Allyl Methyl Sulfone Attenuates Oxidative Stress and Inflammation in Fibroblast-Like Synoviocytes via NF-Κb P65/SLC7A11 Signaling iin Osteoarthritis

Abstract

Allyl methyl sulfone (AMSO₂) is an oxidative metabolite derived from allyl methyl sulfide, a major garlic component. AMSO₂ has been demonstrated to exert anti-inflammatory and antioxidative effects; however, its effect on arthritis has not yet been thoroughly studied. Overactivation and uncontrolled proliferation of synoviocytes are the major causes of arthritis progression, which is characterized by persistent inflammation. In the present study, we found that AMSO₂ could alleviate the osteoarthritis (OA) progression in mice models, and inhibit inflammatory response in tumor necrosis factor α (TNFα)-stimulated human fibroblast-like synoviocytes (FLSs) by suppressing the expression of cytokines and chemokines, such as C–C motif chemokine ligand 2 (CCL2), interleukin (IL)-6, interleukin (IL)-8. AMSO₂ also reduced oxidative stress by downregulating the expression of inducible nitric oxide synthase (iNOS) and inhibiting the production of reactive oxygen species (ROS). Furthermore, the expression and secretion of matrix metalloproteinases were significantly reduced by AMSO₂. This study also showed that the effect of AMSO₂ on FLSs was exerted through the nuclear factor kappa-B (NF-κB) signaling pathways, with SLC7A11 and glutathione peroxidase 4 (GPX4) being the downstream factors. Overall, these findings indicate that AMSO₂ regulates synovial inflammation in arthritis, thereby serving as a potential target for arthritis treatment.