Tangeretin ameliorates osteoarthritis and suppresses synovial macrophage M1 polarization in association with suppression of NF-κB signaling

Osteoarthritis (OA) is a chronic, degenerative joint disease that carries significant economic and clinical impacts. M1 polarization of synovial macrophages exacerbates synovitis progression, and thus, targeting M1 macrophage inhibition emerges as a promising therapeutic strategy for OA. Although Tangeretin exhibits anti-inflammatory properties, its impact on OA and the associated mechanisms remain unelucidated. Techniques such as in vitro ELISA, Western blot analysis, and immunofluorescence staining were employed to assess Tangeretin’s influence on macrophage M1 polarization and chondrocyte metabolism. Conversely, histopathological analysis and immunohistochemical staining were utilized to evaluate Tangeretin’s in vivo therapeutic effects on synovial inflammation and cartilage degeneration. Tangeretin was found to inhibit IL-1β-mediated secretion of inflammatory mediators and mitigate ECM degradation in chondrocytes. Additionally, attenuation of M1 macrophage polarization by Tangeretin was accompanied by suppression of the NF-κB signaling. Furthermore, Tangeretin decreased IL-1β and MMP13 levels in the conditioned medium of M1 macrophages, consequently enhancing glycosaminoglycan (GAG) synthesis in chondrocytes. In vivo, Tangeretin alleviated iodoacetic acid-induced cartilage degeneration and M1 macrophage polarization in the synovium. These findings indicate that Tangeretin inhibits OA progression by suppressing M1 macrophage polarization in association with suppression of NF-κB signaling pathway, suggesting its potential as an effective OA treatment.