Therapeutic activity of N‐(2‐hydroxy phenyl) acetamide: a novel anti‐arthritic agent on pro‐inflammatory cytokines production and suppression of Toll‐like receptors (TLR‐2 and TLR‐4) in adjuvant‐induced arthritic rats

Abstract

Toll‐like receptors (TLRs) are key recognition structures of immune system and emerged as potential contributors to the inflammation observed in human and rodent models of arthritis. In addition, the pro‐inflammatory cytokines IL‐1β and TNF‐α play an important role in aggravating the disease process. Present study aims to investigate the effect of N‐(2‐hydroxy phenyl)‐acetamide (NA‐2) on modulation of TLRs in the development of adjuvant‐induced arthritis. Arthritis was induced by heat‐killed MT H37Ra. Treatment of NA‐2 (5 mg/kg) was started on the day of arthritis induction. Body weights, paw volume and nociception measurements were done to monitor the progression of the disease. TLR‐2 and TLR‐4 mRNAs were analyzed in 48‐h cultured splenocytes and the supernatants were used to determine IL‐1β and TNF‐α. A significant increase in body weights with a parallel decrease in paw edema and nociception was observed in NA‐2 treated animals. Remission of the clinical signs was associated with improved histology. NA‐2 treatment significantly decreased the level of IL‐1β (p < 0.003) and TNF‐α (p < 0.001). Likewise, NA‐2 also reduced the expression of TLRs mRNA. Our findings suggest that NA‐2 affects AIA in a pleiotropic manner, suppressing TLRs‐mediated joint inflammation and thus it might have a therapeutic potential for arthritis