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J Nutr Biochem. 2016 Oct;36:21-30. doi: 10.1016/j.jnutbio.2016.07.007. Epub 2016 Aug 4.

Resveratrol improves TNF-α-induced endothelial dysfunction in a coculture model of a Caco-2 with an endothelial cell line.

Author information

1
Department of Food Science and Technology, Federal University of Santa Catarina, Admar Gonzaga 1346, 88034001 Florianópolis, Brazil; Department of Food Safety and Food Quality, Ghent University, Coupure Links 653, 9000 Gent, Belgium.
2
Department of Food Safety and Food Quality, Ghent University, Coupure Links 653, 9000 Gent, Belgium.
3
Department of Food Safety and Food Quality, Ghent University, Coupure Links 653, 9000 Gent, Belgium; Department of Food Engineering, Faculty of Chemical and Metallurgical Engineering, Istanbul Technical University, 34469 Maslak, Istanbul, Turkey.
4
Department of Food Science and Technology, Federal University of Santa Catarina, Admar Gonzaga 1346, 88034001 Florianópolis, Brazil.
5
Department of Crop Protection, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, 9000 Gent, Belgium.
6
Department of Industrial Biological Sciences, Faculty of Bioscience Engineering, Ghent University, Graaf Karel de Goedelaan 5, 8500 Kortrijk, Belgium.
7
Department of Food Engineering, Faculty of Chemical and Metallurgical Engineering, Istanbul Technical University, 34469 Maslak, Istanbul, Turkey.
8
Department of Food Safety and Food Quality, Ghent University, Coupure Links 653, 9000 Gent, Belgium. Electronic address: charlotte.grootaert@ugent.be.

Abstract

The bioactivity of trans-resveratrol (RSV), an important wine polyphenol, and of its metabolites was investigated in a more relevant setup comprising an in vitro coculture cell model that combines intestinal absorption and conjugation with changes in endothelial function, which is primarily affected in cardiovascular diseases. Caco-2 and endothelial EA.hy926 cells were grown in a coculture, and Caco-2 cells were treated with RSV in the coculture and in two different sequential setups for 4 h and 24 h. Transported metabolites were investigated by UPLC-MS/MSE, and the effects on NO production, ROS inhibition and secretion of vascular endothelial growth factor (VEGF), interleukin-8 (IL-8) and intercellular adhesion molecule-1 (ICAM-1) were evaluated in TNF-α-activated and nonactivated endothelial cells. RSV and four conjugated metabolites, two sulfates and two glucuronides, were identified after intestinal transport. In both coculture and sequential systems, RSV at 20 μM strongly induced NO production. Changes in ROS and NO levels demonstrated a clear effect of crosstalk between cells in the coculture. The secretion of proinflammatory cytokines and VEGF was largely increased by treatment with TNF-α (inflammatory condition). The polyphenol intervention significantly reduced the levels of VEGF, ROS, IL-8 and ICAM-1, with a more pronounced effect in TNF-α-activated endothelial cells. In conclusion, RSV and its metabolites showed accentuated bioactivity on TNF-α-induced inflammation, and the metabolism of endothelial cells as a biological target was not only influenced by these phenolics but also by the communication between distinct cell lines, showing a new perspective for investigations on polyphenol intervention and its biological outcomes.

KEYWORDS:

Cardiovascular disease; Coculture; ICAM-1; Intestine; Nitric oxide; Resveratrol

PMID:
27560195
DOI:
10.1016/j.jnutbio.2016.07.007
[Indexed for MEDLINE]

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