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Background: Inflammatory cytokines and matrix metalloproteinases (MMPs) produced by resident and inflammatory cells in response to periodontopathogens play a major role in the tissue destruction observed in periodontitis, which is a disease that affects tooth-supporting structures. In the present study, we investigate the effects of licorice-derived licoricidin (LC) and licorisoflavan A (LIA) on the secretion of various cytokines and MMPs by human monocyte-derived macrophages stimulated with Aggregatibacter actinomycetemcomitans (previously Actinobacillus actinomycetemcomitans) lipopolysaccharide (LPS)., Methods: Macrophages were treated with non-toxic concentrations of LC or LIA before being stimulated with A. actinomycetemcomitans LPS. The secretion of cytokines and MMPs and the activation of nuclear factor-kappa B (NF-κB) p65 and activator protein (AP)-1 were assessed by enzyme-linked immunosorbent assays., Results: LC and LIA inhibited the secretion of interleukin (IL)-6 and chemokine (C-C motif) ligand 5 in a concentration-dependent manner but did not affect the secretion of IL-8 by LPS-stimulated macrophages. LC and LIA also inhibited the secretion of MMP-7, -8, and -9 by macrophages. The suppression of cytokine and MMP secretion by LC and LIA was associated with the reduced activation of NF-κB p65 but not that of AP-1., Conclusion: The present study suggests that LC and LIA have potential for the development of novel host-modulating strategies for the treatment of cytokine and/or MMP-mediated disorders such as periodontitis.

Plant extracts and/or secondary metabolites are receiving considerable attention as therapeutic agents for treating inflammatory diseases such as periodontitis, which affects the tooth supporting tissues. The aim of this study was to investigate the effect of a Grindelia robusta extract enriched in saponins and polyphenols on Aggregatibacter actinomycetemcomitans lipopolysaccharide (LPS)-induced inflammatory mediator (IL-6, TNF-a, RANTES, MCP-1, PGE(2) ) and matrix metalloproteinase (MMP-1, -3, -7, -8, -9, -13) secretion by macrophages. LPS induced a marked increase in the secretion of all inflammatory mediators and MMPs tested by macrophages, as determined by enzyme-linked immunosorbent assays. At non-cytotoxic concentrations, the G. robusta extract inhibited dose-dependently the secretion of IL-6, RANTES, MCP-1 and, to a lesser extent, PGE(2) and TNF-a. Such inhibition was also observed for MMP-1, -3, -7, -8, -9 and -13 secretion. This ability of G. robusta extract to reduce the LPS-induced secretion of inflammatory mediators and MMPs was associated with a reduction of nuclear factor-kappa B (NF-kB) p65 activation. The results suggest that G. robusta extract possesses an antiinflammatory therapeutic potential through its capacity to reduce the accumulation of inflammatory mediators and MMPs., (Copyright © 2010 John Wiley & Sons, Ltd.)

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-kappaB) 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-kappaB p65 and AP-1 activation. Also, GSE dose-dependently inhibited the activity of MMP-1 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.

Recent studies brought evidence regarding the potential beneficial effects of cranberry polyphenols for periodontal infections. In this study, we evaluated the capacity of a proanthocyanidin-rich cranberry fraction to protect macrophages and oral epithelial cells against cytotoxicity induced by bacterial components. U937 cells, differentiated into adherent macrophage-like cells, as well as oral epithelial cells were treated with cell wall or lipopolysaccharide preparations from periodontopathogens. Cell viability was monitored using a commercial MTT (3-[4,5-diethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay. The cytoprotective effect was evaluated by pre-incubating human cells with a proanthocyanidin-rich cranberry fraction prior to treatment with the bacterial components at toxic concentrations. Among the various bacterial components tested, Peptostreptotoccus micros cell wall was found to be the most toxic for macrophages and epithelial cells and was thus selected for further analyses. Treatment of monocyte-derived macrophages with cell wall of P. micros (20 microg/ml) decreased the cell viability by approximately 50%. Adding the cranberry fraction prior to treating cells with P. micros cell wall dose-dependently protected monocyte-derived macrophages from the toxic effect. A dose-dependent cytoprotective effect of the cranberry fraction was also observed with oral epithelial cells treated with P. micros cell wall. This study suggests that cranberry polyphenols may exert a protective effect for host cells against the toxicity induced by bacterial components., ((c) 2009 John Wiley & Sons, Ltd.)

