Immunomodulatory effects of ononin alleviates arthritis through modulation of macrophage polarization and JAK/STAT3 signaling.

Arthritis is an inflammatory disease characterized by synovial inflammation and joint destruction. Macrophages play a crucial role in the pathogenesis of arthritis by adopting pro-inflammatory M1 or anti-inflammatory M2 phenotypes. Ononin, a flavonoid compound, has shown potential immunomodulatory effects in various inflammatory conditions. This study aimed to investigate the impact of ononin on macrophage polarization in a monosodium iodoacetate (MIA)-induced animal model of arthritis. MIA was utilized to induce arthritis in animal models. RAW 264.7 macrophages were treated with Lipopolysaccharide (LPS), IL-4, ononin, and tofacitinib alone or in combination to evaluate their effects on macrophage polarization. Laser confocal microscopy and flow cytometry were used to assess the expression levels of JAK, STAT3, M2-specific marker CD206, and M1-specific marker CD86 in macrophages under various treatment conditions. Ononin treatment significantly improved joint function in rats, as evidenced by histological analysis showing reduced inflammation, cartilage degradation, and osteoclast activity. Additionally, ononin treatment significantly upregulated CD206 expression, indicative of M2 macrophage polarization. Furthermore, laser confocal microscopy revealed that IL-4 and ononin increased JAK/STAT3 expression, highlighting their immunomodulatory effects. Co-treatment with ononin and LPS showed a suppressive effect on JAK/STAT3 signaling, which was completely inhibited by tofacitinib in cultured RAW 264.7. Ononin exhibits immunomodulatory effects by driving macrophage polarization towards the anti-inflammatory M2 phenotype, potentially alleviating the symptoms of arthritis in MIA-induced animal models. The modulation of JAK/STAT3 signaling by ononin underscores its therapeutic potential in the treatment of arthritis.