Activation of Nrf2/HO-1 Signaling by Diallyl Disulfide Protects Chondrocytes from Lipopolysaccharide-Induced Apoptosis, Cartilage Degeneration, and Inflammation by Inhibiting the NF-κB/NLRP3 Inflammasome Signaling

Abstract

Osteoarthritis (OA) is a prevalent joint disorder characterized by the degradation of the extracellular matrix (ECM), destruction of cartilage and bone, and chronic inflammation. Diallyl disulfide (DADS), recognized for its anti-inflammatory, antioxidant, and anti-apoptotic properties, has not been previously assessed in the context of OA. This study aimed to explore the protective effects of DADS on lipopolysaccharide (LPS)-induced chondrocyte apoptosis, cartilage degeneration, and inflammation, as well as its underlying molecular mechanisms. Human chondrocytes were cultured in vitro, and an OA model was established through LPS stimulation. Various concentrations of DADS were analyzed to examine cell viability, apoptosis, ECM-related protein expression, levels of inflammatory cytokines, NLRP3 inflammasome activation, and NF-κB signaling. The results demonstrated that DADS alleviated LPS-induced chondrocyte injury and ECM degradation, suppressed inflammation and NLRP3 inflammasome activation, and inhibited LPS-induced NF-κB activation. Further analysis revealed that Nrf2 could play a crucial role in the protective effects of DADS against LPS-induced chondrocytes, in which DADS treatment activated the Nrf2/HO-1 pathway, and Nrf2 knockdown neutralized the protective effects of DADS. In conclusion, DADS could mitigate LPS-induced chondrocyte apoptosis, inflammatory cytokine secretion, and ECM degradation by activating the Nrf2/HO-1 signaling pathway in chondrocytes and simultaneously inhibiting the NF-κB signaling pathway and NLRP3 inflammasome activity. This research provided a promising therapeutic strategy for diseases associated with chondrocyte injury.