Corilagin attenuates osteoarthritis progression by coordinating NF-κB inhibition with PI3K/AKT/mTOR-associated autophagy restoration.

BACKGROUND: Osteoarthritis (OA) is characterized by persistent inflammation, extracellular matrix (ECM) degradation, and impaired autophagy. Corilagin is a natural ellagitannin with anti-inflammatory properties, but its effects on OA remain unclear. METHODS: IL-1β-stimulated primary mouse chondrocytes were used to evaluate the effects of Corilagin on cell viability, ECM metabolism, inflammation, signaling pathways, and autophagic flux. Transcriptomic analysis and the autophagy inhibitor 3-methyladenine (3-MA) were used to investigate the underlying mechanisms. Therapeutic efficacy was further assessed in a destabilization of the medial meniscus-induced mouse OA model. RESULTS: Corilagin restored chondrocyte proliferation and increased Aggrecan, collagen II, and SOX9 expression while reducing MMP3, MMP13, iNOS, and COX2 levels. Mechanistically, Corilagin inhibited PI3K/AKT/mTOR and NF-κB signaling, reduced p65 nuclear translocation, and restored autophagic flux, as evidenced by increased Beclin-1 and LC3 II/I levels and decreased p62 accumulation. 3-MA partially abolished these protective effects. In vivo, intra-articular Corilagin administration reduced osteophyte formation, cartilage erosion, proteoglycan loss, OARSI scores, and MMP13 and p62 expression, while restoring Aggrecan expression. CONCLUSION: Corilagin alleviates experimental OA by suppressing inflammatory and catabolic responses and restoring autophagy through inhibition of the NF-κB and PI3K/AKT/mTOR pathways.