Network pharmacology to investigate the potential mechanism of Qianghuo against osteoarthritis and experimental validation

Notopterygium incisum (Qianghuo, QH) is commonly used for Osteoarthritis (OA), yet its bioactive components and molecular targets remain unclear. This study systematically investigated the pharmacological basis and mechanism of QH against OA. Active compounds and targets were screened using TCMSP and GeneCards databases. Protein-protein interaction (PPI), GO, and KEGG enrichment analyses were performed to predict mechanisms. Molecular docking verified binding affinities. In a papain-induced OA rat model, histopathological changes were evaluated using HE and Safranin O-Fast Green staining, while inflammatory cytokine expression and key protein levels were assessed via qRT-PCR and Western blot. Network analysis identified 15 active compounds and 55 targets, with AKT1, MAPK1, and CASP3 as core hubs. Molecular docking demonstrated strong binding energy (< -7 kcal/mol) between active ingredients and these targets. In vivo experiments showed that QH significantly alleviated cartilage erosion, improved histopathological scores, and downregulated mRNA expression of IL-1β, IL-6, and TNF-α. Furthermore, QH significantly inhibited AKT1 and MAPK1 phosphorylation and reduced Cleaved-Caspase-3 levels. In conclusion, QH exerts anti-OA effects by mitigating cartilage degeneration and suppressing inflammation. The mechanism involves inhibiting excessive AKT1/MAPK1 activation, thereby suppressing downstream Caspase-3 cleavage and blocking chondrocyte apoptosis, providing a scientific basis for QH in OA treatment.