Therapeutic evaluation of myricetin in experimental arthritis: modulation of inflammatory signaling and oxidative stress pathways.

Rheumatoid arthritis is a chronic, immune-mediated inflammatory disorder characterized by persistent synovial inflammation, progressive cartilage destruction, and bone erosion. Oxidative stress and excessive production of pro-inflammatory cytokines play central roles in its pathogenesis. Myricetin, a naturally occurring flavonoid, has gained attention for its anti-inflammatory and antioxidant properties. The present study evaluated the therapeutic potential of myricetin in complete Freund's adjuvant-induced arthritis in Wistar rats. Animals were randomly divided into six groups: control, arthritic control, methotrexate treated (0.5 mg/kg), and three myricetin treated groups (1, 2.5, and 5 mg/kg). Arthritis was induced in all experimental groups except the normal control by a single intra-articular injection of 0.2 ml CFA into the ankle joint of the left hind paw. Therapeutic intervention with methotrexate and the respective doses of myricetin was started on day 8 after induction and continued once daily for 21 consecutive days. Disease progression was assessed by body weight monitoring and arthritic scoring. Hematological parameters, rheumatoid factor, nitric oxide (NO), superoxide dismutase (SOD), and catalase levels were measured. The mRNA expression of IL-1β, IL-6, IL-17, TNF-α, and NF-κB was analyzed, and histopathological changes were examined using H&E staining. Myricetin significantly attenuated arthritic severity and leukocyte counts, enhanced antioxidant enzymes levels and downregulated the expression of pro-inflammatory cytokines and NF-κB. Histological findings further confirmed reduced synovial inflammation and attenuation of bone damage. These findings suggest that myricetin alleviates experimental arthritis, possibly through modulation of inflammatory mediators and oxidative stress pathways. However, further mechanistic and translational studies are required to establish its therapeutic efficacy and clinical relevance.