Mechanism Research Of Shentong Zhuyu Decoction In The Treatment Of Osteoporosis Based On Network Pharmacology

ObjectiveThe mechanism of Shentong Zhuyu decoction in treating osteoporosis was studied through network pharmacology analysis,and the potential molecular targets and signal pathways of Shentong Zhuyu decoction in the treatment of osteoporosis were identified.Meanwhile,the binding stability between key molecular targets and effective active ingredients was determined by molecular docking technology.MethodsThe active ingredients of Shentong Zhuyu decoction were retrieved by TCMSP and TCMID databases,and the active ingredients were predicted by ADME screening criteria.The molecular targets of the active ingredients were obtained by Pub Chem and Swiss Target Prediction databases.OMIM,Genecards and Dis Ge NET databases were used to obtain the molecular targets of osteoporosis.Taking the intersection of molecular targets of drugs and diseases.The obtained common molecular targets were analyzed by PPI network using STRING database.Then,Metascape database was used to do enrichment analysis of Genetic ontology（GO）and Kyoto Encyclopedia of Genes and Genomes（KEGG）.Cytoscape 3.8.2 software was used to filtrate key molecular targets for common molecular targets,and PDB database was used to download the molecular structure of key molecular targets.Pub Chem database was used to download the 3D structure of active components with better activity.Pymol,ADT and Auto Dock were used to conduct molecular docking operation between molecular targets and active ingredients.Finally,Pymol software was used to perform visual operation on the analysis results.ResultsThere were 363 active components and 1058 molecular targets in Shentong Zhuyu decoction,2812 molecular targets in osteoporosis,and 400 common molecular targets in Shentong Zhuyu decoction and osteoporosis.3901 GO items were obtained by GO enrichment analysis.In terms of molecular function,molecular targets mainly affect nuclear receptor activity,steroid hormone receptor activity and protein tyrosine kinase activity.In terms of cell components,molecular targets form RNA polymerase transcription factor complexes,cytoplasmic cysts,nuclear transcription factor complexes,etc.In terms of biological processes,these targets mainly involve the response of steroid hormone,the metabolic process of steroid hormone,senescence,etc.A total of 178 signaling pathways were obtained by KEGG enrichment analysis,including many classic signaling pathways: PI3k-Akt signaling Pathway,MAPK Signaling Pathway,c AMP signaling Pathway,TGF-Beta signaling Pathway,etc.However,these signaling pathways mainly involve biological processes such as apoptosis,autophagy,inflammatory response,cell senescence and immune regulation.Molecular docking analysis showed that IL-6,TNF,AKT1 and TP53 had stable binding with quercetin、stigmasterol、beta-sitosterol and kaempferol.ConclusionShentong Zhuyu decoction can mediate inflammatory response,hormone receptors,apoptosis and other activity of signaling pathways,and affects the function of AKT1,TP53,IL-6,TNF and other molecular targets,and regulates osteoporosis with multi-target and multi-signal pathways.