Diallyl Disulfide Protects Chondrocytes against Lipopolysaccharide-Induced Apoptosis, Extracellular Matrix Degeneration, and Inflammation via Inhibition of the NF-κB/NLRP3 Signaling Pathway

Diallyl disulfide (DADS) holds anti-inflammatory, anti-oxidant, and immunomodulatory properties and represses nuclear factor-κB (NF-κB)-dependent activation of NLRP3 inflammasomes. However, whether DADS alleviates chondrocyte injury by modulating NF-κB-dependent activation of the NLRP3 inflammasome remains unclear. In this study, lipopolysaccharide (LPS)-stimulated chondrocytes were used as an in vitro model of osteoarthritis (OA) to investigate the effects of DADS. Effects of DADS treatment on cell viability, apoptosis, extracellular matrix (ECM) degradation, and inflammation in chondrocytes were determined via several experiments. Western blot analysis was employed to examine the expression levels of NLRP3 inflammasome components and NF-κB signaling molecules. To determine whether DADS could act through the NF-κB pathway, caffeic acid phenethyl ester (CAPE), a specific NF-κB inhibitor, was used as a comparator. DADS treatment impaired LPS-induced chondrocyte apoptosis, ECM degeneration, and inflammation in a concentration-dependent manner. This was accompanied by a marked reduction in phosphorylated p65 level and downregulation of NLRP3, ASC, and Caspase-1 protein expression levels. Notably, CAPE exerted similar protective effects as DADS, reducing LPS-induced apoptosis, ECM degeneration, inflammatory cytokine production, and NLRP3 inflammasome activation. However, in the presence of CAPE, DADS did not confer additional benefits in LPS-stimulated chondrocytes, suggesting that its effects are primarily mediated through the NF-κB/NLRP3 signaling pathway. In conclusion, DADS alleviates LPS-induced chondrocyte apoptosis, ECM degeneration, and inflammatory response by repressing the NF-κB/NLRP3 signaling pathway, providing a scientific basis for formulating DADS-based treatment strategies for OA.