Prophylactic effect of aquatic extract of stevia on acetic acid induced-ulcerative colitis in male rats: a possible role of Nrf2 and PPARγ

J Basic Clin Physiol Pharmacol. 2020 Oct 12;32(6):1093-1104. doi: 10.1515/jbcpp-2020-0039.


Objectives: Ulcerative colitis (UC) is a non-specific intestinal inflammatory disease. Several studies demonstrated that inflammation and oxidative stress play significant role in the pathogenesis of this disease. This study aimed to determine the protective effect and possible mechanism by which stevia affects the course of experimentally induced colitis.

Methods: Male rats were received stevia 20, 40, 80 mg/kg/day before induction of colitis by intra-rectal administration of 2 mL of 4% acetic acid, AA. Macroscopic and histopathological examination of the colon were done. Colonic content of catalase (CAT), superoxide dismutase (SOD), reduced glutathione (GSH), myeloperoxidase (MPO) and thiobarbituric acid reactive substances (TBARS) activities and serum levels of interleukin (IL)1- β and tumor necrosis factor (TNF)-α were assessed. Real time-PCR (RT-PCR) was done to determine the expression of NF-κB, Nrf2 and PPARγ genes. Spontaneous contraction and effects of increasing concentrations of acetylcholine and stevia have been studied on the isolated colonic segments.

Results: Stevia ameliorated colitis not only histopathologically but also it decreased the level of TNF-α, IL-1β, TBARS, MPO and the expression of NF-κB which were significantly increased in the AA group. The concentration of GSH, SOD, CAT and expression of Nrf2 and PPARγ were significantly increased with stevia. Moreover, stevia showed a relaxant effect on the colonic contractility which was increased in AA group. These all effects of stevia were more prominent with its highest dose.

Conclusion: Our results explored that, stevia acts protectively against UC by its anti-inflammatory and antioxidant properties which mediated by up-regulation of Nrf2 and PPARγ with downregulation of NF-κB. We suggest that stevia has the potential for treatment of chronic inflammatory diseases, such as UC.

Keywords: NF-κB; Nrf2; PPARγ; colonic contractility; oxidative stress; ulcerative colitis (UC).

MeSH terms

  • Acetic Acid
  • Animals
  • Colitis, Ulcerative* / chemically induced
  • Colitis, Ulcerative* / drug therapy
  • Colon / drug effects
  • Male
  • NF-E2-Related Factor 2 / metabolism*
  • NF-kappa B
  • PPAR gamma / metabolism*
  • Plant Extracts* / pharmacology
  • Rats
  • Stevia* / chemistry
  • Superoxide Dismutase
  • Thiobarbituric Acid Reactive Substances
  • Tumor Necrosis Factor-alpha


  • NF-E2-Related Factor 2
  • NF-kappa B
  • Nfe2l2 protein, rat
  • PPAR gamma
  • Plant Extracts
  • Thiobarbituric Acid Reactive Substances
  • Tumor Necrosis Factor-alpha
  • Superoxide Dismutase
  • Acetic Acid