BACKGROUND: Cardiometabolic risk is the risk of cardiovascular disease (CVD), diabetes, or stroke, which are leading causes of mortality and morbidity worldwide.
OBJECTIVE: The objective of this study was to determine the potential of low-calorie cranberry juice (LCCJ) to lower cardiometabolic risk.
METHODS: A double-blind, placebo-controlled, parallel-arm study was conducted with controlled diets. Thirty women and 26 men (mean baseline characteristics: 50 y; weight, 79 kg; body mass index, 28 kg/m(2)) completed an 8-wk intervention with LCCJ or a flavor/color/energy-matched placebo beverage. Twice daily volunteers consumed 240 mL of LCCJ or the placebo beverage, containing 173 or 62 mg of phenolic compounds and 6.5 or 7.5 g of total sugar per 240-mL serving, respectively.
RESULTS: Fasting serum triglycerides (TGs) were lower after consuming LCCJ and demonstrated a treatment x baseline interaction such that the participants with higher baseline TG concentrations were more likely to experience a larger treatment effect (1.15 +/- 0.04 mmol/L vs. 1.25 +/- 0.04 mmol/L, respectively; P = 0.027). Serum C-reactive protein (CRP) was lower for individuals consuming LCCJ than for individuals consuming the placebo beverage [ln transformed values of 0.522 +/- 0.115 ln(mg/L) vs. 0.997 +/- 0.120 ln(mg/L), P = 0.0054, respectively, and equivalent to 1.69 mg/L vs. 2.71 mg/L back-transformed]. LCCJ lowered diastolic blood pressure (BP) compared with the placebo beverage (69.2 +/- 0.8 mm Hg for LCCJ vs. 71.6 +/- 0.8 mm Hg for placebo; P = 0.048). Fasting plasma glucose was lower (P = 0.03) in the LCCJ group (5.32 +/- 0.03 mmol/L) than in the placebo group (5.42 +/- 0.03 mmol/L), and LCCJ had a beneficial effect on homeostasis model assessment of insulin resistance for participants with high baseline values (P = 0.035).
CONCLUSION: LCCJ can improve several risk factors of CVD in adults, including circulating TGs, CRP, and glucose, insulin resistance, and diastolic BP. This trial was registered at clinicaltrials.gov as NCT01295684.

OBJECTIVE: In the context of increasing microbial resistance and limited new antimicrobials, we aimed to study the antimicrobial effects of cranberry proanthocyanidin extracts on Escherichia coli growth, adhesion to epithelial cells, and lung infection.
DESIGN: Experimental in vitro and in vivo investigation.
SETTING: University research laboratory.
SUBJECTS: Seventy-eight 6- to 8-week-old male Balb/C mice.
INTERVENTIONS: In vitro, the effect of increasing concentrations of cranberry proanthocyanidin on bacterial growth of different clinical E. coli isolates was evaluated. Ex vivo, adhesion of E. coli to fresh human buccal epithelial cells was measured in the presence or absence of cranberry proanthocyanidin using microscopy. In vivo, lung bacterial count, pulmonary immune response (neutrophil murine chemokine keratinocyte-derived cytokine measurement and polymorphonuclear recruitment in bronchoalveolar lavage fluid), and lethality were evaluated in a pneumonia mouse model with E. coli precultured with or without cranberry proanthocyanidin. E. coli isolates originated from ventilated ICU patients with respiratory tract colonization or ventilator- associated pneumonia. They differed in number of virulence genes.
MEASUREMENTS AND MAIN RESULTS: A significant inhibition of bacterial growth was observed with increasing concentration of cranberry proanthocyanidin, affecting both time to maximal growth and maximal growth rate (p CONCLUSION: Cranberry proanthocyanidins exhibit potent effects on growth, adhesion, and virulence of oropharyngeal and lung isolates of E. coli, suggesting that cranberry proanthocyanidin could be of clinical interest to reduce oropharyngeal colonization and prevent lung infection.

Cranberries (Vaccinium macrocarpon) are a rich source of phenolic phytochemicals, which likely contribute to their putative health benefits. A single-dose pharmacokinetic trial was conducted in 10 healthy adults 50y to evaluate the acute (24-h) absorption and excretion of flavonoids, phenolic acids and proanthocyanidins (PACs) from a low-calorie cranberry juice cocktail (54% juice). Inter-individual variability was observed in the Cmax and Tmax of many of these compounds in both plasma and urine. The sum total concentration of phenolics detected in plasma reached a peak of 34.2mug/ml between 8 and 10h, while in urine this peak was 269.8mug/mg creatinine, and appeared 2-4h earlier. The presence of PAC-A2 dimers in human urine has not previously been reported. After cranberry juice consumption, plasma total antioxidant capacity assessed using ORAC and TAP assays correlated with individual metabolites. Our results show phenolic compounds in cranberry juice are bioavailable and exert antioxidant actions in healthy older adults.

