The protective effect of proanthocyanidin-containing polyphenol extracts from apples, avocados, cranberries, grapes, or proanthocyanidin microbial metabolites was evaluated in colonic epithelial cells exposed to p-cresol, a deleterious compound produced by the colonic microbiota from L-tyrosine. In HT29 Glc-/+ cells, p-cresol significantly increased LDH leakage and decreased ATP contents, whereas in Caco-2 cell monolayers, it significantly decreased the transepithelial electrical resistance and increased the paracellular transport of FITC-dextran. The alterations induced by p-cresol in HT29 Glc-/+ cells were prevented by the extracts from cranberries and avocados, whereas they became worse by extracts from apples and grapes. The proanthocyanidin bacterial metabolites decreased LDH leakage, ameliorating cell viability without improving intracellular ATP. All of the polyphenol extracts and proanthocyanidin bacterial metabolites prevented the p-cresol-induced alterations of barrier function. These results suggest that proanthocyanidin-containing polyphenol extracts and proanthocyanidin metabolites likely contribute to the protection of the colonic mucosa against the deleterious effects of p-cresol.

Berries are a rich source of (poly)phenols, including anthocyanins, flavan-3-ols, procyanidins, flavonols, ellagitannins, and hydroxycinnamates. Epidemiological evidence indicates that the cardiovascular health benefits of diets rich in berries are related to their (poly)phenol content. These findings are supported by small-scale randomized controlled studies (RCTs) that have shown improvements in several surrogate markers of cardiovascular risk such as blood pressure, endothelial function, arterial stiffness, and blood lipids after acute and short-term consumption of blueberries, strawberries, cranberries, or purified anthocyanin extracts in healthy or diseased individuals. However, firm conclusions regarding the preventive value of berry (poly)phenols cannot be drawn due to the small number of existing studies and limitations that apply to the available data, such as lack of controls or failure to assess the absorption and metabolism of (poly)phenols. Although the current evidence is promising, more long-term RCTs are needed to establish the role of berry (poly)phenols to support cardiovascular health.

The preventive effects of the American cranberry (Vaccinium macrocarpon) against urinary tract infections are supported by extensive studies which have primarily focused on its phenolic constituents. Herein, a phenolic-free carbohydrate fraction (designated cranf1b-F2) was purified from cranberry fruit using ion exchange and size exclusion chromatography. MALDI-TOF-MS analysis revealed that the cranf1b-F2 constituents are predominantly oligosaccharides possessing various degrees of polymerisation and further structural analysis (by GC-MS and NMR) revealed mainly xyloglucan and arabinan residues. In antimicrobial assays, cranf1b-F2 (at 1.25 mg/mL concentration) reduced biofilm production by the uropathogenic Escherichia coli CFT073 strain by over 50% but did not inhibit bacterial growth. Cranf1b-F2 (ranging from 0.625 to 10 mg/mL) also inhibited biofilm formation of the non-pathogenic E. coli MG1655 strain up to 60% in a concentration-dependent manner. These results suggest that cranberry oligosaccharides, in addition to its phenolic constituents, may play a role in its preventive effects against urinary tract infections.

A novel methodology was developed to elucidate proanthocyanidins (PAC) interaction with extra-intestinal pathogenic Escherichia coli (ExPEC). PAC inhibit ExPEC invasion of epithelial cells and, therefore, may prevent transient gut colonization, conferring protection against subsequent extra-intestinal infections, such as urinary tract infections. Until now PAC have not been chemically labeled with fluorophores. In this work, cranberry PAC were labeled with 5-([4,6-dichlorotriazin-2-yl]amino) fluorescein (DTAF), detected by high-performance liquid chromatography with diode-array detection and characterized by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). We report single and double fluorescent-labeled PAC with one or two chlorine atoms displaced from DTAF in alkaline pH via nucleophilic substitution. Fluorescent labeling was confirmed by fragmentation experiments using MALDI-TOF/TOF MS. Fluorescent labeled PAC were able to promote ExPEC agglutination when observed with fluorescence microscopy. DTAF tagged PAC may be used to trace the fate of PAC after they agglutinate ExPEC and follow PAC-ExPEC complexes in cell culture assays.

Respiratory viruses are a major public health problem because of their prevalence and high morbidity rate leading to considerable social and economic implications. Cranberry has therapeutic potential attributed to a comprehensive list of phytochemicals including anthocyanins, flavonols, and unique A-type proanthocyanidins. Soy flavonoids, including isoflavones, have demonstrated anti-viral effects in vitro and in vivo. Recently, it was demonstrated that edible proteins can efficiently sorb and concentrate cranberry polyphenols, including anthocyanins and proanthocyanins, providing greatly stabilized matrices suitable for food products. The combination of cranberry and soy phytoactives may be an effective dietary anti-viral resource. Anti-viral properties of both cranberry juice-enriched and cranberry pomace polyphenol-enriched soy protein isolate (CB-SPI and CBP-SPI) were tested against influenza viruses (H7N1, H5N3, H3N2), Newcastle disease virus and Sendai virus in vitro and in ovo. In our experiments, preincubation with CB-SPI or CBP-SPI resulted in inhibition of virus adsorption to chicken red blood cells and reduction in virus nucleic acid content up to 16-fold, however, CB-SPI and CBP-SPI did not affect hemagglutination. Additionally, CB-SPI and CBP-SPI inhibited viral replication and infectivity more effectively than the commercially available anti-viral drug Amizon. Results suggest CB-SPI and CBP-SPI may have preventative and therapeutic potential against viral infections that cause diseases of the respiratory and gastro-intestinal tract.

