Anti-arthritic activity of Ricinus communis L. and Withania somnifera L. extracts in adjuvant-induced arthritic rats via modulating inflammatory mediators and subsiding oxidative stress

Objective(s): This study aimed to evaluate the anti-arthritic activity of Ricinus communis leaves’ and Withania somnifera roots’ hydroalcoholic extracts in Complete Freund’s adjuvant-induced arthritis in Wistar rats. Materials and Methods: HPLC and FT-IR analysis detected pharmacologically important phytocompounds in both plant extracts. Oral treatments including methotrexate (MTX; ۳ mg/kg twice a week) and extracts at ۲۵۰ and ۵۰۰ mg/kg/day were initiated after arthritis induction. Changes in paw swelling, arthritic score, body weight, organ indices (thymus and spleen), hematological and biochemical parameters, and pro-/anti-inflammatory cytokine expression using qRT-PCR were assessed. Oxidative stress markers in hepatic tissue were determined. Histopathological and radiological examinations were also performed.  Results: RCE (R. communis extract) and WSE (W. somnifera extract) demonstrated a reduction in paw swelling, arthritic score, and restoration of body weight and organ indices. Hematological parameters, serum inflammatory markers such as CRP and RF, and liver function markers of arthritic rats were significantly (p <۰.۰۱) ameliorated with RCE and WSE treatment. Both plants persuasively down-regulated IL-۱β, IL-۶, IL-۱۷a, TNF-α, and RANKL and up-regulated IL-۴, INF-γ, and OPG relative expression as well as alleviating hepatic oxidative stress parameters. Histopathological and radiological findings revealed a marked reduction in tissue inflammation and bone erosion in extracts treated groups. Conclusion: The study findings suggest that R. communis leaves and W. somnifera roots have markedly subsided inflammation and improved health through modulating pro-/anti-inflammatory cytokine expression and reducing oxidative stress.

Keywords:

Antioxidants , Inflammatory cytokines , Oxidative stress , Rheumatoid arthritis , Ricinus communis , Withania somnifera