Sinomenine contributes to the inhibition of the inflammatory response and the improvement of osteoarthritis in mouse-cartilage cells by acting on the Nrf2/HO-1 and NF-κB signaling pathways

Pathological changes, such as articular cartilage degeneration, destruction, and hyperosteogeny, are regarded as the main features of osteoarthritis (OA). Sinomenine (SIN) is a monomeric component purified from the plant Sinomenium acutum which has been found to have anti-inflammatory effects, however, the mechanism of action of SIN on OA is not clear. In this study, we evaluated whether SIN could regulate the inflammatory response induced by interleukin (IL)-1 beta and improve outcomes in the instability model of OA (medial meniscus mice (DMM)) by acting on the Nrf2/HO-1 and NF-kappa B signaling pathways in chondrocytes. From our experiments, which include Griess reaction, ELISA, Western blot, and immunofluorescence, we found that SIN not only down-regulated the expression of pro-inflammatory factors induced by IL-1 beta, including; inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), nitricoxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor alpha (TNF-a) and interleukin-6 (IL-6), but also decreased the production of IL-1 beta-induced cartilage matrix catabolic enzymes including; ADAMTS-5 and MMPs, in mouse chondrocytes. In addition, the degradation of aggrecan and type II collagen protein in the extracellular matrix (ECM) stimulated by IL-1 beta was reversed. Most importantly, we have revealed for the first time that in OA, SIN inhibited the inflammatory response and ECM degradation by activating the Nrf2/HO-1 signaling pathways and inhibiting NF-kappa B activity in mouse-cartilage cells. In in vivo experiments, SIN treatment helped to improve the cartilage destruction in OA model mice. In conclusion, this study has demonstrated that SIN inhibits the IL-1 beta-induced inflammatory response and cartilage destruction by activating the Nrf2/HO-1 signaling pathway and inhibiting the NF-kappa B signaling pathway in mouse chondrocytes, suggesting a new use for SIN in the treatment of OA.