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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

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Abstract

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.

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Acknowledgments

We are grateful to the Division of Obstetrics and Gynecology at the “Vito Fazzi” Hospital in Lecce (Italy) and at the “Ignazio Veris Delli Ponti” Hospital in Scorrano (Lecce, Italy) for providing umbilical cords. We thank Sig. L. D’Amico, C. Gerardi and V. Falco (CNR—Institute of Science of Food Production, Lecce, Italy) for technical assistance with HPLC analyses and qPCR experiments; E. De Lorenzis (Biotecgen, Lecce, Italy) for nucleic acid quantification. This work was partially supported by Grants from Apulia Region (Italy), POR Strategic Projects [Grant Numbers CIP PS_101 and CIP PS_008, INNOWINE Project] and by Grants from National Operational Programme for Research and Competitiveness 2007–2013 [Grant Number PON01_01958, PIVOLIO project].

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Laboratory of Nutrigenomics and Vascular Biology, Institute of Clinical Physiology, National Research Council, Campus Ecotekne, Via Monteroni, 73100, Lecce, Italy

    Nadia Calabriso, Egeria Scoditti, Marika Massaro, Mariangela Pellegrino & Maria Annunziata Carluccio

  2. Department of Biological and Environmental Science and Technologies, University of Salento, Lecce, Italy

    Mariangela Pellegrino & Carlo Storelli

  3. Institute of Science of Food Production, National Research Council, Lecce, Italy

    Ilaria Ingrosso & Giovanna Giovinazzo

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  1. Nadia Calabriso
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  2. Egeria Scoditti
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  8. Maria Annunziata Carluccio
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Correspondence to Maria Annunziata Carluccio.

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Calabriso, N., Scoditti, E., Massaro, M. et al. 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. Eur J Nutr 55, 477–489 (2016). https://doi.org/10.1007/s00394-015-0865-6

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