Fisetin, a dietary flavonoid, ameliorates experimental colitis in mice: Relevance of NF-κB signaling

Fisetin, a dietary flavonoid, is commonly found in many fruits and vegetables. Although studies indicate that fisetin has an anti-inflammatory property, little is known about its effects on intestinal inflammation. The present study investigated the effects of the fisetin on dextran sulphate sodium (DSS)-induced murine colitis, an animal model that resembles human inflammatory bowel disease. Fisetin treatment to DSS-exposed mice significantly reduced the severity of colitis and alleviated the macroscopic and microscopic signs of the disease. Moreover, fisetin reduced the levels of myeloperoxidase activity, the production of proinflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (1L-1 beta) and interleukin-6 (IL-6) and the expressions of COX-2 and iNOS in the colon tissues. Further studies revealed that fisetin suppressed the activation of NF-kappa B (p65) by inhibiting I kappa B alpha phosphorylation and NF-kappa B (p65) DNA binding activity and attenuated the phosphorylation of Akt and the p38, but not ERK and JNK MAPKs in the colon tissues of DSS-exposed mice. In addition, DSS-induced decline in reduced glutathione (GSH) and the increase in malondialdehyde (MDA) levels were significantly restored by oral fisetin. Furthermore, the results from in vitro studies showed that fisetin significantly reduced the pro-inflammatory cytokine and mediator release and suppressed the degradation and phosphorylation of I kappa B alpha with subsequent nuclear translocation of NF-kappa B (p65) in lipopolysaccharide (LPS)-stimulated mouse primary peritoneal macrophages. These results suggest that fisetin exerts anti-inflammatory activity via inhibition of Akt, p38 MAPK and NF-kappa B signaling in the colon tissues of DSS-exposed mice. Thus, fisetin may be a promising candidate as pharmaceuticals or nutraceuticals in the treatment of inflammatory bowel disease. (C) 2015 Elsevier Inc. All rights reserved.