Mechanism of action of New Zhigu Zengsheng Pill in the treatment of osteoarthritis of the knee by using network pharmacology
Objective To explore the potential mechanism of action of New Zhigu Zengsheng Pill in the treatment of osteoarthritis of the knee(KOA)by using network pharmacology.Methods The active constituents and their targets of New Zhigu Zengsheng Pill were screened by traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP)database.GeneCards,OMIM and DisGeNet databases were used to search KOA disease-related targets.Through Venny 2.1.0 online platform,the intersection mapping between the active ingredient target of New Zhigu Zengsheng Pill and the disease-related target of KOA was obtained to obtain the key target(common target)of New Zhigu Zengsheng Pill for treating KOA.The common targets were imported into the String platform construction protein-protein interaction(PPI)network,and the results were imported into Cytoscape 3.7.1 software for topological analysis to extract the core targets.Gene ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Gnomes(KEGG)pathway enrichment analysis were performed on the core targets by using Database for Annotation,Visualization and Integrated Discovery(DAVID)database.The"Active ingredient-key target-pathway"network was constructed by using Cytoscape 3.7.1 software.Results A total of 54 active ingredients were obtained,corresponding to 262 targets,2459 disease targets and a total of 142 targets.Through protein interaction and topological analysis,13 core targets were obtained,and 821 biological processes(BP),94 cell components(CC),139 molecular functions(MF)and 167 pathways were obtained by GO functional enrichment analysis(P<0.05).Topological analysis of the network diagram of"active ingredient-core target-pathway"was performed,and 12 core components such as quercetin,β-sitosterol,luteolin,kaempferol,and 16 key targets such as tumor necrosis factor(TNF),AKT serine/threonine kinase 1(AKT1),interleukin-6(IL-6),vascular endothelial growth factor A(VEGFA),interleukin-1β(IL-1β),and so on were selected.Conclusion New Zhigu Zengsheng Pill may act on AKT1,TNF,VEGFA and other core targets through quercetin,β-sitosterol,kaempferol and other active components,and play a synergistic role in the treatment of KOA through advanced glycation end products-receptor for advanced glycation end products(AGE-RAGE),TNF and other signaling pathways.
New Zhigu Zengsheng PillOsteoarthritis of the kneeNetwork pharmacologyMechanism of actionQuercetinβ-sitosterolKaempferol