Resveratrol protects intestinal cells from inflammation more efficiently than 5-aminosalicilic acid, a conventional drug

Resveratrol is a polyphenolic compound found in small concentrations in several dietary plants and fruits, which is able to achieve significant concentrations in the intestine after moderate intake of these foods. The presence of resveratrol in red wine enhances its relevance and accessibility. In this work, it was shown that this natural compound has a great anti-inflammatory effect on human intestinal cells, as compared to 5-aminosalicylic acid, a first-line therapeutic agent in the treatment of Inflammatory Bowel Disease. This study, focused on the molecular mechanisms underlying the anti-inflammatory action of resveratrol has revealed its ability to reduce several pro-inflammatory mediators and enzymes production and reactive oxygen species generation, at significantly lower concentrations than the conventional drug for the treatment of intestinal inflammation (5-aminosalicylic acid). Therefore, this work paves the way for the use of resveratrol as a promising nutraceutical in Inflammatory Bowel Disease context, by increasing the remission periods and limiting its progression, and subsequently delaying or preventing the development of colon carcinoma.

Authors and Affiliations:

Diana Serra ^1,2, Ana T. Rufino ^1,2, Alexandrina F. Mendes^1,2, Leonor M. Almeida ^1,2, Teresa C. P. Dinis ^1,2.

¹ CNC – Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal;

² Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal.

Abstract:

Background: Many advances have been recently made focused on the valuable help of dietary polyphenols in chronic inflammatory diseases. On the other hand, current treatment options for intestinal bowel disease patients are unsatisfying and, for this reason, it is estimated that many patients use dietary supplements to achieve extra benefits. 

Aim: The aim of this work was to analyze under a mechanistic perspective the anti-inflammatory potential of resveratrol, a natural polyphenolic compound, and to compare it with a pharmaceutical agent, 5-aminosalicylic acid, using the intestinal HT-29 cell line, as a cellular model.

Methodology and Principal Findings: In the present study, HT-29 colon epithelial cells were pre-treated with 25 μM resveratrol and/or 500 μM 5-aminosalicylic acid and then exposed to a combination of cytokines (IL-1α, TNF-α, IFN-γ) for a certain period of time. Our data showed that resveratrol, used in a concentration 20 times lower than 5‑aminosalicylic acid, was able to significantly reduce NO and PGE₂ production, iNOS and COX-2 expression and reactive oxidant species formation induced by the cytokine challenge. However, as already verified with 5-aminosalicylic acid, in spite of not exhibiting any effect on IkB-α degradation, resveratrol down-regulated JAK-STAT pathway, decreasing the levels of activated STAT1 in the nucleus. Additionally, resveratrol decreased the cytokine-stimulated activation of SAPK/JNK pathway but did not counteract the cytokine-triggered negative feedback mechanism of STAT1, through p38 MAPK.

Conclusion/Significance: Taken together, our results show that resveratrol may be considered a future nutraceutical approach, promoting remission periods, limiting the inflammatory process and preventing colorectal cancer, which is common in these patients.

Journal: PLos ONE

Link: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0109048