Study On The Mechanism Of Huayu Qushi Decotion In The Treatment Of Osteoarthritis Based On Bioinformatics

Objective: This study uses bioinformatics research methods to explore the targets and signaling pathways of the active ingredients in Huayu Qushi Decotion to treat osteoarthritis,so as to explore its potential mechanism of action.It provides new clues for future experimental research and clinical application,and enriches the theoretical basis for the treatment of OA with Huayu Qushi Decotion.Methods: The TCMSP database is used to retrieve the active ingredients and targets of traditional Chinese medicine contained in Huayu Qushi Decotion,and the gene names of the targets are queried in the Uniprot database.Use Cytoscape3.8.2 software to construct active ingredients-gene network,and obtain more important effective chemical components through network topology analysis.The OA-related chip datasets GSE12021,GSE55457 and GSE82107 are obtained from the GEO database,and DEGs are screened out after analysis and processing using R software.The target genes of the active ingredients of Huayu Qushi Decotion are intersected with the DEGs to obtain the target genes,and Cytoscape3.8.2 The software draws the active ingredient-target gene network diagram.The PPI network of the target gene is constructed using the "biso Genet" plug-in in Cytoscape 3.8.2software,the core network is obtained by the DC and BC scores,and the key genes and key active ingredients are screened out.GO and KEGG enrichment analysis is performed on the selected target genes using the Bioconductor database,and R software is used to visualize the results.Find key active ingredients in the Pub Chem database and optimize them using Chem3 D.3D structures of the expressed protein of key genes are obtained from the PDB database,and then processed with Py MOL software to obtain their crystal structures.Finally,the software Vina is used for ligand-receptor molecular docking and the free energy of binding is calculated,and the images of ligand-receptor molecular docking are sequentially constructed by Py MOL software for visualization.Results: A total of 90 active ingredients in Huayu Qushi Decotion can act on 235 target genes,among which the active ingredients such as quercetin,luteolin,and wogonin are more important.There are 1978 OA-related DEGs obtained by the gene chip analysis of GEO database,and 42 target genes are obtained after intersection.The key genes are obtained by PPI network analysis: MAPK3,CDKN1 A,JUN,MYC,NFKBIA,FN1.The key active ingredients include naringenin,wogonin,luteolin,tanshinone iia,quercetin,beta-sitosterol and nobiletin.The biological processes involve in target genes mainly include: response to lipopolysaccharide,cytokine activity,caveola,etc.KEGG signaling pathways related to OA mainly include: IL-17 signaling pathway,TNF signaling pathway,Toll-like receptor signaling pathway,HIF-1signaling pathway,PI3K-Akt signaling pathway,etc.Molecular docking technology shows that the binding activity of key active ingredients to key target genes is good.Conclusions:(1)This study preliminarily reveale the mechanism of the multi-component,multi-target and multi-path treatment of osteoarthritis of Huayu Qushi Decotion.(2)The mechanism of action of Huayu Qushi Decotion in the treatment of osteoarthritis is inseparable from the antioxidant,anti-apoptotic and anti-inflammatory effects of key active ingredients such as naringenin,wogonin,luteolin,tanshinone iia,quercetin,beta-sitosterol,nobiletin.(3)Huayu Qushi Decotion can inhibit inflammation and protect cartilage,mainly through key target genes such as MAPK3,CDKN1 A,JUN,MYC,NFKBIA,and FN1,thereby preventing and treating OA cartilage degeneration.(4)Huayu Qushi Decotion mainly through biological processes such as the response to lipopolysaccharide,cytokine activity,pits,and related signaling pathways such as IL-17 signaling pathway,TNF signaling pathway,Toll-like receptor signaling pathway,HIF-1 signaling pathway,and PI3K-Akt signaling pathway,from the inflammatory response,oxidative stress response,apoptosis,autophagy to play a role in the treatment of OA.(5)Through molecular docking technology,it is preliminarily verified that the binding activity of key effective compounds and key target genes is good,and the docking complex is relatively stable.