PMID- 25724173 OWN - NLM STAT- MEDLINE DCOM- 20161215 LR - 20181113 IS - 1436-6215 (Electronic) IS - 1436-6207 (Linking) VI - 55 IP - 2 DP - 2016 Mar TI - 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. PG - 477-489 LID - 10.1007/s00394-015-0865-6 [doi] AB - 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 mug/mL) of Primitivo and Negroamaro polyphenolic extracts (PWPE and NWPE, respectively) or pure polyphenols (1-25 mumol/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-kappaB and AP-1. RESULTS: Both PWPE and NWPE, already at 1 mug/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-kappaB 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. FAU - Calabriso, Nadia AU - Calabriso N AD - Laboratory of Nutrigenomics and Vascular Biology, Institute of Clinical Physiology, National Research Council, Campus Ecotekne, Via Monteroni, 73100, Lecce, Italy. FAU - Scoditti, Egeria AU - Scoditti E AD - Laboratory of Nutrigenomics and Vascular Biology, Institute of Clinical Physiology, National Research Council, Campus Ecotekne, Via Monteroni, 73100, Lecce, Italy. FAU - Massaro, Marika AU - Massaro M AD - Laboratory of Nutrigenomics and Vascular Biology, Institute of Clinical Physiology, National Research Council, Campus Ecotekne, Via Monteroni, 73100, Lecce, Italy. FAU - Pellegrino, Mariangela AU - Pellegrino M AD - Laboratory of Nutrigenomics and Vascular Biology, Institute of Clinical Physiology, National Research Council, Campus Ecotekne, Via Monteroni, 73100, Lecce, Italy. AD - Department of Biological and Environmental Science and Technologies, University of Salento, Lecce, Italy. FAU - Storelli, Carlo AU - Storelli C AD - Department of Biological and Environmental Science and Technologies, University of Salento, Lecce, Italy. FAU - Ingrosso, Ilaria AU - Ingrosso I AD - Institute of Science of Food Production, National Research Council, Lecce, Italy. FAU - Giovinazzo, Giovanna AU - Giovinazzo G AD - Institute of Science of Food Production, National Research Council, Lecce, Italy. FAU - Carluccio, Maria Annunziata AU - Carluccio MA AD - 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. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150228 PL - Germany TA - Eur J Nutr JT - European journal of nutrition JID - 100888704 RN - 0 (Anti-Inflammatory Agents) RN - 0 (CCL2 protein, human) RN - 0 (Chemokine CCL2) RN - 0 (Coumaric Acids) RN - 0 (E-Selectin) RN - 0 (Flavonols) RN - 0 (NF-kappa B) RN - 0 (Polyphenols) RN - 0 (RNA, Messenger) RN - 0 (SELE protein, human) RN - 0 (Stilbenes) RN - 0 (Transcription Factor AP-1) RN - 0 (Vascular Cell Adhesion Molecule-1) RN - 126547-89-5 (Intercellular Adhesion Molecule-1) SB - IM MH - Anti-Inflammatory Agents/analysis/*pharmacology MH - Atherosclerosis/drug therapy MH - Cell Adhesion/drug effects MH - Chemokine CCL2/genetics/metabolism MH - Coumaric Acids/analysis/*pharmacology MH - E-Selectin/genetics/metabolism MH - Endothelial Cells/drug effects MH - Flavonols/analysis/*pharmacology MH - Humans MH - Inflammation/drug therapy MH - Intercellular Adhesion Molecule-1/genetics/metabolism MH - Italy MH - NF-kappa B/genetics/metabolism MH - Oxidative Stress/drug effects MH - Polyphenols/analysis/*pharmacology MH - RNA, Messenger/genetics/metabolism MH - Stilbenes/analysis/*pharmacology MH - Transcription Factor AP-1/genetics/metabolism MH - Vascular Cell Adhesion Molecule-1/genetics/metabolism MH - Wine/*analysis OTO - NOTNLM OT - E-Selectin OT - Intercellular adhesion molecule-1 OT - Macrophage colony-stimulating factor OT - Monocyte chemoattractant protein-1 OT - Vascular cell adhesion molecule-1 EDAT- 2015/03/01 06:00 MHDA- 2016/12/16 06:00 CRDT- 2015/03/01 06:00 PHST- 2014/11/06 00:00 [received] PHST- 2015/02/18 00:00 [accepted] PHST- 2015/03/01 06:00 [entrez] PHST- 2015/03/01 06:00 [pubmed] PHST- 2016/12/16 06:00 [medline] AID - 10.1007/s00394-015-0865-6 [pii] AID - 10.1007/s00394-015-0865-6 [doi] PST - ppublish SO - Eur J Nutr. 2016 Mar;55(2):477-489. doi: 10.1007/s00394-015-0865-6. Epub 2015 Feb 28.