Flavonoids are important bioactive plant constituents found in abundance in berries, including cranberries. Cranberry beverages have been shown to beneficially impact urinary and cardiovascular health in clinical and observational studies, but their association with anthropometric outcomes is unknown. We examined the association between cranberry juice cocktail (CJC) consumption with flavonoid intake, and cardiometabolic and anthropometric outcomes among adults in the US data for adults (>19 years, n = 10334) were drawn from cross-sectional National Health and Nutrition Examination Survey combined 2005-2008 survey. We hypothesized that CJC consumers will have lower anthropometric measures and healthier cardiometabolic profiles, including lower cholesterol and C-reactive protein (CRP). A CJC consumer (n = 330) was defined as anyone consuming CJC for 2 nonconsecutive 24-hour dietary recalls. We used multivariate linear regression models to examine differences in anthropometric and cardiometabolic outcomes comparing CJC consumers to nonconsumers controlling for important confounders. Consumers drank an average 404 mL (14 fl oz) of CJC for 2 days and did not have higher total energy intakes compared with nonconsumers (mean [SD], 2259 [79] vs 2112 [24], respectively). In fully adjusted models, adult CJC consumers had significantly lower levels of CRP (mean [SD], -0.13 [0.05]; P = .015), results that were strengthened after further adjustment for body mass index (mean [SD], -0.98 [0.04]; P = .027). Trends toward lower weights and lower levels of cholesterol did not reach statistical significance. Intake of cranberry polyphenols may play a role in promoting anti-inflammatory markers among CJC consumers, specifically lowering CRP levels

In this study, we have assessed the phenolic metabolism of a cranberry extract by microbiota obtained from the ascending colon and descending colon compartments of a dynamic gastrointestinal simulator (SHIME). For comparison, parallel fermentations with a grape seed extract were carried out. Extracts were used directly without previous intestinal digestion. Among the 60 phenolic compounds targeted, our results confirmed the formation of phenylacetic, phenylpropionic and benzoic acids as well as phenols such as catechol and its derivatives from the action of colonic microbiota on cranberry polyphenols. Benzoic acid (38.4mug/ml), 4-hydroxy-5-(3'-hydroxyphenyl)-valeric acid (26.2mug/ml) and phenylacetic acid (19.5mug/ml) reached the highest concentrations. Under the same conditions, microbial degradation of grape seed polyphenols took place to a lesser extent compared to cranberry polyphenols, which was consistent with the more pronounced antimicrobial effect observed for the grape seed polyphenols, particularly against Bacteroides, Prevotella and Blautia coccoides-Eubacterium rectale.

The present study was undertaken for further elucidation of the mechanisms of flavonoid biological activity, focusing on the antioxidative and protective effects of cranberry flavonoids in free radical-generating systems and those on mitochondrial ultrastructure during carbon tetrachloride-induced rat intoxication. Treatment of rats with cranberry flavonoids (7mg/kg) during chronic carbon tetrachloride-induced intoxication led to prevention of mitochondrial damage, including fragmentation, rupture and local loss of the outer mitochondrial membrane. In radical-generating systems, cranberry flavonoids effectively scavenged nitric oxide (IC50 =4.4+/-0.4micro g/ml), superoxide anion radicals (IC50 =2.8+/-0.3micro g/ml) and hydroxyl radicals (IC50 =53+/-4micro g/ml). The IC50 for reduction of 1,1-diphenyl-2-picrylhydrazyl radicals (DPPH) was 2.2+/-0.3micro g/ml. Flavonoids prevented to some extent lipid peroxidation in liposomal membranes and glutathione oxidation in erythrocytes treated with UV irradiation or organic hydroperoxides as well as decreased the rigidity of the outer leaflet of the liposomal membranes. The hepatoprotective potential of cranberry flavonoids could be due to specific prevention of rat liver mitochondrial damage. The mitochondria-addressed effects of flavonoids might be related both to radical-scavenging properties and modulation of various mitochondrial events.

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 (p0.0001 for both). The minimal concentration at which this effect occurred was 250 mug/mL. Cranberry proanthocyanidin significantly reduced E. coli adhesion to fresh buccal epithelial cells by up to 80% (p0.001). Bacterial counts in homogenized lungs and bronchoalveolar lavage fluid were decreased after cranberry proanthocyanidin exposition (p0.05 and p0.01, respectively). Cranberry proanthocyanidin also decreased KC concentrations and polymorphonuclear cell recruitment in bronchoalveolar lavage fluid (p0.05 for both). At identical inoculum, mortality was reduced by more than half in mice inoculated with E. coli exposed to cranberry proanthocyanidin (p0.01).
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.