title: Intestinal anti-inflammatory activity of red wine extract: unveiling the mechanisms in colonic epithelial cells.
abstract: The development of new therapeutic approaches, combining efficacy and safety against intestinal inflammation, notably inflammatory bowel disease (IBD), has emerged as an important goal due to the significant side effects and the lack of effectiveness of standard current therapies. Recently, several studies described the health-promoting effects of red wine, including anti-inflammatory properties, but the molecular mechanisms underlying its beneficial role remain largely unknown. Red wine is rich in phenolic compounds and it has been suggested that the positive effect of red wine intake might be attributed not only to the antioxidant properties of these compounds but also to the modulation of signalling cascades in connection with physiological and pathophysiological conditions such as inflammatory processes. This study assesses the potential anti-inflammatory action of a red wine extract (RWE) enriched in polyphenols in a cellular model of intestinal inflammation using cytokines-stimulated HT-29 colon epithelial cells. RWE suppressed cytokines-induced IκB degradation and interleukin-8 production in a dose-dependent manner. Coherently, key inflammatory mediators downstream NF-κB activation; notably cyclooxygenase-2 and inducible nitric oxide synthase were maintained at low levels by RWE in the presence of the cytokines. Additionally, RWE inhibited both the increase of nitric oxide derived from iNOS and of protein tyrosine nitration, a biomarker of nitrosative stress that typically requires the reaction of nitric oxide with the superoxide radical. Taken together, the anti-inflammatory action of RWE, mechanistically supported by the modulation of cascades orchestrated by NF-κB and involving nitric oxide, suggests that RWE (a readily straightforward preparation when compared with the purification of specific compounds) may represent a simple and inexpensive therapeutic strategy in the context of intestinal inflammation.
authors.affiliation: Center for Neurosciences and Cell Biology and Faculty of Pharmacy, University of Coimbra, Health Sciences Campus, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal.
authors.forename: Carla
authors.initials: C
authors.lastname: Nunes
authors.forename: Elisabete
authors.initials: E
authors.lastname: Ferreira
authors.forename: Víctor
authors.initials: V
authors.lastname: Freitas
authors.forename: Leonor
authors.initials: L
authors.lastname: Almeida
authors.forename: Rui M
authors.initials: RM
authors.lastname: Barbosa
authors.forename: João
authors.initials: J
authors.lastname: Laranjinha
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D019073:HT29 Cells; D006801:Humans; D020672:I-kappa B Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy; D007371:Interferon-gamma / Q000378:metabolism; D007375:Interleukin-1 / Q000378:metabolism; D016209:Interleukin-8 / Q000037:antagonists & inhibitors / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects*; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D059808:Polyphenols / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014920:Wine / Q000032:analysis*
chemical_list: D000893:Anti-Inflammatory Agents; D020672:I-kappa B Proteins; D018836:Inflammation Mediators; D007375:Interleukin-1; D016209:Interleukin-8; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D059808:Polyphenols; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha; D009569:Nitric Oxide; D007371:Interferon-gamma; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human