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2012

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Cranberry juice for the prevention of recurrences of urinary tract infections

Posted
Authors
Salo J, Uhari M, Helminen M, Korppi M, Nieminen T, Pokka T, Kontiokari T
Journal
Clin Infect Dis 54(3):340-6
Abstract

Background. Cranberry juice prevents recurrences of urinary tract infections (UTIs) in adult women. The objective of this study was to evaluate whether cranberry juice is effective in preventing UTI recurrences in children.
Methods. A double-blind randomized placebo-controlled trial was performed in 7 hospitals in Finland. A total of 263 children treated for UTI were randomized to receive either cranberry juice (n = 129) or placebo (n = 134) for 6 months. Eight children were omitted because of protocol violations, leaving 255 children for the final analyses. The children were monitored for 1 year, and their recurrent
UTIs were recorded. Results. Twenty children (16%) in the cranberry group and 28 (22%) in the placebo group had at least 1 recurrent UTI (difference, -6%; 95% confidence interval [CI], -16 to 4%; P = .21). There were no differences in timing between these first recurrences (P = .32). Episodes of UTI totaled 27 and 47 in the cranberry and placebo groups, respectively, and the UTI incidence density per person-year at risk was 0.16 episodes lower in the cranberry group (95% CI, -.31 to -.01; P = .035). The children in the cranberry group had significantly fewer days on antimicrobials (-6 days per patient-year; 95% CI, -7 to -5; P .001). Conclusions. The intervention did not significantly reduce the number of children who experienced a recurrence of UTI, but it was effective in
reducing the actual number of recurrences and related antimicrobial use.

Cranberry Proanthocyanidins: Natural Weapons against Periodontal Diseases

Posted
Authors
Feghali K, Feldman M, La VD, Santos J, Grenier D
Journal
J Agric Food Chem Nov 29. [Epub ahead of print]
Abstract

Cranberry ( Vaccinium macrocarpon ) is known to have a beneficial effect on several aspects of human health. Proanthocyanidins (PACs), the most abundant flavonoids extracted from red cranberry fruits, have been reported to possess antimicrobial, antiadhesion, antioxidant, and anti-inflammatory properties. Recent in vitro studies have shown that cranberry PACs may be potential therapeutic agents for the prevention and management of periodontitis, an inflammatory disease of bacterial origin affecting tooth-supporting tissues. After presenting an overview of cranberry phytochemicals and their potential for human health benefits, this review will focus on the effects of cranberry PACs on connective tissue breakdown and alveolar bone destruction, as well as their potential for controlling periodontal diseases. Possible mechanisms of action of cranberry PACs include the inhibition of (i) bacterial and host-derived proteolytic enzymes, (ii) host inflammatory response, and (iii) osteoclast differentiation and activity. Given that cranberry PACs have shown interesting properties in in vitro studies, clinical trials are warranted to better evaluate the potential of these molecules for controlling periodontal diseases.

Inhibition of Adhesion of Uropathogenic Escherichia coli Bacteria to Uroepithelial Cells by Extracts from Cranberry

Posted
Authors
Ermel G, Georgeault S, Inisan C, Besnard M
Journal
J Med Food 15(2):126-34
Abstract

ABSTRACT Cranberry extract has been reported as a therapeutic agent, mainly in urinary tract infections due to its antiadhesive capacity. In order to compare the effects of proanthocyanidin (procyanidin) (PAC)-standardized cranberry extracts and commercial PAC A2, we first investigated the presence of genes encoding known adhesins on 13 strains of uropathogenic strains coming from patients with cystisis. After this characterization, the anti-adhesive effects of PAC A2 were assayed on selected uropathogenic Escherichia coli strains before testing cranberry extracts. Before checking inhibitory effect on bacterial adhesion to cells, we showed that neither PAC A2 or three cranberry extracts (A, B, and C) specifically inhibited the growth and did not supply any potential nutrient to E. coli strains, including the unrelated control strain. PAC A2 exhibited an inhibitory effect on the adhesion of two selected uropathogenic strains of E. coli. This work also showed that a preliminary exposure of bacteria to PAC A2 significantly reduced the adhesion. This phenomenon has been also observed with a lesser impact when uroepithelial cells were pretreated with PAC A2. Moreover, the assays were more robust when bacteria were in fast growing conditions (exponential phase): the adhesion to uroepithelial cells was greater. Significant reduction of adhesion to urepithelial cells was observed: around 80% of inhibition of adhesion with the cranberry extracts at equivalent PAC concentration of 50 µg/mL. The effects of the different assayed extracts were not obviously different except for extract B, which inhibited approximately 55% of adhesion at an equivalent PAC concentration of 5 µg/mL

