• Yougui Pill significantly ameliorates cartilage degeneration and reduces serum inflammatory cytokines (TNF-α, IL-18, IL-1β) in a rat model of knee osteoarthritis.
• The therapeutic effect of Yougui Pill is superior to celecoxib in restoring cartilage structure and suppressing pyroptosis-related protein expression.
• Yougui Pill inhibits the PI3K/AKT/NF-κB signaling pathway, leading to downregulation of NLRP3/Caspase1/GSDMD-mediated pyroptosis in chondrocytes.
• This study provides a molecular basis for Yougui Pill as a potential disease-modifying treatment for knee osteoarthritis.