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Molecules 2016, 21(9), 1147; doi:10.3390/molecules21091147

Red Grape Skin Polyphenols Blunt Matrix Metalloproteinase-2 and -9 Activity and Expression in Cell Models of Vascular Inflammation: Protective Role in Degenerative and Inflammatory Diseases

1
National Research Council–Institute of Clinical Physiology (CNR-IFC), Laboratory of Nutrigenomic and Vascular Biology, Lecce 73100, Italy
2
Department of Biological and Environmental Science and Technologies (DISTEBA), University of Salento, Lecce 73100, Italy
3
National Research Council–Institute of Science of Food Production, Lecce 73100, Italy
*
Author to whom correspondence should be addressed.
Academic Editors: Pedro Mena and Rafael Llorach
Received: 30 June 2016 / Revised: 17 August 2016 / Accepted: 25 August 2016 / Published: 29 August 2016
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Abstract

Matrix metalloproteinases (MMPs) are endopeptidases responsible for the hydrolysis of various components of extracellular matrix. MMPs, namely gelatinases MMP-2 and MMP-9, contribute to the progression of chronic and degenerative diseases. Since gelatinases’ activity and expression are regulated by oxidative stress, we sought to evaluate whether supplementation with polyphenol-rich red grape skin extracts modulated the matrix-degrading capacity in cell models of vascular inflammation. Human endothelial and monocytic cells were incubated with increasing concentrations (0.5–25 μg/mL) of Negroamaro and Primitivo red grape skin polyphenolic extracts (NSPE and PSPE, respectively) or their specific components (0.5–25 μmol/L), before stimulation with inflammatory challenge. NSPE and PSPE inhibited, in a concentration-dependent manner, endothelial invasion as well as the MMP-9 and MMP-2 release in stimulated endothelial cells, and MMP-9 production in inflamed monocytes, without affecting tissue inhibitor of metalloproteinases (TIMP)-1 and TIMP-2. The matrix degrading inhibitory capacity was the same for both NSPE and PSPE, despite their different polyphenolic profiles. Among the main polyphenols of grape skin extracts, trans-resveratrol, trans-piceid, kaempferol and quercetin exhibited the most significant inhibitory effects on matrix-degrading enzyme activities. Our findings appreciate the grape skins as rich source of polyphenols able to prevent the dysregulation of vascular remodelling affecting degenerative and inflammatory diseases. View Full-Text
Keywords: antioxidants; gelatinases; endothelium; monocytes; grape skin polyphenolic extracts; gene expression; inflammation; stilbenes; flavonols; phenolic acids antioxidants; gelatinases; endothelium; monocytes; grape skin polyphenolic extracts; gene expression; inflammation; stilbenes; flavonols; phenolic acids
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Calabriso, N.; Massaro, M.; Scoditti, E.; Pellegrino, M.; Ingrosso, I.; Giovinazzo, G.; Carluccio, M.A. Red Grape Skin Polyphenols Blunt Matrix Metalloproteinase-2 and -9 Activity and Expression in Cell Models of Vascular Inflammation: Protective Role in Degenerative and Inflammatory Diseases. Molecules 2016, 21, 1147.

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