen Tongluo granulein the treatment of osteoarthritis are enriched in 158 pathways.Among them,the tumor necrosis factor signaling pathway,interleukin-17 signaling pathway,Toll-like receptor signaling pathway,T helper cell 17 cell differentiation and hypoxia-inducible factor-1signaling pathway involved in key targets are closely related to osteoarthritis.The relevant vital targets were involved in the regulation of DNA transcription factor activity,the response to chemical stress,the response to reactive oxygen species,the response to oxidative stress,the proliferation of muscle cells,the proliferation of epithelial cells and the biological processes such as responses to lipopolysaccharides,responses to molecules of bacterial origin.Molecular docking showed that protein kinase B 1-β-sitosterol,the tumor necrosis factor-naringenin,interleukin-6-luteolin,mitogen-activated protein kinase-quercetin,vascular endothelial growth factor A-quercetin and prostaglandin-endoperoxide synthase 2-luteolin have strong docking activities.Conclusions:Bushen Tongluo granule can reduce the inflammatory response and inhibit articular cartilage angiogenesis in the treatment of osteoarthritis,which may be achieved by regulating the inflammatory signaling pathway and hypoxia-inducible factor-1 signaling pathway.