Isolation and identification of intestinal CYP3A inhibitors from cranberry (Vaccinium macrocarpon) using human intestinal microsomes

Posted
Authors
Kim E, Sy-Cordero A, Graf TN, Brantley SJ, Paine MF, Oberlies NH
Journal
Planta Med. 77(3):265-70
Abstract

infections. These individuals are likely to be taking medications concomitantly with cranberry juice, leading to concern about potential drug-dietary substance interactions, particularly in the intestine, which, along with the liver, is rich in expression of the prominent drug metabolizing enzyme, cytochrome P450 3A (CYP3A). Using a systematic in vitro-in vivo approach, a cranberry juice product was identified recently that elicited a pharmacokinetic interaction with the CYP3A probe substrate midazolam in 16 healthy volunteers. Relative to water, cranberry juice inhibited intestinal first-pass midazolam metabolism. In vitro studies were initiated to identify potential enteric CYP3A inhibitors from cranberry via a bioactivity-directed fractionation approach involving dried whole cranberry [Vaccinium macrocarpon Ait. (Ericaceae)], midazolam, and human intestinal microsomes (HIM). Three triterpenes (maslinic acid, corosolic acid, and ursolic acid) were isolated. The inhibitory potency (IC(50)) of maslinic acid, corosolic acid, and ursolic acid was 7.4, 8.8, and 10 microM, respectively, using HIM as the enzyme source and 2.8, 4.3, and 10 microM, respectively, using recombinant CYP3A4 as the enzyme source. These in vitro inhibitory potencies, which are within the range of those reported for two CYP3A inhibitory components in grapefruit juice, suggest that these triterpenes may have contributed to the midazolam-cranberry juice interaction observed in the clinical study.

Low-energy cranberry juice decreases lipid oxidation and increases plasma antioxidant capacity in women with metabolic syndrome

Posted
Authors
Basu A, Betts NM, Ortiz J, Simmons B, Wu M, Lyons TJ
Journal
Nutr Res 31(3):190-6
Abstract

Cranberries, high in polyphenols, have been associated with several cardiovascular health benefits, although limited clinical trials have been reported to validate these findings. We tested the hypothesis that commercially available low-energy cranberry juice (Ocean Spray Cranberries, Inc, Lakeville-Middleboro, Mass) will decrease surrogate risk factors of cardiovascular disease, such as lipid oxidation, inflammation, and dyslipidemia, in subjects with metabolic syndrome. In a randomized, double-blind, placebo-controlled trial, participants identified with metabolic syndrome (n = 15-16/group) were assigned to 1 of 2 groups: cranberry juice (480 mL/day) or placebo (480 mL/day) for 8 weeks. Anthropometrics, blood pressure measurements, dietary analyses, and fasting blood draws were conducted at screen and 8 weeks of the study. Cranberry juice significantly increased plasma antioxidant capacity (1.5 +/- 0.6 to 2.2 +/- 0.4 mumol/L [means +/- SD], P .05) and decreased oxidized low-density lipoprotein and malondialdehyde (120.4 +/- 31.0 to 80.4 +/- 34.6 U/L and 3.4 +/- 1.1 to 1.7 +/- 0.7 mumol/L, respectively [means +/- SD], P .05) at 8 weeks vs placebo. However, cranberry juice consumption caused no significant improvements in blood pressure, glucose and lipid profiles, C-reactive protein, and interleukin-6. No changes in these parameters were noted in the placebo group. In conclusion, low-energy cranberry juice (2 cups/day) significantly reduces lipid oxidation and increases plasma antioxidant capacity in women with metabolic syndrome. Copyright Copyright 2011 Elsevier Inc. All rights reserved.

