Potential anti-inflammatory action of resveratrol and piperine in adjuvant-induced arthritis: Effect on pro-inflammatory cytokines and oxidative stress biomarkers

Aim of the work: Resveratrol (RSV) is a phytoalexin with potent anti-inflammatory and anti-oxidant properties; however, its low bioavailability is considered a major obstacle. Piperine (PIP), an alkaloid, has been widely used as an effective bio-enhancer with drugs associated with low bioavailability. The current study was directed to examine the role of PIP in enhancing the efficacy of RSV in adjuvant-induced arthritis (AIA) in rats. Materials and methods: Carrageenan-induced paw edema model was designed for RSV and PIP doses optimization. Afterward, in the AIA model, rats were immunized at day 0 by sub-plantar injection of Freund’s complete-adjuvant. RSV (50 mg/kg) and PIP (20 mg/kg) were orally administered concurrently once daily from day 14 for two weeks. A standard anti-inflammatory drug, diclofenac, was employed for treatment validation. The paw volume was measured every 4 days. On day 29, rats were sacrificed and serum tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), thiobarbituric acid reactive substances (TBARS) and total nitrate/nitrite (NOx) were estimated. Ankles were dissected for histopathological examinations and immuno-histochemical expression of nuclear factor-kappa B p65 (NF-κB p65). Results: Co-administration of RSV and PIP significantly decreased the paw swelling and ameliorated the histopathological changes. In addition, the combined treatment highly reduced the serum TNF-α, IL-1β, TBARS and NOx. Besides, a nearly negative expression of NF-κB p65 in the synovial tissue was observed by co-administration of PIP with RSV. Results of the combination treatment were comparable to that of the diclofenac treatment. Conclusion: Co-administration of PIP enhanced the anti-inflammatory efficacy of RSV in the arthritic-induced rats. Keywords: Adjuvant-induced arthritis, Resveratrol, Piperine, Inflammation, Cytokines, Oxidative stress