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Taming the beast within: resveratrol suppresses colitis and prevents colon cancer

Lorne J. Hofseth, Singh, U.P., Narendra P. Singh, Mitzi Nagarkatti, and Prakash S. Nagarkatti (2010) Taming the beast within: resveratrol suppresses colitis and prevents colon cancer. Aging 2(4): 183-184.

Abstract

Resveratrol has generated extensive scientific and public interest in recent years mainly because of its ability to delay aging and prevent age-related diseases. Mild-to-moderate red wine consumption has anti-inflammatory properties, and can reduce the risk of cardiovascular disease and cancer. The resveratrol content in red wine is often cited to account for this “French paradox”. There is increasing literature suggesting that resveratrol may have anti-aging properties through the activation of silent mating type information regulation-1 (SIRT-1) [1]. We have now shown that inflammation in the colon down-regulates SIRT-1 and enhances nuclear transcription factor-kappaB (NF-κB) while resveratrol reverses this process [2]. We showed the efficacy of resveratrol in a dextran sodium sulfate (DSS)- mouse as well as in a spontaneous IL-10-/- mouse model of colitis.
Specifically, in this as well as our other study [3], we found that resveratrol attenuated overall clinical scores as well as various pathological markers of colitis. Resveratrol reversed colitis-associated decreased body weight and colon length; and suppressed colitis-induced inflame-matory markers (iNOS, COX-2, TNF-α) and markers of inflammatory stress (p53 and phosphor-p53-serine 15). Also, resveratrol suppressed the activation of CD3+ T helper cells, and reversed DSS-mediated increases in serum amyloid A, TNF-α, interleukin (IL-6), and IL-1β. After resveratrol treatment, the percentage of neutrophils, and CD4+ T cells in mesenteric lymph nodes (MLN) of colitis mice was restored to normal levels, and there was a decrease in these cells in the colon lamina propria (LP). Likewise, the percentages of macrophages and neutrophils in MLN and the LP of mice with colitis were decreased after resveratrol treatment. Our studies demonstrated for the first time that SIRT-1 is involved in colitis, functioning as an inverse regulator of NF-κB activation and inflammation.

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