Fisetin Attenuates Cartilage Destruction in Adjuvant-Induced Arthritis by Modulating Cartilage Cytokine Expression Correlated with Oxidative Status in the Early Phase in Experimental Animals

The present study was designed to evaluate the effect of Fisetin on the progression of adjuvant-induced arthritis in rats and explore the mechanisms underlying fisetin mediated immunomodulation. Adjuvant-induced arthritis (AIA) was induced by a single subcutaneous injection of Freund's complete adjuvant (FCA). AIA rats were treated with Fisetin daily via oral gavage, for a period of 28 days. Paw swelling changes were assessed and histopathological and radiographic analysis was conducted to evaluate the antiarthritic effect. Lipid peroxidation and antioxidant enzyme activities in the joint tissue homogenate were performed to observe the modulation of the antioxidant status along the expression of different pro-inflammatory cartilage cytokines, such as TNF-á and IL-6. Fisetin promotes both the antiarthritic and the antioxidant effect, as well as the suppression of lipid peroxidation. Fisetin significantly inhibited the development phase of arthritis, as supported by histopathological and radiographical observations, and reduced overexpression of cartilage cytokines. Fisetin not only suppressed the arthritic progression and tissue destruction, but it also demonstrated a pronounced anti-inflammatory and immunomodulatory action against the immunosuppressive properties of AIA and provided a superior effect against inflammation. Furthermore, fisetin therapy restored the BMD loss and acts as a potent antioxidant and immunomodulator, suggesting that oral administration can suppress arthritic progression in rats.