Periodontitis is a chronic inflammatory disease that affects the tooth supporting tissues. Gingival fibroblasts are the most abundant cells in periodontal tissues and participate actively in the host inflammatory response to periodontopathogens, which is known to mediate local tissue destruction in periodontitis. The aim of this study was to investigate the effect of a proanthocyanidin-enriched cranberry fraction, prepared from cranberry juice concentrate, on inflammatory mediator production by gingival fibroblasts stimulated by the lipopolysaccharide (LPS) of Aggregatibacter actinomycetemcomitans. Interleukin (IL)-6, IL-8, and prostaglandin E(2) (PGE(2)) production by fibroblasts treated with the cranberry fraction and stimulated by A. actinomycetemcomitans LPS was evaluated by enzyme-linked immunosorbent assay. Changes induced by A. actinomycetemcomitans LPS and the cranberry fraction in the expression and phosphorylation state of fibroblast intracellular signaling proteins were characterized by antibody microarrays. The LPS-induced IL-6, IL-8, and PGE(2) responses of gingival fibroblasts were inhibited by treatment with the cranberry fraction. This fraction was found to inhibit fibroblast intracellular signaling proteins, a phenomenon that may lead to a down-regulation of activating protein-1 activity. Cranberry components also reduced cyclooxygenase 2 expression. This study suggests that cranberry juice contains molecules with interesting properties for the development of new host-modulating therapeutic strategies in the adjunctive treatment of periodontitis.

We investigated the antimicrobial effect of constituents of the American cranberry (Vaccinium macrocarpon); sugar plus organic acids, phenolics, and anthocyanins, against Escherichia coli O157:H7. Each fractional component was assayed over a 24-h period with 5-log initial inocula to determine the minimal inhibitory concentration (MIC), minimal bactericidal concentration (MBC), and log CFU/ml reductions, at their native pH and neutral pH. Each fraction produced significant reductions (P0.05) at the native pH: MICs for sugars plus organic, phenolics, and anthocyanins were 5.6/2.6 Brix/acid (citric acid equivalents) 2.70g/L (gallic acid equivalent), and 14.80mg/L (cyanidin-3-glucoside equivalent), respectively. Sugars plus organic acids at native pH (3) produced a reduction below detectable limits (1 log CFU/ml) compared to the control at 24h for 11.3/5.2 and 5.6/2.6 Brix/acid. Phenolics at native pH (4) produced reductions below detectable limits compared to the control at 24h and initial inocula for treatments of 5.40 and 2.70g/L. Anthocyanins at native pH (2) produced reductions below detectable limits for treatments of 29.15 and 14.80mg/L cyanidin-3-glucoside equivalents. Neutralized phenolics and anthocyanins had the same MIC and MBC as those at their native pH. Neutralized sugars plus organic acids did not inhibit bacterial growth compared to the control. Neutralized phenolics reduced bacteria below detectable limits in treatments of 5.40g/L and 2.70g/L compared to the control. Neutralized anthocyanins reduced bacterial growth below detectable limits at the concentration of 29.15mg/L, but at 14.80mg/L there was no significant reduction. Stationary-phase cells of E. coli O157:H7 were treated with 5% of each fraction in 0.8% NaCl for 20min and viewed under transmission electron microscopy. All fractions caused significant damage compared the control. Sugars plus organic acids caused visible osmotic stress, while phenolics and anthocyanins caused disintegration of the outer membrane.