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      Wine consumption and intestinal redox homeostasis

      review-article
      a , b , a , a , a , a , *
      Redox Biology
      Elsevier
      AKT, serine/threonine protein kinase (v-akt murine thimoma viral oncogene homolog1), apoB48, apolipoprotein B48, CD, Crohns disease, COX-2, cyclooxygenase-2, Cys, cysteine, DSS, dextran sodium sulfate, ERK, extracellular signal-regulated kinase, GRP, grape reaction product, GSH, reduced glutathione, IBD, inflammatory bowel disease, IKB, inhibitor of NF-κB, IL, interleukin, iNOS, inducible nitric oxide synthase, IFN, interferon, LPS, lipopolysaccharide, MAPK, mitogen-activated protein kinase, NADPH, nicotinamide adenine dinucleotide phosphate reduced, NF-κB, nuclear factor-κB, Nrf2, nuclear factor erythroid-2-related factor 2, PGE-2, prostaglandin E-2, ROS, reactive oxygen species, SIRT-1, silent mating type information regulation-1, TNF-α, tumor necrosis factor alpha, UC, Ulcerative Colitis, Polyphenols, Wine, Antioxidants, Gut, Inflammation, Oxidative stress

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          Abstract

          Regular consumption of moderate doses of wine is an integral part of the Mediterranean diet, which has long been considered to provide remarkable health benefits. Wine׳s beneficial effect has been attributed principally to its non-alcoholic portion, which has antioxidant properties, and contains a wide variety of phenolics, generally called polyphenols. Wine phenolics may prevent or delay the progression of intestinal diseases characterized by oxidative stress and inflammation, especially because they reach higher concentrations in the gut than in other tissues. They act as both free radical scavengers and modulators of specific inflammation-related genes involved in cellular redox signaling. In addition, the importance of wine polyphenols has recently been stressed for their ability to act as prebiotics and antimicrobial agents.

          Wine components have been proposed as an alternative natural approach to prevent or treat inflammatory bowel diseases. The difficulty remains to distinguish whether these positive properties are due only to polyphenols in wine or also to the alcohol intake, since many studies have reported ethanol to possess various beneficial effects. Our knowledge of the use of wine components in managing human intestinal inflammatory diseases is still quite limited, and further clinical studies may afford more solid evidence of their beneficial effects.

          Graphical abstract

          Influence of wine phenolic components on intestinal cell function. The scheme summarized the main activities of phenolics, which are the predominant non-alcoholic components of wine. They can interfere with the development of inflammatory intestinal diseases and colorectal cancer. Phenolics multiple properties are due to both direct antioxidant effects and indirect activation of redox-sensitive cell pathways involved in negative regulation of inflammation and immune modulation.

          Furthermore, microbiota plays a role in phenolics activity: it is essential for their metabolism, enabling them to reach highest concentrations in the gut. Diversity of phenolic composition is a reflection of interindividual variation in colonic microflora; on the other hand, phenolics act as prebiotics, increasing microflora growth.

          Ethanol matrix has an undoubted role in the impact of wine on intestinal functions. Despite the well-known deleterious consequences of high ethanol consumption, it has been proved that small concentrations of ethanol are able to act as cell signals, and influence microbiota growth together with phenolics.

          Highlights

          • Wine compounds regulate inflammation and redox signaling in intestinal cells.

          • Experimental and clinical data on wine impact on intestinal function are reviewed.

          • Among different antioxidants in wine, phenolic compounds are the most representative.

          • Microbiota has a principal role in the high availability of wine polyphenols in gut.

          • The influence of wine ethanol fraction on intestinal disease is also discussed.

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          Most cited references84

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          Regulation of inflammation and redox signaling by dietary polyphenols.

          Reactive oxygen species (ROS) play a key role in enhancing the inflammation through the activation of NF-kappaB and AP-1 transcription factors, and nuclear histone acetylation and deacetylation in various inflammatory diseases. Such undesired effects of oxidative stress have been found to be controlled by the antioxidant and/or anti-inflammatory effects of dietary polyphenols such as curcumin (diferuloylmethane, a principal component of turmeric) and resveratrol (a flavonoid found in red wine). The phenolic compounds in fruits, vegetables, tea and wine are mostly derivatives, and/or isomers of flavones, isoflavones, flavonols, catechins, tocopherols, and phenolic acids. Polyphenols modulate important cellular signaling processes such as cellular growth, differentiation and host of other cellular features. In addition, they modulate NF-kappaB activation, chromatin structure, glutathione biosynthesis, nuclear redox factor (Nrf2) activation, scavenge effect of ROS directly or via glutathione peroxidase activity and as a consequence regulate inflammatory genes in macrophages and lung epithelial cells. However, recent data suggest that dietary polyphenols can work as modifiers of signal transduction pathways to elicit their beneficial effects. The effects of polyphenols however, have been reported to be more pronounced in vitro using high concentrations which are not physiological in vivo. This commentary discusses the recent data on dietary polyphenols in the control of signaling and inflammation particularly during oxidative stress, their metabolism and bioavailability.
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            Effect of a low dose of dietary resveratrol on colon microbiota, inflammation and tissue damage in a DSS-induced colitis rat model.

