Abstract / Summary
Abstract Osteoarthritis (OA) is a progressive joint disease characterized by cartilage destruction and is increasingly recognized as involving chronic low-grade inflammation. Synovitis contributes to OA progression through the production of proinflammatory mediators and reactive oxygen species (ROS). Sesamin, a lignan derived from sesame seeds, has demonstrated antioxidant and anti-inflammatory activities in various experimental models. However, the integrated effects of sesamin on oxidative stress, the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) pathway, and NLRP3 expression in interleukin-1β (IL-1β)-stimulated human synoviocytes remain insufficiently characterized. This study investigated the effects of sesamin on oxidative stress and inflammatory responses and examined the involvement of the Nrf2/HO-1 pathway and NLRP3 expression in IL-1β-stimulated human SW982 synovial cells. Sesamin (2.5–10 μM) significantly reduced IL-1β-induced intracellular ROS levels, with a 60% reduction observed at the highest concentration. At 10 μM, sesamin increased Nrf2 nuclear translocation approximately 2-fold and HO-1 expression by 1.5-fold compared with the IL-1β control. In contrast, sesamin reduced NLRP3 expression to approximately 0.5-fold of the IL-1β control. Sesamin also reduced the levels of IL-1β, IL-6, and cyclooxygenase-2 (COX-2) by approximately 50%, 12%, and 40%, respectively. These findings demonstrate that sesamin attenuates IL-1β-induced oxidative and inflammatory responses in human synovial cells, accompanied by activation of the Nrf2/HO-1 antioxidant pathway and reduced NLRP3 expression. Collectively, these findings support further investigation of sesamin as a potential therapeutic modulator of synovitis-associated mechanisms in OA.