Exploring The Mechanism Of Guhuaisikangfu Pill In The Treatment Of Steroid-induced Avascular Necrosis Of Femoral Head Based On Network Pharmacology And Molecular Docking

Objective: 1.The network pharmacology method was used to predict the effective ingredients,targets and action pathways of the Guhuaisikangfu Pill in the treatment of Steroid-induced avascular necrosis of femoral head(SANFH),so as to reveal the systematic and diversified complex mechanism of the Guhuaisikangfu Pill in the treatment of SANFH.2.Molecular docking technology was used to verify the core components and targets of Guhuaisikangfu Pill,in order to provide a theoretical basis for subsequent basic research and clinical research.Methods: 1.The active ingredients and targets of each traditional Chinese medicine(TCM)in the Guhuaisikangfu Pill were collected by means of TCMSP database,ETCM database and literature search.2.The related targets of SANFH were obtained from Gene Cards database and OMIM database.3.The R software script was used to take the intersection of the therapeutic targets of the active ingredients of Guhuaisikangfu Pill and the disease targets of SANFH,and the intersection targets were used as potential targets for the treatment of SANFH by Guhuaisikangfu Pill.4.The protein-protein interaction(PPI)network analysis was carried out on the potential targets through the STRING database,and the R software script was used to extract the top 30 targets with higher degrees and obtain the corresponding active ingredients.Based on this,the action model of Guhuaisikangfu Pill in the treatment of SANFH was constructed.Then,Cytoscape software was used to extract the core target according to the conditions set by the degree value,and the effective ingredients corresponding to the core target was the core ingredients.Finally,PPI network analysis was performed on the core targets using the STRING database again to obtain the interaction relationship between the core targets.5.Gene ontology(GO)enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed on the intersection targets using R software script and Metascape database,respectively.6.Auto Dock Tools software was used to verify the molecular docking of core ingredients and targets,and Py MOL software was used to visualize some of the docking patterns.Results: 1.The active ingredients and action targets of 22 TCM in the Guhuaisikangfu Pill were 229 and 364,respectively.2.Obtained 2042 SANFH disease targets.3.Obtained 217 potential targets of Guhuaisikangfu Pill in the treatment of SANFH.4.The PPI network relationship diagram of the core targets and the action mode diagram of the Guhuaisikangfu Pill in the treatment of SANFH were constructed;9 core targets for the treatment of SANFH by Guhuaisikangfu Pill were confirmed,namely AKT1,ALB,IL6,TP53,MAPK3,TNF,VEGFA,JUN,EGF,corresponding to the active ingredient information,a total of 13 core ingredients were confirmed,respectively,kaempferol,beta-carotene,quercetin,luteolin,Aloe emodin,(-)-Epigallocatechin gallate,diosgenin,wogonin,baicalein,matrine,beta-sitosterol,formononetin,Rhein.5.A total of 187 GO items including biological processes,molecular functions,and cellular components were obtained by applying R software scripts for GO function analysis,including transcription factor binding,phosphatase binding,nuclear receptor activity,steroid hormone receptor activity,cytokine activity,receptor and ligand activity and other biological processes.A total of 200 biological process entries,117 molecular function entries,and 92 cellular component entries were obtained from GO functional analysis using the Metascape database,all of which involved a variety of biological processes.A total of 179 pathway entries were obtained by applying R software script to KEGG pathway enrichment analysis.Among the pathway entries,PI3K-AKT signaling pathway,lipid and atherosclerosis signaling pathway,IL-17 signaling pathway,HIF-1signaling pathway,and TNF signaling pathway were closely related to SANFH and had a high degree of enrichment.6.Molecular docking confirmed that 13 core ingredients could spontaneously bind to 9 core targets,among which AKT1,TP53,TNF and EGF combined well with most of the core ingredients.Conclusions: 1.Through the network pharmacology method,it was revealed to a certain extent that the Guhuaisikangfu Pill play the role of treating SANFH through multi-component,multi-target and multi-way.2.Molecular docking indicated that Guhuaisikangfu Pill may mainly regulate multiple signaling pathways,mainly the PI3K-AKT signaling pathway,through the effects of core components on core targets,especially AKT1,TP53,TNF and EGF,to promote osteoblast differentiation,improving bone metabolism,reducing inflammatory response and promoting angiogenesis to complete the prevention and treatment of SANFH.