Cranberry-lingonberry juice (CLJ) was effective in preventing urinary tract infections (UTIs) in our earlier randomized clinical trial. We aimed to test whether consumption of CLJ at a similar dose to earlier reduces the biofilm formation and virulence of uropathogenic Escherichia coli in urine. Twenty healthy women drank 100 ml of CLJ daily for two weeks. Urine samples were obtained 2–4 hours after the last dose. Control samples were taken after a one-week period without berry consumption. Biofilm formation of 20 E. coli strains was measured at 72 hours by the polystyrene microtitre plate method. Quantitative real-time PCR analyses were performed for selected genes. Four of the 20 clinical strains produced more biofilm in urine after CLJ consumption (P  0.05) and one produced less. Expression levels of the pga, cpxA, fimA and papF genes did not differ between bacteria grown in control urine and urine obtained after CLJ consumption, except for pga gene expression, which was reduced in one strain after CLJ (P = 0.04). It appears that the effect of CLJ in preventing UTIs is not explained by mechanisms that reduce biofilm formation or the expression of selected virulence genes of Escherichia coli in urine.

Cranberry ( Vaccinium macrocarpon ) products have been widely recommended in traditional American medicine for the treatment of urinary tract infection (UTI). A total of 19 different commercial cranberry products from American and European markets have been analyzed by different global phenolic methods and by UPLC-DAD-ESI-TQ MS. In addition, in vitro antioxidant capacity and uropathogenic bacterial antiadhesion activity tests have been performed. Results revealed that products found in the market widely differed in their phenolic content and distribution, including products completely devoid of flavan-3-ols to highly purified ones, either in A-type proanthocyanidins (PACs) or in anthocyanins. The product presentation form and polyphenolic profile widely affected the antiadhesion activity, ranging from a negative (nulel) effect to a MIC = 0.5 mg/mL for cranberry powders and a MIC=112 mg/mL for gel capsule samples. Only 4 of 19 products would provide the recommended dose of intake of 36 mg total PACs/day. Of most importance was the fact that this dose would actually provide as low as 0.00 and up to 205 μg/g of procyanidin A2, indicating the lack of product standardization and incongruence between global and individual compound analysis.

ABSTRACT: BACKGROUND: Oral candidiasis is a common fungal disease mainly caused by Candida albicans. The aim of this study was to investigate the effects of A-type cranberry proanthocyanidins (AC-PACs) on pathogenic properties of C. albicans as well as on the inflammatory response of oral epithelial cells induced by this oral pathogen. METHODS: Microplate dilution assays were performed to determine the effect of AC-PACs on C. albicans growth as well as biofilm formation stained with crystal violet. Adhesion of FITC-labeled C. albicans to oral epithelial cells and to acrylic resin disks was monitored by fluorometry. The effects of AC-PACs on C. albicans-induced cytokine secretion, nuclear factor-kappa B (NF-kappaB) p65 activation and kinase phosphorylation in oral
epithelial cells were determined by immunological assays. RESULTS: Although AC-PACs did not affect growth of C. albicans, it prevented biofilm formation and reduced adherence of C. albicans to oral epithelial cells and saliva-coated acrylic resin discs. In addition, AC-PACs significantly decreased the secretion of IL-8 and IL-6 by oral epithelial cells stimulated with C. albicans. This
anti-inflammatory effect was associated with reduced activation of NF-kappaB p65 and phosphorylation of specific signal intracellular kinases. CONCLUSION: AC-PACs by affecting the adherence properties of C. albicans and attenuating the inflammatory response induced by this pathogen represent potential novel therapeutic agents for the prevention/treatment of oral candidiasis.

