Dietary supplementation of resveratrol attenuates chronic colonic inflammation in mice.
Ulcerative colitis is a nonspecific inflammatory disorder characterized by oxidative and nitrosative stress, leucocyte infiltration and upregulation of inflammatory mediators. Resveratrol is a polyphenolic compound found in grapes and wine, with multiple pharmacological actions, mainly anti-inflammatory, antioxidant, antitumour and immunomodulatory activities. The aim of this study was to investigate the effect of dietary resveratrol on chronic dextran sulphate sodium (DSS)-induced colitis. Six-week-old mice were randomized into two dietary groups: one standard diet and the other enriched with resveratrol at 20mg/kg of diet. After 30days, mice were exposed to 3% DSS for 5days developing acute colitis that progressed to severe chronic inflammation after 21days of water. Our results demonstrated that resveratrol group significantly attenuated the clinical signs such as loss of body weight, diarrhea and rectal bleeding improving results from disease activity index and inflammatory score. Moreover, the totality of resveratrol-fed animals survived and finished the treatment while animals fed with standard diet showed a mortality of 40%. Three weeks after DSS removal, the polyphenol caused substantial reductions of the rise of pro-inflammatory cytokines, TNF-alpha and IL-1beta and an increase of the anti-inflammatory cytokine IL-10. Also resveratrol reduced prostaglandin E synthase-1 (PGES-1), cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) proteins expression, via downregulation of p38, a mitogen-activated protein kinases (MAPK) signal pathway. We conclude that resveratrol diet represents a novel approach to the treatment of chronic intestinal inflammation.
Department of Pharmacology, School of Pharmacy, University of Seville, Spain. fidalgo@us.es
Susana
S
Sánchez-Fidalgo
Ana
A
Cárdeno
Isabel
I
Villegas
Elena
E
Talero
Catalina Alarcón
CA
de la Lastra
D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D002908:Chronic Disease; D003093:Colitis, Ulcerative / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D003106:Colon / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D016264:Dextran Sulfate; D019587:Dietary Supplements; D004195:Disease Models, Animal; D005260:Female; D019746:Intramolecular Oxidoreductases / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D000071876:Prostaglandin-E Synthases; D011897:Random Allocation; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects; D013267:Stilbenes / Q000008:administration & dosage*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D013267:Stilbenes; D016264:Dextran Sulfate; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D048051:p38 Mitogen-Activated Protein Kinases; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases; D000077185:Resveratrol