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.
OBJECTIVE
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.
Laboratory of Nutrigenomics and Vascular Biology, Institute of Clinical Physiology, National Research Council, Campus Ecotekne, Via Monteroni, 73100, Lecce, Italy.
Nadia
N
Calabriso
Laboratory of Nutrigenomics and Vascular Biology, Institute of Clinical Physiology, National Research Council, Campus Ecotekne, Via Monteroni, 73100, Lecce, Italy.
Egeria
E
Scoditti
Laboratory of Nutrigenomics and Vascular Biology, Institute of Clinical Physiology, National Research Council, Campus Ecotekne, Via Monteroni, 73100, Lecce, Italy.
Marika
M
Massaro
Laboratory of Nutrigenomics and Vascular Biology, Institute of Clinical Physiology, National Research Council, Campus Ecotekne, Via Monteroni, 73100, Lecce, Italy.|Department of Biological and Environmental Science and Technologies, University of Salento, Lecce, Italy.
Mariangela
M
Pellegrino
Department of Biological and Environmental Science and Technologies, University of Salento, Lecce, Italy.
Carlo
C
Storelli
Institute of Science of Food Production, National Research Council, Lecce, Italy.
Ilaria
I
Ingrosso
Institute of Science of Food Production, National Research Council, Lecce, Italy.
Giovanna
G
Giovinazzo
Laboratory of Nutrigenomics and Vascular Biology, Institute of Clinical Physiology, National Research Council, Campus Ecotekne, Via Monteroni, 73100, Lecce, Italy. maria.carluccio@ifc.cnr.it.
Maria Annunziata
MA
Carluccio
D000893:Anti-Inflammatory Agents / Q000032:analysis / Q000494:pharmacology*; D050197:Atherosclerosis / Q000188:drug therapy; D002448:Cell Adhesion / Q000187:drug effects; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D003373:Coumaric Acids / Q000032:analysis / Q000494:pharmacology*; D019040:E-Selectin / Q000235:genetics / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects; D044948:Flavonols / Q000032:analysis / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D007558:Italy; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D059808:Polyphenols / Q000032:analysis / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013267:Stilbenes / Q000032:analysis / Q000494:pharmacology*; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D014920:Wine / Q000032:analysis*
D000893:Anti-Inflammatory Agents; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D003373:Coumaric Acids; D019040:E-Selectin; D044948:Flavonols; D016328:NF-kappa B; D059808:Polyphenols; D012333:RNA, Messenger; C546936:SELE protein, human; D013267:Stilbenes; D018808:Transcription Factor AP-1; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1
E-Selectin; Intercellular adhesion molecule-1; Macrophage colony-stimulating factor; Monocyte chemoattractant protein-1; Vascular cell adhesion molecule-1