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

• Published in: Molecules (Basel, Switzerland) Switzerland), 2016-08, Vol.21 (9), p.1147
• Main Authors: Calabriso, Nadia, Massaro, Marika, Scoditti, Egeria, Pellegrino, Mariangela, Ingrosso, Ilaria, Giovinazzo, Giovanna, Carluccio, Maria Annunziata
• Format: Article
• Language: English
• Subjects: antioxidants; endothelium; flavonols; Fruit - chemistry; gelatinases; gene expression; Gene Expression Regulation, Enzymologic - drug effects; grape skin polyphenolic extracts; Human Umbilical Vein Endothelial Cells - enzymology; Human Umbilical Vein Endothelial Cells - pathology; Humans; inflammation; Matrix Metalloproteinase 2 - biosynthesis; Matrix Metalloproteinase 9 - biosynthesis; Models, Biological; monocytes; phenolic acids; Polyphenols - chemistry; Polyphenols - isolation & purification; Polyphenols - pharmacology; stilbenes; Vascular Remodeling - drug effects; Vasculitis - drug therapy; Vasculitis - enzymology; Vasculitis - pathology; Vitis - chemistry
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules21091147

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.