Ameliorative Potential of Kaempferol in TNBS-Induced Colitis in Experimental Rats: A Role of Activation of PPARγ Pathway

Chenhui Huang and Jiaqi Hu

Background and Objective: Ulcerative colitis (UC) is a chronic condition mainly characterized by inflammatory and ulcerative interstitial mucosa of the colon. Kaempferol has been reported for its antioxidant, antiinflammation, antiulcer and wound healing effects. The objective of the study was to evaluate the potential of kaempferol against UC induced by Trinitrobenzene Sulfonic Acid (TNBS) in experimental rats. Materials and Methods: The TNBS (100 mg/kg, in 50% ethanol) was used to induce colitis in overnight fasted Sprague-Dawley rats (180-220 g) on day 0 and they received (n = 18, in each group) either vehicle (DMSO) or 5-aminosalicylic acid (500 mg/kg), or kaempferol (50 or 100 or 200 mg/kg), orally for 14 days. Various macroscopic, biochemical, molecular and histopathological analysis was assessed to evaluate the efficacy of kaempferol against UC. Results: The TNBS-induced spleen enlargement, colonic damage and ulceration were effectively and dose-dependently (p<0.01 and p<0.001) ameliorated by kaempferol (100 and 200 mg/kg). Elevated colonic oxido-nitrosative (SOD, GSH, MDA and nitric oxide) stress and MPO levels were also markedly (p<0.01 and p<0.001) reduced by kaempferol treatment. The TNBS-induced elevated cytokine levels (TNF-α and IL-1β) were significantly (p<0.01 and p<0.001) decreased after kaempferol administration. Western blot analysis also suggested that altered colonic PPARγ and collagen-1 protein expressions were effectively (p<0.01 and p<0.001) down-regulated by kaempferol administration. Furthermore, kaempferol treatment markedly reduced histopathological alteration induced by TNBS in the colon (p<0.01 and p<0.001). Conclusion: The results of the present study suggested that kaempferol exerts its colono-protective effect via activation of the PPARγ pathway to inhibit the release of inflammatory cytokines, oxidative stress, neutrophil infiltration and collagen-1 formation during TNBS-induced colitis.

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