Since polyphenol-rich products such as red wine, grape juice, and grape extracts have been shown to induce potent endothelium-dependent relaxations, we have evaluated whether commercial fruit juices such as those from berries are also able to induce endothelium-dependent relaxations of isolated coronary arteries and, if so, to determine whether this effect is related to their phenolic content. Among the 51 fruit juices tested, 2/12 grape juices, 3/7 blackcurrant juices, 4/5 cranberry juices, 1/6 apple juices, 0/5 orange juices, 2/6 red fruit and berry juices, 3/6 blends of red fruit juices, and 0/4 non-red fruit juices were able to induce relaxations achieving more than 50% at a volume of 1%. The active fruit juices had phenolic contents ranging from 0.31 to 1.86g GAE/L, which were similar to those of most of the less active juices with the exception of one active grape juice (2.14g GAE/L) and one active blend of red fruit juices (3.48g GAE/L). Altogether, these findings indicate that very few commercial fruit juices have the ability to induce potent endothelium-dependent relaxations, and that this effect is not related to their quantitative phenolic content, but rather to their qualitative phenolic composition.

Cranberry flavonoids (flavonols and flavan-3-ols), in addition to their antioxidant properties, have been shown to possess potential in vitro activity against several cancers. However, the difficulty of isolating cranberry compounds has largely limited anticancer research to crude fractions without well-defined compound composition. In this study, individual cranberry flavonoids were isolated to the highest purity achieved so far using gravity and high performance column chromatography and LC-MS characterization. MTS assay indicated differential cell viability reduction of SKOV-3 and OVCAR-8 ovarian cancer cells treated with individual cranberry flavonoids. Treatment with quercetin aglycone and PAC DP-9, which exhibited the strongest activity, induced apoptosis, led to caspase-3 activation and PARP deactivation, and increased sensitivity to cisplatin. Furthermore, immunofluorescence microscopy and western blot study revealed reduced expression and activation of epidermal growth factor receptor (EGFR) in PAC DP-9 treated SKOV-3 cells. In addition, quercetin aglycone and PAC DP-9 deactivated MAPK-ERK pathway, induced downregulation of cyclin D1, DNA-PK, phospho-histone H3 and upregulation of p21, and arrested cell cycle progression. Overall, this study demonstrates promising in vitro cytotoxic and anti-proliferative properties of two newly characterized cranberry flavonoids, quercetin aglycone and PAC DP-9, against ovarian cancer cells.

BACKGROUND: Elemental enteral nutrition (EEN) decreases gut-associated lymphoid tissue (GALT) function, including fewer Peyer's patch lymphocytes and lower levels of the tissue T helper 2 (Th2) cytokines and mucosal transport protein polymeric immunoglobulin receptor (pIgR), leading to lower luminal secretory immunoglobulin A (sIgA) levels. Since we recently demonstrated that cranberry proanthocyanidins (PACs) maintain the Th2 cytokine interleukin (IL)-4 when added to EEN, we hypothesized the addition of PACs to EEN would normalize other GALT parameters and maintain luminal levels of sIgA.

METHODS: Institute of Cancer Research mice were randomized (12/group) to receive chow, EEN, or EEN + PACs (100 mg/kg body weight) for 5 days, starting 2 days after intragastric cannulation. Ileum tissue was collected to measure IL-4 by enzyme-linked immunosorbent assay, pIgR by Western blot, and phosphorylated STAT-6 by microarray. Intestinal wash fluid was collected to measure sIgA by Western blot.

RESULTS: Compared with chow, EEN significantly decreased tissue IL-4, phosphorylated STAT-6, and pIgR. The addition of PACs to EEN prevented these alterations. Compared with chow, EEN resulted in significantly lower levels of luminal sIgA. The addition of PACs to EEN increased luminal sIgA levels compared with EEN alone.

CONCLUSIONS: This study suggests the addition of PACs to EEN may support GALT function and maintain intestinal sIgA levels compared with EEN administration alone.

BACKGROUND AND OBJECTIVE: In periodontitis, gingival epithelial cells can produce interleukin (IL)-6, a regulator of osteoclastic bone resorption, in response to IL-1beta. IL-1beta regulates cytokine expression via signaling pathways, including nuclear factor (NF)-B and mitogen activated protein kinase (MAPK)/activator protein (AP)-1. Cranberry proanthocyanidins (PACs) inhibit IL-1beta-stimulated IL-6 production, but specific mechanisms are unclear. The objectives of this study were to determine effects of cranberry PACs on NF-B and MAPK/AP-1 activation of IL-1beta-stimulated IL-6 production in gingival epithelial cells.

MATERIAL AND METHODS: Cranberry high molecular weight non-dialyzable material (NDM), rich in PACs, was derived from cranberry juice. Human gingival epithelial cells [Smulow-Glickman (S-G)] were incubated with IL-1beta in the presence or absence of NDM or inhibitors of NF-B, [nemo-binding domain (NBD) peptide] or AP-1 (SP600125), and IL-6 levels were measured by ELISA. Effects of NDM on IL-1beta-activated NF-B and AP-1 and phosphorylated intermediates in both pathways were measured in cell extracts via binding to specific oligonucleotides and specific sandwich ELISAs, respectively. Data were analyzed using ANOVA and Scheffe's F procedure for post hoc comparisons.

