Objective:To investigate the therapeutic mechanism of Yishen Qianggu Mixture for kidney-yang deficiency type osteoporosis(OP)based on network pharmacology.Methods:The OP-related targets were retrieved from DrugBank and other databases.The active ingredients and targets of Yishen Qianggu Mixture were excavated through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and other databases.After obtaining the intersection targets between drugs and diseases,the protein-protein interaction(PPI)network was constructed,and Kyoto Encyclopedia of Genes and Genomes(KEGG)and Gene Ontology(GO)enrichment analyses were performed on the intersection targets.The enrichment results were visualized.Based on the Degree value of the PPI network,key ingredients and targets were screened for molecular docking and molecular dynamics simulations.Results:The active compounds of Yishen Qianggu Mixture include quercetin,stigmasterol,lutein,kaempferol,etc.,and there are 149 intersection targets between drugs and OP.Through PPI analysis,the core targets of Yishen Qianggu Mixture for OP treatment were obtained,including threonine kinase 1(AKT1),interleukin-1β(IL-1β),tumor necrosis factor(TNF),tumor protein P53(TP53),glyceraldehyde 3-phosphate dehydrogenase(GAPDH),matrix metalloproteinase 9(MMP9),and estrogen receptor 1(ESR1).The enrichment of KEGG signaling pathways mainly includes hypoxia-inducible factor-1(HIF-1)and mitogen-activated protein kinase(MAPK)signaling pathways.The biological processes in GO enrichment analysis mainly include positive regulation of RNA polymerase Ⅱ and positive regulation of cell proliferation.Through molecular docking and molecular dynamics simulations,the MMP9-quercetin complex is the most stable,followed by ESR1-stigmasterol,AKT1-lutein,and AKTl-kaempferol complexes.Conclusion:The active ingredients of Yishen Qianggu Mixture,such as quercetin,stigmasterol,lutein,and kaempferol,act on key targets such as AKT1,IL-1β,TNF,and TP53 to play a therapeutic role in kidney-yang deficiency type OP.
维普
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