Resveratrol Suppresses Colitis and Colon Cancer Associated with Colitis

Abstract

Resveratrol is a naturally occurring polyphenol that exhibits pleiotropic health beneficial effects, including anti-inflammatory, cardio-protective, and cancer-protective activities. It is recognized as one of the more promising natural molecules in the prevention and treatment of chronic inflammatory and autoimmune disorders. Ulcerative colitis is an idiopathic, chronic inflammatory disease of the colon associated with a high colon cancer risk. Here, we used a dextran sulfate sodium (DSS) mouse model of colitis, which resembles human ulcerative colitis pathology. Resveratrol mixed in food ameliorates DSS-induced colitis in mice in a dose-dependent manner. Resveratrol significantly improves inflammation score, downregulates the percentage of neutrophils in the mesenteric lymph nodes and lamina propria, and modulates CD3 + T cells that express tumor necrosis factor-α and IFN-γ. Markers of inflammation and inflammatory stress (p53 and p53-phospho-Ser 15) are also downregulated by resveratrol. Because chronic colitis drives colon cancer risk, we carried out experiments to determine the chemopreventive properties of resveratrol. Tumor incidence is reduced from 80% in mice treated with azoxymethane (AOM) + DSS to 20% in mice treated with AOM + DSS + resveratrol (300 ppm). Tumor multiplicity also decreased with resveratrol treatment. AOM + DSS-treated mice had 2.4 ± 0.7 tumors per animal compared with AOM + DSS + 300 ppm resveratrol, which had 0.2 ± 0.13 tumors per animal. The current study indicates that resveratrol is a useful, nontoxic complementary and alternative strategy to abate colitis and potentially colon cancer associated with colitis. Cancer Prev Res; 3(4); 549-59. ©2010 AACR.

Reduction in oxidative stress levels in the colonic mucosa without fecal stream after the application of enemas containing aqueous Ilex paraguariensis extract

“…In plants, they protect against insects and microorganisms and are responsible for pigmentation and some organoleptic characteristics of food 8 . Recently, natural polyphenolic substances such as curcumin (extract from Curcuma longa) and revesterol (extract from grapes) are being increasingly used as antioxidant substances in different experimental models of colitis 9,10,11,12 . Although it has been demonstrated experimentally that the pathogenesis of diversion colitis (DC) is related to oxidative stress due to changes in the supply of short-chain fatty acids (SCFA) to the excluded colon, to the best of our knowledge, the antioxidant effects of natural polyphenols in the aqueous extract and fed a standard rodent chow diet.…”

Chemically-Induced DNA Damage, Mutagenesis, and Cancer

“…The pathophysiological and histopathological features/ manifestations of colon cancer include aberrant crypt foci (ACF), hyperplasia, adenocarcinoma, and adenoma [258]. In models induced with AOM or AOM plus DSS, the oral administration (in the gavage or diet) of resveratrol decreased the incidence [259,260] [261], and Nrf2 [261], and reduced the expression of COX-2 [259,261], inducible nitric oxide synthase (iNOS) [259,261], TNF-α [259], aldose reductase [261], NF-κB [261], and p-protein kinase C-β2 (PKC-β2) [261]. It has been propounded that resveratrol down-regulates the aldose reductase-dependent activation of NF-κB and PKC-β2, with an ensuing lowering of the expression levels of COX-2 and iNOS [261].…”

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.…”