Elucidating the therapeutic mechanisms of Angelica dahurica in knee osteoarthritis: An integrative network pharmacology and molecular docking approach

• Multi-target mechanism : Angelica dahurica interacts with multiple targets (e.g., AR, BCL2, ESR1, PLAU, PRKCA, PTGS1, PTGS2) involved in critical pathways such as NF-kappa B signaling and VEGF signaling. • Functional enrichment : The identified targets are involved in biological processes related to inflammation, apoptosis, and angiogenesis, suggesting a comprehensive therapeutic effect. • Molecular docking validation : The strong binding affinities of key compounds to their targets validate the network pharmacology predictions and support the potential therapeutic efficacy of Angelica dahurica in KOA. This study aims to elucidate the molecular mechanisms underlying the therapeutic effects of Angelica dahurica in knee osteoarthritis (KOA) using an integrated network pharmacology and molecular docking approach. Active compounds of Angelica dahurica were identified using the TCMSP database, and their potential targets were retrieved from Traditional Chinese Medicine Systems Pharmacology (TCMSP) and UniProt databases. KOA-related targets were obtained from GeneCards. Shared targets were identified using Jvenn, and a "compound-target" interaction network was constructed using Cytoscape. Protein-protein interactions (PPIs) were analyzed via Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), and functional enrichment analysis was performed using (RoSS Ihaka and Robert Gentleman) R software. Molecular docking studies were performed for key compounds (β-sitosterol and prangenidin) with their respective targets. Twenty active compounds targeting 62 distinct proteins were identified, with key compounds including β-sitosterol and prangenidin. Thirteen shared targets were identified between Angelica dahurica and KOA, including AR, BCL2, ESR1, PLAU, PRKCA, PTGS1, PTGS2, and VEGFA. Angelica dahurica significantly modulates pathways such as the NF-κB signaling pathway and the VEGF signaling pathway. Key compounds exhibited strong binding affinities to their targets, with docking scores below -6 kcal/mol, indicating strong and favorable binding affinities. Angelica dahurica demonstrates potential in managing KOA through a multi-component, multi-target, and multi-pathway approach. This study provides a solid foundation for further experimental validation and mechanistic investigations into the therapeutic effects of Angelica dahurica against KOA.