Nebivolol ameliorates CFA-induced adjuvant arthritis and is associated with reduced WNT5A and active β-catenin protein levels

Abstract Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disorder characterized by synovial inflammation, cartilage destruction, bone erosion, and progressive functional impairment. Despite therapy, treatment failure and adverse effects remain major challenges. This study investigated the repurposing of nebivolol, a selective β1-adrenergic receptor blocker, against Complete Freund’s Adjuvant (CFA)-induced rheumatoid arthritis in Wistar rats. CFA-induced inflammatory arthritis was induced by subcutaneous injection of CFA into the plantar surface of the left hind paw. Nebivolol was administered orally (5 and 10 mg/kg). Paw edema, arthritis score, and macroscopic & histopathological alterations were evaluated. Inflammatory biomarkers including tumor necrosis factor-alpha (TNF-α), nuclear factor-kappa B (NF-κB), rheumatoid factor (RF), Wnt, and β-catenin were assessed. CFA induced marked arthritic manifestations, including paw swelling, increased arthritis scores, inflammatory cell infiltration, histopathological joint damage, and elevated RF, TNF-α, NF-κB, Wnt5A, and active β-catenin levels. Nebivolol significantly reduced paw edema, arthritis severity, inflammatory biomarkers, and improved macroscopic & histopathological findings. Furthermore, nebivolol treatment ameliorated arthritis and was associated with reduced Wnt5A and active β-catenin protein levels. Nebivolol demonstrated significant anti-inflammatory effects against CFA-induced adjuvant arthritis. These findings support its potential as a repurposed therapeutic candidate for RA through modulation of inflammation and Wnt and β-catenin protein levels.