            The naturally occurring polyphenol resveratrol has been acknowledged with health-beneficial properties. Most of the studies dealing with its in vivo effects assay huge doses, not representative from a dietary point of view. Our aim was to ascertain whether resveratrol can exert anti-inflammatory activity in vivo at an attainable dietary dose. Rats were fed with 1 mg of resveratrol/kg/day (a human equivalent dose) for 25 days, and in the last 5 days, 5% dextran sulfate sodium (DSS) was administered to induce colitis. Effects on colon tissue damage, gut microbiota, reactive oxygen species, inflammatory markers and nitric oxide production as well as gene expression profile with microarrays were evaluated. Resveratrol increased lactobacilli and bifidobacteria as well as diminished the increase of enterobacteria upon DSS treatment. Resveratrol significantly protected the colonic mucosa architecture, reduced body weight loss, diminished the induced anemia and reduced systemic inflammation markers, colonic mucosa prostaglandin E(2), cycloxygenase-2, prostaglandin E synthase and nitric oxide levels. In addition, the expression of 2,655 genes in distal colon mucosa related to important pathways was varied. These results reinforce the concept of resveratrol as a dietary beneficial compound in intestinal inflammation at doses possibly attainable with resveratrol-enriched nutraceuticals.
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              Intestinal redox biology and oxidative stress.

              The intestinal epithelium sits at the interface between an organism and its luminal environment, and as such is prone to oxidative damage induced by luminal oxidants. Mucosal integrity is maintained by the luminal redox status of the glutathione/glutathione disulfide (GSH/GSSG) and cysteine/cystine (Cys/CySS) couples which also support luminal nutrient absorption, mucus fluidity, and a diverse microbiota. The epithelial layer is uniquely organized for rapid self-renewal that is achieved by the well-regulated processes of crypt stem cell proliferation and crypt-to-villus cell differentiation. The GSH/GSSG and Cys/CySS redox couples, known to modulate intestinal cell transition through proliferation, differentiation or apoptosis, could govern the regenerative potential of the mucosa. These two couples, together with that of the thioredoxin/thioredoxin disulfide (Trx/TrxSS) couple are the major intracellular redox systems, and it is proposed that they each function as distinctive redox control nodes or circuitry in the control of metabolic processes and networks of enzymatic reactions. Specificity of redox signaling is accomplished in part by subcellular compartmentation of the individual redox systems within the mitochondria, nucleus, endoplasmic reticulum, and cytosol wherein each defined redox environment is suited to the specific metabolic function within that compartment. Mucosal oxidative stress would result from the disruption of these unique redox control nodes, and the subsequent alteration in redox signaling can contribute to the development of degenerative pathologies of the intestine, such as inflammation and cancer. Copyright © 2012 Elsevier Ltd. All rights reserved.
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                Author and article information

                Contributors
                Journal
                Redox Biol
                Redox Biol
                Redox Biology
                Elsevier
                2213-2317
                18 June 2014
                18 June 2014
                2014
                : 2
                : 795-802
                Affiliations
                [a ]Department of Clinical and Biological Sciences, University of Turin at San Luigi Gonzaga Hospital, Orbassano, Turin 10043, Italy
                [b ]Department of Biomedical Sciences, University of Cagliari, Cagliari 09124, Italy
                Author notes
                [* ]Corresponding author. giuseppe.poli@ 123456unito.it
                Article
                S2213-2317(14)00080-9
                10.1016/j.redox.2014.06.008
                4085343
                323b8e60-4d78-48d5-b382-785809567fbd
                © 2014 The Authors

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).

                History
                : 20 May 2014
                : 11 June 2014
                : 13 June 2014
                Categories
                Review Article

                akt, serine/threonine protein kinase (v-akt murine thimoma viral oncogene homolog1),apob48, apolipoprotein b48,cd, crohns disease,cox-2, cyclooxygenase-2,cys, cysteine,dss, dextran sodium sulfate,erk, extracellular signal-regulated kinase,grp, grape reaction product,gsh, reduced glutathione,ibd, inflammatory bowel disease,ikb, inhibitor of nf-κb,il, interleukin,inos, inducible nitric oxide synthase,ifn, interferon,lps, lipopolysaccharide,mapk, mitogen-activated protein kinase,nadph, nicotinamide adenine dinucleotide phosphate reduced,nf-κb, nuclear factor-κb,nrf2, nuclear factor erythroid-2-related factor 2,pge-2, prostaglandin e-2,ros, reactive oxygen species,sirt-1, silent mating type information regulation-1,tnf-α, tumor necrosis factor alpha,uc, ulcerative colitis,polyphenols,wine,antioxidants,gut,inflammation,oxidative stress

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