Grape Seed Extract Suppresses Lipopolysaccharide-Induced Matrix Metalloproteinase (MMP) Secretion by Macrophages and Inhibits Human MMP-1 and-9 Activities

Background: Matrix metalloproteinases (MMPs) produced by resident and inflammatory cells in response to Gram-negative periodontopathogens play a major role in the tissue destruction observed during periodontitis, a disease that affects tooth - supporting structures. In this study, we investigated the effect of grape seed extract (GSE) on MMP secretion by human monocyte-derived macrophages stimulated with Aggregatibacter actinomycetemcomitans (previously Actinobacillus actinomycetemcomitans) lipopolysaccharide (LPS) and on the activity of human recombinant MMP-1 and -9. Methods: Macrophages were treated with various concentrations of GSE prior to being stimulated with A. actinomycetemcomitans LPS. The secretion of MMPs and activation of nuclear factor-kappa B (NF-kappa B) p65 and activator protein-1 (AP-1) were assessed by enzyme-linked immunosorbent assay (ELISA). The effect of GSE on the catalytic activity of human recombinant MMP-1 and -9 was tested using fluorogenic assays. Results: GSE inhibited the secretion of MMP-1, -3, -7, -8, -9, and -13 by LPS-stimulated macrophages in a concentration-dependent manner. The suppression of MMP secretion was associated with inhibition of NF-kappa B p65 and AP-1 activation. Also, GSE dose-dependently inhibited the activity of MMPA and -9. Conclusion: The present study suggests that GSE may be potentially used in the development of novel host-modulating strategies for the treatment of MMP-mediated disorders such as periodontitis. J Periodontol 2009;80:1875-1882.