基于网络药理学和分子对接技术探讨甘草附子汤治疗膝骨关节炎作用机制OA

Objective Evidence suggests that Gancao Fuzi Decoction(GCFZD)demonstrates good clinical efficacy in treating knee osteoarthritis(KOA).To further explore its underlying mechanisms and signaling pathways,this study employed network pharmacology and molecular docking technology for investigation.Methods Active components of GCFZD and their corresponding target proteins were retrieved from the TCMSP database.KOA-related genes were collected from the GeneCards and OMIM databases.The STRING database and Cytoscape software were used to construct a protein-protein interaction(PPI)network,identify core targets,and build a"Herb-Component-Target-Disease"network diagram.Functional enrichment analysis,including gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)pathway analyses,were carried out via relevant software packages based on the Bioconductor platform of R language.Finally,molecular docking was utilized to evaluate the binding affinity between the main active components and the core targets interleukin-6(IL-6),RAC-alpha serine/threonine-protein kinase(Akt1),and tumor necrosis factor(TNF).Results A total of 1028 compounds were screened from the TCMSP database,corresponding to 191 unique potential targets of GCFZD.Cross-analysis identified potential overlapping targets for GCFZD against KOA.PPI network analysis revealed that the core targets associated with KOA treatment included IL-6,TNF,Akt1,interleukin-1 beta(IL-1β),matrix metalloproteinase-9(MMP-9),prostaglandin-endoperoxide synthase 2(PTGS2),caspase-3(CASP3),transcription factor AP-1(JUN),hypoxia-inducible factor 1-alpha(HIF-1A),and epidermal growth factor receptor(EGFR).GO and KEGG enrichment analyses indicated that the primary biological processes involved were the response to lipopolysaccharide,response to molecule of bacterial origin,and the reactive oxygen species metabolic process.The most significantly enriched signaling pathways were the IL-17 signaling pathway,TNF signaling pathway,and HIF-1 signaling pathway.Molecular docking results showed that the main active components had good binding affinity to IL-6,TNF,and Akt1,with the binding to TNF being particularly strong,suggesting that TNF might be the most crucial target for GCFZD's anti-KOA effects.Conclusion GCFZD may alleviate KOA by modulating the response to lipopolysaccharide,the response to molecules of bacterial origin,and the reactive oxygen species metabolic process.Our study reveals the potential molecular mechanism of GCFZD in treating KOA,demonstrating its value for further research and its potential as a new drug candidate.