Schisandrin A alleviates chondrocyte senescence and extracellular matrix degeneration by suppressing PI3K/Akt signaling pathway

Osteoarthritis (OA) is a progressive joint disorder characterized by inflammation and metabolic imbalance. Schisandrin A (Sch-A), a bioactive compound from Schisandra sphenanthera, is known for its anti-inflammatory and protective properties. This study investigated the effects of Sch-A on chondrocyte senescence and metabolism using IL-1β-stimulated CHON-001 cells as an in vitro OA model. Sch-A showed no cytotoxicity up to 100 μM and alleviated IL-1β-induced chondrocyte injury. It restored anabolic metabolism, suppressed catabolic activity, and reduced inflammatory and fibrotic responses. Bioinformatics indicated links between Sch-A, cellular senescence, and the PI3K/Akt pathway. Functional assays confirmed that Sch-A suppressed senescence-associated secretory phenotype (SASP) factors, senescence markers, SA-β-galactosidase activity, and PI3K/Akt activation, while PI3K inhibition enhanced its anti-senescent effects. These findings suggest that Sch-A mitigates chondrocyte senescence and metabolic dysregulation by modulating PI3K/Akt signaling, supporting its therapeutic potential for OA.

Osteoarthritis; PI3K/Akt; Schisandrin A; cellular senescence; metabolism.