MicroRNA alterations in Barrett's esophagus, esophageal adenocarcinoma, and esophageal adenocarcinoma cell lines following cranberry extract treatment: Insights for chemoprevention

Posted
Authors
Kresty LA, Clarke J, Ezell K, Exum A, Howell AB, Guettouche T
Journal
J Carcinog 10:34. Epub 2011 Dec 22
Abstract

BACKGROUND: Aberrant expression of small noncoding endogenous RNA molecules known as microRNAs (miRNAs) is documented to occur in multiple cancer types including
esophageal adencarcinoma (EAC) and its only known precursor, Barrett's esophagus (BE). Recent studies have linked dysregulation of specific miRNAs to histological
grade, neoplastic progression and metastatic potential.
MATERIALS AND METHODS: Herein, we present a summary of previously reported dysregulated miRNAs in BE and EAC tissues as well as EAC cell lines and evaluate a cranberry proanthocyanidin rich extract's (C-PAC) ability to modulate miRNA expression patterns of three human EAC cell lines (JHEso-Ad-1, OE33 and OE19).
RESULTS: A review of 13 published studies revealed dysregulation of 87 miRNAs in BE and EAC tissues, whereas 52 miRNAs have been reported to be altered in BE or
EAC cell lines, with 48% overlap with miRNA changes reported in tissues. We report for the first time C-PAC-induced modulation of five miRNAs in three EAC
cell lines resulting in 26 validated gene targets and identification of key signaling pathways including p53, angiogenesis, T-cell activation and apoptosis.
Additionally, mutiple cancer related networks were ideintified as modulated by C-PAC utilizing Kyoto Encyclopedia of Genes and Genomes (KEGG), Protein Analysis Through Evolutionary Relationships (PANTHER), and MetaCore analysis tools.
CONCLUSIONS: Study results support the cancer inhibitory potential of C-PAC is in part attributable to C-PAC's ability to modify miRNA profiles within EAC cells. A number of C-PAC-modulated miRNAs have been been identified as dysregulated in BE and EAC. Further insights into miRNA dysregulation and modulation by select cancer preventive agents will support improved targeted interventions in
high-risk cohorts.

North American cranberry (Vaccinium macrocarpon) stimulates apoptotic pathways in DU145 human prostate cancer cells in vitro

Posted
Authors
MacLean MA, Scott BE, Deziel BA, Nunnelley MC, Liberty AM, Gottschall-Pass KT, Neto CC, Hurta RA
Journal
Nutr Cancer. 63(1):109-20
Abstract

Diets rich in fruits and vegetables have been shown to improve patient prognosis in a variety of cancers, a benefit partly derived from phytochemicals, many of which target cell death pathways in tumor cells. Cranberries (Vaccinium macrocarpon) are a phytochemical-rich fruit containing a variety of polyphenolic compounds. As flavonoids have been shown to induce apoptosis in human tumor cells, this study investigated the hypothesis that cranberry-mediated cytotoxicity in DU145 human prostate adenocarcinoma cells involves apoptosis. The results showed that induction of apoptosis in these cells occurred in response to treatment with whole cranberry extract and occurred through caspase-8 mediated cleavage of Bid protein to truncated Bid resulting in cytochrome-C release from the mitochondria. Subsequent activation of caspase-9 ultimately resulted in cell death as characterized by DNA fragmentation. Increased Par-4 protein expression was observed, and this is suggested to be at least partly responsible for caspase-8 activation. Proanthocyanidin-enriched and flavonol-enriched fractions of cranberry also increased caspase-8 and caspase-9 activity, suggesting that these compounds play a possible role in apoptosis induction. These findings indicate that cranberry phytochemicals can induce apoptosis in prostate cancer cells in vitro, and these findings further establish the potential value of cranberry phytochemicals as possible agents against prostate cancer.

Oral consumption of cranberry juice cocktail inhibits molecular-scale adhesion of clinical uropathogenic Escherichia coli.

