Farrerol ameliorate adjuvant‐induced ankle injury via alteration of PPAR‐γ signal pathway

Abstract

This study evaluated the anti-inflammatory activity against lipopolysaccharide (LPS)-mediated mouse macrophages (in vitro) and assessed the protective effect of farrerol on arthritis caused by complete freund adjuvant (CFA) in rats. For the evaluation of the pharmacological effect of farrerol on the activity of nitric oxide (NO) and cyclooxygenase, pro-inflammatory cytokines including interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interleukin-1β, RAW 264.7 cells were used. A 0.1ml CFA was injected subcutaneously for the induction of arthritis. The paw volume, body weight and arthritic score were estimated at regular intervals. Pro-inflammatory cytokines, inflammatory mediators, and antioxidant parameters were also estimated. Farrerol suppressed NO production and COX-catalyzed prostaglandin (PGE2 ) in RAW 264.7. Farrerol also downregulated the p-p65, p-IκBα expression and upregulated the PPAR-γ expression in RAW 264.7 cells. Treatment of farrerol increased body weight substantially, and reduced paw edema and arthritic score. Farrerol treatment also significantly improved the level of hemoglobin (Hb), count of red blood cells (RBC), and decreased the rate of erythrocyte sedimentation (ESR), white blood cell (WBC) parameters, while the generation of pro-inflammatory cytokines inhibited. Together, farrerol also suppressed the pro-inflammatory cytokines TNF-α, IL-6, and IL-1β. Obtained results directed that the farrerol exerted its therapeutic effect against CFA-induced arthritic rats through anti-inflammatory mechanism by regulation of the PPAR-γ. PRACTICAL APPLICATIONS: Increase the arthritis disease worldwide day-by-day. The current research study showed the anti-arthritic effect of farrerol (flavonoid phytoconstituent) of Rhododendron dauricum Linn. In this study, farrerol considerably inhibited the NF-κB to show the anti-arthritic effect. The finding showed the potential effect against acute and chronic inflammation via inhibition of inflammatory mediators and oxidative stress. The result suggests the anti-inflammatory and antioxidant effect of farrerol. On the basis of result, we can say that farrerol can be the beneficial drug to treat the arthritis.