RESULTS: IL-1beta (> 0.1 nm) caused a time- and dose-dependent stimulation of S-G epithelial cell IL-6 production (p

CONCLUSION: In S-G epithelial cells, IL-1beta appeared to upregulate IL-6 production via activation of both NF-B and MAPK/AP-1 signaling pathways because cranberry NDM decreased nuclear levels of IL-1beta-activated NF-B (p65) and AP-1 (phospho-c-Jun) and strongly inhibited IL-6 production. Lack of inhibition of phosphorylation of IBalpha, c-Jun or ERK1/2 suggested that NDM might affect both pathways downstream from those points in S-G cells, such as ubiquitination and proteosomal degradation of IBalpha, or inhibition of nuclear activity of c-Jun and/or ERK1/2. Defining these points of inhibition precisely may help identify molecular targets of cranberry polyphenols. 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

In the context of dental caries prevention by natural foodstuff sources, antifungal and antibiofilm activities of dry commercial extracts of cranberry fruit (Vaccinium macrocarpon Aiton) and two other red fruits (Vaccinium myrtillus L. and Malpighia punicifolia L.) were assessed on Candida albicans and Candida glabrata yeasts. When added to the culture medium, the cranberry extract displayed a significant anti-adhesion activity against Candida spp. when used at low concentrations. In addition, the pretreatment of surfaces with this extract induced an anti-adhesion activity mainly against C. glabrata yeasts and an antibiofilm activity against C. albicans. This activity was dependent on concentration, species, and strain. A phytochemical investigation bioguided by anti-adhesion tests against the two Candida species was carried out on crude cranberry juice to determine the active fractions. Three subfractions enriched in proanthocyanidins showed an anti-adhesion activity at low concentrations. This study investigated for the first time the interest of crude extracts of cranberry and cranberry juice fractions to prevent biofilms of C. glabrata. It highlighted the potency of consuming this fruit and using it as a source of anti-adhesion agents. 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

Abstract: We examined how intake of polyphenols modifies brachial artery flow-mediated dilation (FMD) at rest, and cycling anaerobic performance, in elite athletes. In the first randomized cross-over study, FMD was measured over a three-hour period on two occasions in eight elite male and female athletes after acute consumption of either polyphenols from cranberries and grape seeds (600 mg) or a polyphenol-free placebo drink. Consumption of the polyphenol-rich drink led to a significant increase in FMD compared to placebo (p = 0.02), with a peak at 60 min. In a second study, 12 elite male and female athletes completed a three-kilometer time trial (TT) on an ergocycle on two occasions in random order, either after consumption of 800 mg of polyphenols or a placebo. Acute intake of the polyphenol extract had no impact on the three-kilometer time trial completion. However, plasma lactate levels were significantly lower before and after the TT when subjects consumed the polyphenols vs. placebo (p

BACKGROUND AND OBJECTIVE: Gingival epithelial cells and fibroblasts participate in periodontal inflammation and destruction, producing interleukin (IL)-6, a regulator of osteoclastic bone resorption, and the neutrophil chemoattractant IL-8. IL-17, a product of T-helper 17 cells, may play a role in periodontitis by stimulating cytokine production by gingival cells. The cranberry (Vaccinium macrocarpon) is rich in polyphenols, particularly proanthocyanidins, which have antioxidant and other beneficial properties. Cranberry components inhibit pro-inflammatory activities of lipopolysaccharide-stimulated human macrophages, gingival fibroblasts, and epithelial cells, but little is known of its effects on IL-17-stimulated cytokine production. The objectives were to determine the effects of IL-17 + cranberry components on IL-6 and IL-8 production by human gingival epithelial cells and fibroblasts.

MATERIAL AND METHODS: Cranberry high molecular weight non-dialyzable material (NDM), which is rich in proanthocyanidins, was derived from cranberry juice. Human gingival epithelial cells and normal human gingival fibroblasts were incubated with NDM (5-50 mug/mL), IL-17 (0.5-100 ng/mL), or NDM + IL-17 in serum-free medium for 6 d. IL-6 and IL-8 in culture supernatants were measured by ELISA. Membrane damage and viability were assessed by lactate dehydrogenase activity released into cell supernatants and activity of a mitochondrial enzyme, respectively. Data were analyzed using ANOVA and Scheffe's F procedure for post hoc comparisons.

RESULTS: In both cell lines, IL-17 (> ~5-10 ng/mL) significantly stimulated production of IL-6 (p

CONCLUSION: Cranberry NDM inhibition of constitutive and IL-17-stimulated IL-6 and IL-8 production by gingival fibroblasts and epithelial cells suggests that cranberry components could be useful as a host modulatory therapeutic agent to prevent or treat periodontitis. 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.