Posted
Authors
Tao YY, Pinzon-Arango PA, Howell AB, Camesano TA
Journal
J Med Food 14: 7/8, 739-745
Abstract

Cranberry juice cocktail (CJC) has been shown to inhibit the formation of biofilm by uropathogenic Escherichia coli. In order to investigate whether the anti-adhesive components could reach the urinary tract after oral consumption of CJC, a volunteer was given 16 oz of either water or CJC. Urine samples were collected at 0, 2, 4, 6, and 8 hours after consumption of a single dose. The ability of compounds in the urine to influence bacterial adhesion was tested for six clinical uropathogenic E. coli strains, including four P-fimbriated strains (B37, CFT073, BF1023, and J96) and two strains not expressing P-fimbriae but exhibiting mannose-resistant hemagglutination (B73 and B78). A non-fimbriated strain, HB101, was used as a control. Atomic force microscopy (AFM) was used to measure the adhesion force between a silicon nitride probe and bacteria treated with urine samples. Within 2 hours after CJC consumption, bacteria of the clinical strains treated with the corresponding urine sample demonstrated lower adhesion forces than those treated with urine collected before CJC consumption. The adhesion forces continued decreasing with time after CJC consumption over the 8-hour measurement period. The adhesion forces of bacteria after exposure to urine collected following water consumption did not change. HB101 showed low adhesion forces following both water and CJC consumption, and these did not change over time. The AFM adhesion force measurements were consistent with the results of a hemagglutination assay, confirming that oral consumption of CJC could act against adhesion of uropathogenic E. coli.

Proanthocyanidin-rich Extracts from Cranberry Fruit ( Vaccinium macrocarpon Ait.) Selectively Inhibit the Growth of Human Pathogenic Fungi Candida spp. and Cryptococcus neoformans.

Posted
Authors
Patel KD. Scarano FJ. Kondo M. Hurta RA. Neto CC.
Journal
J Agric Food Chem 59(24):12864-73
Abstract

Cranberry ( Vaccinium macrocarpon ) has been shown in clinical studies to reduce infections caused by Escherichia coli and other bacteria, and proanthocyanidins are believed to play a role. The ability of cranberry to inhibit the growth of opportunistic human fungal pathogens that cause oral, skin, respiratory, and systemic infections has not been well-studied. Fractions from whole cranberry fruit were screened for inhibition of five Candida species and Cryptococcus neoformans , a causative agent of fungal meningitis. Candida glabrata , Candida lusitaniae , Candida krusei , and Cryptococcus neoformans showed significant susceptibility to treatment with cranberry proanthocyanidin fractions in a broth microdilution assay, with minimum inhibitory concentrations as low as 1 mug/mL. MALDI-TOF MS analysis of subfractions detected epicatechin oligomers of up to 12 degrees of polymerization. Those containing larger oligomers caused the strongest inhibition. This study suggests that cranberry has potential as an antifungal agent.

Strawberries, Blueberries, and Cranberries in the Metabolic Syndrome: Clinical

Posted
Authors
Basu A, Lyons TJ
Journal
J Agric Food Chem Nov 29. [Epub ahead of print]
Abstract

Emerging science supports therapeutic roles of strawberries, blueberries, and cranberries in metabolic syndrome, a prediabetic state characterized by several cardiovascular risk factors. Interventional studies reported by our group and others have demonstrated the following effects: strawberries lowering total and LDL-cholesterol, but not triglycerides, and decreasing surrogate biomarkers of atherosclerosis (malondialdehyde and adhesion molecules); blueberries lowering systolic and diastolic blood pressure and lipid oxidation and improving insulin resistance; and low-calorie cranberry juice selectively decreasing biomarkers of lipid oxidation (oxidized LDL) and inflammation (adhesion molecules) in metabolic syndrome. Mechanistic studies further explain these observations as up-regulation of endothelial nitric oxide synthase activity, reduction in renal oxidative damage, and inhibition of the activity of carbohydrate digestive enzymes or angiotensin-converting enzyme by these berries. These findings need confirmation in future studies with a focus on the effects of strawberry, blueberry, or cranberry intervention in clinical biomarkers and molecular mechanisms underlying the metabolic syndrome.