title: Anti-inflammatory effects of resveratrol, curcumin and simvastatin in acute small intestinal inflammation.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  Here 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.
  
  
  CONCLUSIONS
  Oral 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.
authors.affiliation: Institut für Mikrobiologie und Hygiene, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Bereswill
authors.forename: Melba
authors.initials: M
authors.lastname: Muñoz
authors.forename: André
authors.initials: A
authors.lastname: Fischer
authors.forename: Rita
authors.initials: R
authors.lastname: Plickert
authors.forename: Lea-Maxie
authors.initials: LM
authors.lastname: Haag
authors.forename: Bettina
authors.initials: B
authors.lastname: Otto
authors.forename: Anja A
authors.initials: AA
authors.lastname: Kühl
authors.forename: Christoph
authors.initials: C
authors.lastname: Loddenkemper
authors.forename: Ulf B
authors.initials: UB
authors.lastname: Göbel
authors.forename: Markus M
authors.initials: MM
authors.lastname: Heimesaat
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D003474:Curcumin / Q000494:pharmacology*; D004195:Disease Models, Animal; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D007079:Ileitis / Q000378:metabolism / Q000382:microbiology; D007249:Inflammation; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D000077185:Resveratrol; D019821:Simvastatin / Q000494:pharmacology*; D013267:Stilbenes / Q000494:pharmacology*; D018417:Th1 Cells / Q000187:drug effects; D014122:Toxoplasma / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D013267:Stilbenes; D019821:Simvastatin; D003474:Curcumin; D000077185:Resveratrol