Tangeretin Suppresses Osteoarthritis Progression Via the Nrf2/NF-κB and MAPK/NF-κB Signaling Pathways

Background: Osteoarthritis (OA) is a globally prevalent degenerative disease characterized by extracellular matrix (ECM) degradation and inflammation. Tangeretin is a natural flavonoid that has anti-inflammatory properties. Studies have not explored whether tangeretin modulates OA development.

Purpose: The aim of this study was to explore the potential effects and mechanism underlying the anti-OA properties of tangeretin.

Study Design: Effects of tangeretin on OA were detected in chondrocytes and OA mouse model.

Methods: Protective effects of tangeretin on murine articular chondrocytes treated with interleukin-1β (IL-1β) were evaluated using qPCR, western blot analysis, ELISA, ROS detection and immunofluorescent staining in vitro. Healing effect of tangeretin on cartilage degradation in mice was assessed through X-ray imaging, histopathological analysis, immunohistochemical staining and immunofluorescent staining in vivo.

Results: Tangeretin suppressed IL-1β-mediated inflammatory mediator secretion and degradation of ECM in chondrocytes. The results showed that tangeretin abrogated destabilized medial meniscus (DMM)-induced cartilage degradation in mice. Mechanistic studies showed that tangeretin suppressed OA development by downregulating activation of NF-κB by activating Nrf2/HO-1 axis and suppressing MAPK signaling pathway.

Conclusion: Tangeretin abrogates OA progression by inhibiting inflammation as well as ECM degradation in chondrocytes and animal models. Effects of tangeretin are mediated through Nrf2/NF-κB and the MAPK/NF-κB pathways. Thus, tangeretin is a potential therapeutic agent for osteoarthritis treatment.