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Intestinal anti-inflammatory activity of red wine extract: unveiling the mechanisms in colonic epithelial cells
Carla Nunes1, Elisabete Ferreira, Víctor Freitas
1Center for Neurosciences and Cell Biology and Faculty of Pharmacy, University of Coimbra, Health Sciences Campus, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal.
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.
Insights
Red wine extract (RWE) shows anti-inflammatory effects in intestinal inflammation models. RWE modulates key inflammatory pathways like NF-κB, suggesting a potential therapeutic strategy for inflammatory bowel disease (IBD).
Area of Science:
- Gastroenterology and Molecular Biology
- Natural Product Therapeutics
Background:
- Current therapies for inflammatory bowel disease (IBD) have limitations in efficacy and safety.
- Red wine consumption is associated with health benefits, including anti-inflammatory properties, but mechanisms are unclear.
- Phenolic compounds in red wine are hypothesized to exert effects via antioxidant activity and signaling pathway modulation.
Purpose of the Study:
- To investigate the anti-inflammatory potential of a polyphenol-rich red wine extract (RWE).
- To elucidate the molecular mechanisms of RWE's action in a cellular model of intestinal inflammation.
Main Methods:
- Utilized a cellular model of intestinal inflammation using cytokine-stimulated HT-29 colon epithelial cells.
- Assessed the effects of RWE on key inflammatory markers, including IκB degradation, interleukin-8 production, cyclooxygenase-2, and inducible nitric oxide synthase (iNOS).
- Measured nitric oxide production and protein tyrosine nitration to evaluate nitrosative stress.
Main Results:
- RWE significantly suppressed cytokine-induced IκB degradation and interleukin-8 production in a dose-dependent manner.
- RWE maintained low levels of cyclooxygenase-2 and iNOS in the presence of inflammatory cytokines.
- RWE inhibited nitric oxide generation from iNOS and reduced protein tyrosine nitration, indicating mitigation of nitrosative stress.
Conclusions:
- Red wine extract exhibits significant anti-inflammatory actions in a cellular model of intestinal inflammation.
- The anti-inflammatory effects are mechanistically linked to the modulation of NF-κB signaling pathways and nitric oxide production.
- RWE presents a potentially simple, inexpensive, and effective therapeutic strategy for managing intestinal inflammation.
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