Study on the Mechanism of Sasanquasaponin in Inhibiting the Progression of Osteoarthritis via the MAPK and PI3K/AKT Pathways.

Sasanquasaponin (SQS) exhibits anti-inflammatory and antioxidant effects, with unknown therapeutic effects in osteoarthritis (OA).This study was conducted to verify the effects of SQS and its molecular mechanism in OA.Specifically, flow cytometry was utilized to assess cell apoptosis, and ELISA was used for evaluating the levels of pro-inflammatory cytokines (IL-6, IL-8, TNF-α) and matrix-degrading enzymes (MMP-3, MMP-13, ADAMTS-4, ADAMTS-5). The targeting effects of SQS on the MAPK and PI3K/AKT pathways were predicted using the molecular docking method.SQS rescued IL-1β-induced apoptosis in human chondrocytes (C-28/I2) in a concentration-dependent manner while suppressing the production of pro-inflammatory cytokines and matrix-degrading enzymes. Bioinformatics prediction identified reliable binding sites for SQS in key proteins of both the MAPK (p38, JNK) and PI3K/AKT (PI3K, AKT) signaling pathways. In IL 1β stimulated C 28/I2 cells, SQS suppressed the excessive activation of p38, JNK, PI3K, and AKT. Moreover, overexpression of these proteins reversed the protective effect of SQS against C-28/I2 apoptosis, as well as its inhibitory effect on the production of pro-inflammatory cytokines and matrix-degrading enzymes.Collectively, SQS alleviates OA inflammation and matrix degradation via inactivation of the MAPK and PI3K/AKT pathways.