Periodontitis is a chronic inflammatory disease of bacterial etiology that affects tooth-supporting tissues. The aim of the present study was to investigate the effect of Rhamnus alpinus extracts on lipopolysaccharide (LPS)-induced chemokine secretion by human macrophage-like cells. Phorbol myristic acid-differentiated macrophages were stimulated with Aggregatibacter actinomycetemcomitans LPS in the absence and presence of various concentrations of the extracts. The secretion of interleukin-8 (IL-8), regulated on activation normal T cell expressed and secreted (RANTES), and monocyte chemotactic protein (MCP)-1 was measured using enzyme-linked immunosorbent assays (ELISA). Activation of NF-kappaB p65 was evaluated with an ELISA-based kit containing immobilized oligonucleotides with an NF-kappaB consensus binding site. A. actinomycetemcomitans LPS (1 microg/ml) induced a marked increase in the secretion of IL-8 and RANTES by monocyte-derived macrophages. At non-cytotoxic concentrations, the R. alpinus leaf extract, which contains polyphenols, inhibited the secretion of RANTES and, to a lesser extent, IL-8 in a dose-dependent manner. The extract also decreased the basal levels of MCP-1 secreted by monocyte-derived macrophages. The extract appeared to exert its anti-inflammatory effect by inhibiting NF-kappaB p65 activation. Our results suggest that the leaf extract of R. alpinus possesses a therapeutic potential through its capacity to limit the infiltration of immune cells into periodontal sites. This may impede the progression and aggravation of inflammation given that the migration of immune cells plays an important role in the outcome of periodontitis.

Background: Periodontal diseases are a group of inflammatory disorders initiated by specific Gram-negative periodontopathogenic bacteria that lead to the destruction of tooth-supporting tissues. In this study, we tested whether a carbon dioxide-supercritical extract of Glycyrrhiza uralensis (licorice) can reduce the periodontopathogen-induced inflammatory response., Methods: Monocyte-derived macrophages were treated with various concentrations of the licorice extract prior to being stimulated with Aggregatibacter actinomycetemcomitans (previously Actinobacillus actinomycetemcomitans) and Porphyromonas gingivalis lipopolysaccharide (LPS). The capacity of the licorice extract to mediate the inflammatory response was also tested in an ex vivo whole blood model stimulated with P. gingivalis LPS. The secretion of interleukin (IL)-1beta, -6, and -8 and tumor necrosis factor-alpha (TNF-alpha) in both models was assessed by enzyme-linked immunosorbent assays. Changes in the phosphorylation state of macrophage intracellular kinases induced by A. actinomycetemcomitans LPS and the licorice extract in the macrophage model were characterized by immunoblotting., Results: The licorice extract exhibited potent anti-inflammatory properties, inhibiting the periodontopathogen LPS-induced IL-1beta, -6, and -8 and TNF-alpha responses of macrophages. The licorice extract inhibited the phosphorylation of important macrophage intracellular signaling proteins, including nuclear factor-kappa B p65 nuclear transcription factor and Jun proto-oncogene-encoded activator protein (AP) 1 transcription factor, which are involved in inflammatory signaling pathways. The licorice extract was also a potent inhibitor of the proinflammatory cytokine response in the ex vivo human whole blood model., Conclusion: This CO(2)-supercritical licorice extract is a potential candidate for the development of a new therapy to prevent and/or treat periodontitis-associated tissue destruction.