Molecular mechanism of the effect of BixiezelanYin on knee osteoarthritis based on network pharmacology and molecular docking.

The BixizelanYin (BXZLY) is a traditional herbal formula for treating damp-heat type knee osteoarthritis (KOA). This study aimed to investigate the potential therapeutic effects of BXZLY on KOA by using network pharmacology and molecular docking. Active ingredients and their corresponding targets of BXZLY were screened through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. The known disease targets of KOA were retrieved from GeneCards and the Online Mendelian Inheritance in Man database. The effective targets of BXZLY for treating KOA were obtained with the Venny platform. A drug-component-target network diagram was constructed using Cytoscape 3.7.2 software, and a protein-protein interaction network was established via the STRING database. The protein-protein interaction network was visualized by Cytoscape 3.7.2 software. The biological functions of the targets wereanalyzed through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis with the DAVID database. The Gene Ontology enrichment and KEGG pathway visualization bubble charts were generated using the OmicShare online platform to explore the biological functions of BXZLY in treating KOA. The main signaling pathways of BXZLY in treating KOA were investigated by KEGG pathway enrichment analysis. Finally, AutoDockTools software was used for molecular docking validation of the key molecules of the drug and the key proteins of the disease. A total of 108 active compounds and 280 target proteins of BXZLY were identified. There were 2816 disease-related targets related to KOA, among which 99 were targeted by BXZLY for KOA treatment. Key compounds included β-sitosterol, stigmasterol, campesterol, quercetin, and dioscin. Core target proteins consisted of STAT3, ESR1, EGFR, JUN, and PTGS2. The pathways mainly involved the advanced glycation end products - receptor for advanced glycation end products, estrogen, HIF-1, and relaxin signal pathways. Molecular docking showed a strong binding affinity between active ingredients and core target proteins. Docking candidates were selected based on oral bioavailability ≥ 30%, drug-likeness ≥ 0.18, and degree values in Cytoscape. This strategy ensured a reliable selection of compounds with high therapeutic relevance. BXZLY provides a comprehensive therapeutic strategy for KOA treatment by regulating cell proliferation and alleviating inflammation through its multi-component, multi-target, and multi-pathway effects.