Exploration of molecular mechanisms responsible for arthritis alleviating attributes of Calliandra haematocephala extracts

Inflammation and autoimmunity create a complex array of pathological parameters to induce rheumatoid arthritis (RA) that is primarily a disease of the musculoskeletal system. To date, there is no cure for RA. The purpose of the present study was to evaluate the antiarthritic effects of n-Hexane (CHnHE) and methanolic (CHME) extracts of Calliandra haematocephala in Complete Freund’s adjuvant-induced (CFA) arthritis. For this purpose, 30 mg/kg Naproxen and 3 doses of C. haematocephala extracts (250, 500 and 750 mg/kg) were administered to Wistar rats immunised with CFA. To evaluate the antiarthritic effects, the assessment parameters included paw swelling, arthritic index, changes in body and immune organ weights, haematological indices, biochemical markers, oxidative stress markers, radiographic and histopathological evaluation of paws, and mRNA expression analysis. Results of the study revealed significant (p < 0.05)  improvement in disease parameters in contrast to the arthritic control group. Both extracts attenuated paw inflammation and restored the whole body and immune organ weights. Haematological and biochemical derangements were significantly improved in the extract treated animals. Serum levelsof antioxidant enzymes were increased, whereas malondialdehyde (MDA) level was decreased in the extract treated animals. Radiographic and histopathological examination of paws revealed that both extracts prevented synovitis, pannus formation and bone erosion. RT-qPCR analysis revealed the downregulation of pro-inflammatory mediators and upregulation of anti-inflammatory cytokines in the extract treated rats. Phytochemical analysis exhibited the presence of phenolic acids, flavonoids, terpenoids, sterols and tannins in both extracts. On the basis of the findings of the present study, it is proposed that CHnHE  and CHME possess noticeable antiarthritic activity possibly via modulation of the immune system and antioxidant defense mechanisms.