Grape pomace extract attenuates overwhelming inflammatory response in intestinal epithelial and endothelial cells:

Inflammatory bowel diseases (IBD) are chronic inflammatory conditions of the gastrointestinal tract, also associated with systemic vascular manifestations. In IBD, the incidence of cardiovascular disease appears related to an increase of oxidative stress and endothelial dysfunction. Grape pomace contains high levels of anti-oxidant polyphenols, which are able to counteract chronic inflammatory disease. The aim of this study was to determine whether grape pomace polyphenolic extract (GPE) was able to mitigate the overwhelming inflammatory response in enterocyte-like cells and to improve vascular function. The intestinal epithelial Caco-2 cells, grown in monolayers or in co-culture with endothelial cells (Caco-2/HMEC-1), were treated with different concentra-tions of GPE (1, 5, 10 µg GAEs/mL) for 2h and then stimulated with lipopolysaccharide(LPS) and tumor necrosis factor(TNF)-? for 16h. Through multiple assays, the expression of intestinal and endothelial inflammatory mediators, intracellular ROS levels, NF-?B activity as well as the en-dothelial-leukocyte adhesion were analyzed. The results showed that GPE supplementation prevented, in a concentration-dependent manner, the expression and release of interleukin(IL)-6, monocyte chemoattractant protein(MCP)-1 and matrix metalloproteinases(MMP)-9 and MMP-2 in Caco-2 cells. GPE also suppressed the intestinal gene expression of several pro-inflammatory mediators, such as IL-1?, TNF-?, macrophage colony-stimulating factor(M-CSF), C-X-C motif ligand(CXCL)-10, intercellular adhesion molecule(ICAM)-1, vascular cell adhesion mole-cule(VCAM)-1 and cyclooxygenase(COX)-2. The GPE anti-inflammatory effect was related to the inhibition of NF-?B activity and intracellular ROS levels. Furthermore, transepithelial GPE in-hibited the endothelial expression of IL-6, MCP-1, VCAM-1 and ICAM-1 and the subsequent ad-hesion of leukocyte to the endothelial cells under pro-inflammatory conditions. In conclusion, our findings suggest grape pomace as a natural source of polyphenols, with multiple healthy pro-moting properties, which could contribute to mitigate gut chronic inflammatory diseases and improve vascular endothelial function.