Multiple anti-inflammatory and anti-atherosclerotic properties of red wine polyphenolic extracts: differential role of hydroxycinnamic acids, flavonols and stilbenes on endothelial inflammatory gene expression

• Published in: European journal of nutrition Vol. 55; no. 2; pp. 477 - 489
• Main Authors: Calabriso, Nadia, Scoditti, Egeria, Massaro, Marika, Pellegrino, Mariangela, Storelli, Carlo, Ingrosso, Ilaria, Giovinazzo, Giovanna, Carluccio, Maria Annunziata
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.03.2016; Springer Nature B.V
• Subjects: Anti-Inflammatory Agents - analysis; Anti-Inflammatory Agents - pharmacology; Atherosclerosis - drug therapy; Cell Adhesion - drug effects; Chemistry; Chemistry and Materials Science; Chemokine CCL2 - genetics; Chemokine CCL2 - metabolism; Coumaric Acids - analysis; Coumaric Acids - pharmacology; E-Selectin - genetics; E-Selectin - metabolism; Endothelial Cells - drug effects; Flavonols - analysis; Flavonols - pharmacology; Humans; Inflammation - drug therapy; Intercellular Adhesion Molecule-1 - genetics; Intercellular Adhesion Molecule-1 - metabolism; Italy; NF-kappa B - genetics; NF-kappa B - metabolism; Nutrition; Original Contribution; Oxidative Stress - drug effects; Polyphenols - analysis; Polyphenols - pharmacology; RNA, Messenger - genetics; RNA, Messenger - metabolism; Stilbenes - analysis; Stilbenes - pharmacology; Transcription Factor AP-1 - genetics; Transcription Factor AP-1 - metabolism; Vascular Cell Adhesion Molecule-1 - genetics; Vascular Cell Adhesion Molecule-1 - metabolism; Wine - analysis; Monocyte chemoattractant protein-1; E-Selectin; Macrophage colony-stimulating factor; Vascular cell adhesion molecule-1; Intercellular adhesion molecule-1
• ISSN: 1436-6207; 1436-6215
• DOI: 10.1007/s00394-015-0865-6

Purpose The aim of the study was to evaluate the vascular anti-inflammatory effects of polyphenolic extracts from two typical South Italy red wines, the specific contribution of individual polyphenols and the underlying mechanisms of action. Methods Human endothelial cells were incubated with increasing concentrations (1–50 μg/mL) of Primitivo and Negroamaro polyphenolic extracts (PWPE and NWPE, respectively) or pure polyphenols (1–25 μmol/L), including hydroxycinnamic acids ( p -coumaric, caffeic and caftaric acids), flavonols (kaempferol, quercetin, myricetin) or stilbenes ( trans -resveratrol, trans -piceid) before stimulation with lipopolysaccharide. Through multiple assays, we analyzed the endothelial–monocyte adhesion, the endothelial expression of adhesion molecules (ICAM-1, VCAM-1 and E-Selectin), monocyte chemoattractant protein-1 (MCP-1) and macrophage colony-stimulating factor (M-CSF), as well as ROS intracellular levels and the activation of NF-κB and AP-1. Results Both PWPE and NWPE, already at 1 μg/mL, inhibited monocyte adhesion to stimulated endothelial cells, a key event in triggering vascular inflammation. They down-regulated the expression of adhesion molecules, ICAM-1, VCAM-1, E-Selectin, as well as MCP-1 and M-CSF, at mRNA and protein levels. All polyphenols reduced intracellular ROS, and everything, except caftaric acid, inhibited the endothelial expression of adhesion molecules and MCP-1, although with different potency. Flavonols and resveratrol significantly reduced also the endothelial expression and release of M-CSF. The decrease in endothelial inflammatory gene expression was related to the inhibition of NF-κB and AP-1 activation but not to intracellular oxidative stress. Conclusions This study showed multiple anti-inflammatory and anti-atherosclerotic properties of red wine polyphenolic extracts and indentified specific bioactive polyphenols which could counteract inflammatory diseases including atherosclerosis.