Abstract
BackgroundThe health beneficial effects of Resveratrol, Curcumin and Simvastatin have been demonstrated in various experimental models of inflammation. We investigated the potential anti-inflammatory and immunomodulatory mechanisms of the above mentioned compounds in a murine model of hyper-acute Th1-type ileitis following peroral infection with Toxoplasma gondii.Methodology/Principal FindingsHere we show that after peroral administration of Resveratrol, Curcumin or Simvastatin, mice were protected from ileitis development and survived the acute phase of inflammation whereas all Placebo treated controls died. In particular, Resveratrol treatment resulted in longer-term survival. Resveratrol, Curcumin or Simvastatin treated animals displayed significantly increased numbers of regulatory T cells and augmented intestinal epithelial cell proliferation/regeneration in the ileum mucosa compared to placebo control animals. In contrast, mucosal T lymphocyte and neutrophilic granulocyte numbers in treated mice were reduced. In addition, levels of the anti-inflammatory cytokine IL-10 in ileum, mesenteric lymph nodes and spleen were increased whereas pro-inflammatory cytokine expression (IL-23p19, IFN-γ, TNF-α, IL-6, MCP-1) was found to be significantly lower in the ileum of treated animals as compared to Placebo controls. Furthermore, treated animals displayed not only fewer pro-inflammatory enterobacteria and enterococci but also higher anti-inflammatory lactobacilli and bifidobacteria loads. Most importantly, treatment with all three compounds preserved intestinal barrier functions as indicated by reduced bacterial translocation rates into spleen, liver, kidney and blood.Conclusion/SignificanceOral treatment with Resveratrol, Curcumin or Simvastatin ameliorates acute small intestinal inflammation by down-regulating Th1-type immune responses and prevents bacterial translocation by maintaining gut barrier function. These findings provide novel and potential prophylaxis and treatment options of patients with inflammatory bowel diseases.
Highlights
Several nutritional compounds are the focus of public attention because of their potential beneficial health effects
Whereas all untreated control mice had died at day 11 p.i., 20% of Curcumin- and 40% of Simvastatin- or Resveratrol-treated animals survived the acute phase of inflammation (Fig. 1)
Mice orally treated with Simvastatin, Resveratrol or Curcumin displayed significantly less macroscopic signs of intestinal inflammation
Summary
Several nutritional compounds are the focus of public attention because of their potential beneficial health effects. Some compounds derived from plants and herbs (e.g. Resveratrol, Curcumin) have been proven effective in traditional medicine as herbal remedies for inflammatory disorders such as hepatitis, arthritis, and colitis [1]. Resveratrol and Curcumin exert pharmacological effects in various experimental models of acute and chronic inflammation [1]. Resveratrol has been reported to exert multiple health-promoting benefits such as anti-inflammatory, anti-oxidant, anti-tumor, anti-platelet aggregation, antiaging and anti-atherogenic effects [3]. Anti-inflammatory properties of Resveratrol have been described in several diseases such as arthritis [4], pancreatitis [5], and experimental colitis [6]. The health beneficial effects of Resveratrol, Curcumin and Simvastatin have been demonstrated in various experimental models of inflammation. We investigated the potential anti-inflammatory and immunomodulatory mechanisms of the above mentioned compounds in a murine model of hyper-acute Th1-type ileitis following peroral infection with Toxoplasma gondii
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