Amentoflavone inhibits iNOS, COX-2 expression and modulates cytokine profile, NF-κB signal transduction pathways in rats with ulcerative colitis

Abstract

Ulcerative colitis is a chronic inflammatory disorder characterized by oxidative stress, leucocyte infiltration and upregulation of pro-inflammatory cytokines. The aim of the present study was to examine the effect of amentoflavone on a murine model of ulcerative colitis (UC). UC was induced by intracolonic injection of 3% acetic acid in male Wistar rats. amentoflavone (10 mg/kg·b.wt) or reference drug sulfasalazine (100 mg/kg·b.wt) was administrated intra-peritoneally for 5 consecutive days before induction of colitis with acetic acid. Administration of amentoflavone was found to reduce the extent of inflammatory colonic injury. This was manifested by a decrease in the score of mucosal injury, by lowered colonic wet weight as well as vascular permeability and diminished lactate dehydrogenase (LDH) and myeloperoxidase (MPO) activity reflecting reduced leukocyte infiltration. Furthermore, the mucosal content of lipid peroxidation (LPO), glutathione (GSH), superoxide dismutase (SOD), nitric oxide (NO) activity confirms that amentoflavone could significantly inhibit colitis. The treatment also reduced significantly the colonic tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and IL-6 levels as well as the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) compared to colitis control group. The histopathological studies also confirm the foregoing findings. amentoflavone was also able to inhibit the activation and translocation of transcription factors, nuclear factor (NF)-κB subunits (p65/p50). These results suggest that amentoflavone exhibits protective effect in acetic acid-induced ulcerative colitis which might be due to its modulation of oxidant/anti-oxidant balance, down-regulation of productions and expressions of pro-inflammatory cytokines, inflammatory mediators and inhibition of NF-κB signal transduction pathways.

Keywords: Acetic acid; Amentoflavone; Cyclooxygenase-2 (COX-2); Inducible nitric oxide synthase (iNOS); Pro-inflammatory cytokines; Ulcerative colitis.