Resveratrol (Trans-3,5,4′-trihydroxystilbene) Induces Silent Mating Type Information Regulation-1 and Down-Regulates Nuclear Transcription Factor-κB Activation to Abrogate Dextran Sulfate Sodium-Induced Colitis

Abstract

Inflammatory bowel disease is a chronic, relapsing, and tissuedestructive 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 sulfate (DSS)-induced colitis in mice and found 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, tumor necrosis factor-␣, interleukin (IL-6), and IL-1␤. After resveratrol treatment, the percentage of CD4 ϩ 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 in MLN and the LP of mice with colitis were decreased after resveratrol treatment. Resveratrol also suppressed cyclooxygenase-2 (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-inhibitory B expression and nuclear transcription factor-B (NF-B) activation. 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-B activation and inflammation. Furthermore, our results indicate that resveratrol may protect against colitis through up-regulation of SIRT1 in immune cells in the colon.

Resveratrol Improves Cardiac Contractility following Trauma-Hemorrhage by Modulating Sirt1

“…Though most reports on the mechanism of RSV-induced biological effects focused on its allosteric effect on Sirt1 leading to increased enzymatic activity, RSV is also reported to increase the expression of Sirt1 through unknown mechanisms (42). It is possible that enhanced Sirt1 expression, along with increased activity, may further augment recovery or Sirt1 upregulation and this may be the primary mechanism of RSV-mediated salutary effect.…”

Microbial Links to Inflammatory Bowel Disease Development: Potential Interventional Strategies in Treatment

“…Treatment with polyphenol has also been shown to prevent or delay the progression of IBD [40]. We have reported that orally administered resveratrol ameliorates both dextran sodium sulphate (DSS)-induced and IL-10 -/-chronic colitis in mice [41,42]. Our studies suggest that resveratrol targets multiple signaling pathways, including silent mating type information regulation-1 (SIRT1) gene expression, which has not been previously investigated with regard to its association with colitis.…”

“…Our studies suggest that resveratrol targets multiple signaling pathways, including silent mating type information regulation-1 (SIRT1) gene expression, which has not been previously investigated with regard to its association with colitis. To this end, colitis induction may downregulate SIRT1 levels and promote both NF-kB activation and cytokine expression in the colon, and resveratrol reverses these effects by upregulating SIRT1 [41]. Furthermore, resveratrol treatment suppresses all indicators of inflammation including cytokine production and Th1 cell development as well as COX-2 expression and activation, thereby diminishing colitis.…”

Cancer Chemoprevention by Dietary Polyphenols

“…Till date, A substantial number of studies in cultured cells, animal models and human clinical trials have illustrated a protective role of dietary polyphenols against different types of cancers [17][18][19][20]. Polyphenols are present in fruits, vegetables, and other dietary botanicals.…”