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