Polyphenols from the Apulian grapes and wines Primitivo and Negramaro inhibit matrix metalloproteinase activity and production in human monocytoid cells

Red wine is a treasured source of polyphenols, such as stilbenes, flavonols and hydroxycinnamic acids, depending on different factors, such as grape cultivar and wine-making practices. The red wine polyphenols (RWPs) have long been associated to reduced mortality and morbidity from cardiovascular diseases and cancer. Since matrix metalloproteinase (MMP) activity is involved in extracellular matrix degradation, a crucial step both in inflammation and cell migration, aim of this study was to examine the effects of specific classes of polyphenols from Primitivo and Negroamaro grapes and wines produced in the Apulian region (Southern Italy), on the release and activity of MMP-9 in human monocytoid cells. U937 monocitoid cells were pre-treated with increasing concentrations of polyphenolic extracts (PE) of Primitivo and Negramaro grape and wine, before stimulation with 30 nM phorbol myristate acetate (PMA) for 24 h. The release and activity of MMP-9 in culture medium was tested by ELISA and zymography, respectively. Both Primitivo and Negroamaro PE exhibited a concentration-dependent inhibition of MMP-9 release and activity, without any reduction in cell viability. The inhibitory effect was higher than that produced by individual chemically synthesized polyphenols.. In this study, the PE from Primitivo and Negramaro grapes and red wines were characterized, and shown to significantly and synergistically inhibit the monocyte-derived release and activity of extracellular matrix proteases. These inhibitory effects could explain, at least in part, the anti-inflammatory and anti-cancerogenic properties of RWP.