Abstract
Inflammatory bowel disease (IBD) is a chronic, relapsing, and tissue-destructive disease. Resveratrol (3,4,5-Trihydroxy-trans-stilbene), a naturally occurring polyphenol that exhibits beneficial pleiotropic health effects, is recognized as one of the most promising natural molecules in the prevention and treatment of chronic inflammatory disease and autoimmune disorders. In the present study we investigated the effect of resveratrol on dextran sodium sulphate (DSS)-induced colitis in mice, finding that it effectively attenuated overall clinical scores as well as various pathological markers of colitis. Resveratrol reversed the colitis-associated decrease in body weight and increased levels of serum amyloid A (SAA), TNF-α, IL-6, and IL-1β. After resveratrol treatment, the percentage of CD4+T cells in mesenteric lymph nodes (MLNs) of colitis mice was restored to normal levels and there was a decrease in these cells in the intestinal lamina propria (LP). Similarly, the percentages of macrophages in MLNs and the LP of mice with colitis were decreased after resveratrol treatment. Resveratrol also suppressed COX-2 expression induced in DSS-exposed mice. Colitis was associated with a decrease in silent mating type information regulation-1 (SIRT1) gene expression and an increase in p-IκBα expression and NF-κB activation. Interestingly, resveratrol treatment of mice with colitis significantly reversed these changes. This study demonstrates for the first time that SIRT1 is involved in colitis, functioning as an inverse regulator of NF-κB activation and inflammation. Furthermore, our results indicate that resveratrol may protect against colitis through up-regulation of SIRT1 in immune cells in the colon.
Footnotes
- Received August 20, 2009.
- Revision received November 24, 2009.
- Accepted November 24, 2009.
- The American Society for Pharmacology and Experimental Therapeutics