Proanthocyanidin is commonly used for inhibiting urinary tract infection (UTI) of sensitive strains of Escherichia coli. The aim of this study was to investigate the effect of proanthocyanidin on adherence of uropathogenic multi-drug resistant E. coli to uroepithelial cells, which has not yet been investigated so far. Extracts of the purified proanthocyanidin were prepared from dried cranberry juice. Purity and structural assignment of proanthocyanidin was assessed using high performance liquid chromatography and (13)C nuclear magnetic resonance spectroscopy, respectively. Subsequently, its affect on multi-drug resistant bacteria as well as quantification of anti-adherence bioactivity on human vaginal and bladder epithelial cells was appraised. Inhibition of adherence to an extent of about 70% with multi-drug resistant E. coli strains was observed on uroepithelial cell. The anti-adherence bioactivity of the proanthocyanidin was detected at concentrations of 10-50 µg/ml with significant bacteriuria. Probable proanthocyanidin through A-type linkages either combines to P-fimbriae of bacterial cells or modifies the structural entity of P-fimbriae and inhibits bacterial adherence to uroepithelial cells. The proanthocyanidin exhibited anti-adherence property with multi-drug resistant strains of uropathogenic P-fimbriated E. coli with in vitro study. Hence proanthocyanidin may be considered as an inhibitory agent for multi-drug resistant strains of E. coli adherence to uroepithelial cells.

Previous studies demonstrated that a cranberry high-molecular-mass, nondialyzable material (NDM) can inhibit adhesion of numerous species of bacteria and prevents bacterial coaggregation of bacterial pairs. Bacterial coaggregation leads to plaque formation leading to biofilm development on surfaces of oral cavity. In the present study, we evaluated the effect of low concentrations of NDM on Streptococcus gordonii metabolic activity and biofilm formation on restorative dental surfaces. We found that the NDM selectively inhibited metabolic activity of S. gordonii, without affecting bacterial viability. Inhibiting the metabolic activity of bacteria in biofilm may benefit the health of the oral cavity.

OBJECTIVE:
To compare the time to urinary tract infection (UTI) and the rates of asymptomatic bacteriuria and urinary P-fimbriated Escherichia coli during a 6-month period in women ingesting cranberry vs placebo juice daily.
PATIENTS AND METHODS:
Premenopausal women with a history of recent UTI were enrolled from November 16, 2005, through December 31, 2008, at 2 centers and randomized to 1 of 3 arms: 4 oz of cranberry juice daily, 8 oz of cranberry juice daily, or placebo juice. Time to UTI (symptoms plus pyuria) was the main outcome. Asymptomatic bacteriuria, adherence, and adverse effects were assessed at monthly visits.
RESULTS:
A total of 176 participants were randomized (120 to cranberry juice and 56 to placebo) and followed up for a median of 168 days. The cumulative rate of UTI was 0.29 in the cranberry juice group and 0.37 in the placebo group (P=.82). The adjusted hazard ratio for UTI in the cranberry juice group vs the placebo group was 0.68 (95% confidence interval, 0.33-1.39; P=.29). The proportion of women with P-fimbriated urinary E coli isolates during the intervention phase was 10 of 23 (43.5%) in the cranberry juice group and 8 of 10 (80.0%) in the placebo group (P=.07). The mean dose adherence was 91.8% and 90.3% in the cranberry juice group vs the placebo group. Minor adverse effects were reported by 24.2% of those in the cranberry juice group and 12.5% in the placebo group (P=.07).
CONCLUSION:
Cranberry juice did not significantly reduce UTI risk compared with placebo. The potential protective effect we observed is consistent with previous studies and warrants confirmation in larger, well-powered studies of women with recurrent UTI. The concurrent reduction in urinary P-fimbriated E coli strains supports the biological plausibility of cranberry activity.
TRIAL REGISTRATION:
clinicaltrials.gov Identifier: NCT00128128.

Consumption of cranberries is known to exert positive health effects, especially against urinary tract infections. For this reason, presumably, they are widely used in folk medicine. Different aspects of cranberry phenolics activity were studied in individual papers but complex study in this matter is missing. The aim of the present study is to provide complex data concerning various aspects of cranberry extract activity. We studied the effects of subinhibitory concentrations of commercially available extract (Żuravit S·O·S(®)) against two Escherichia coli strains isolated from urine of patients with pyelonephritis. Additionally the main extract anthocyanins were characterized. The activity of extract against lipid peroxidation and its radical scavenging ability were also assessed. Żuravit S·O·S(®) decreased the hydrophobicity of one of the studied E. coli strains, reduced swimming motility and adhesion to epithelial cells of both studied strains, it also limited the ability of bacteria to form biofilm. Expression of curli was not affected by cranberry extract, the assessment of P fimbriae expression was not reliable due to extract-induced agglutination of erythrocytes. Cranberry extract caused filamentation in both studied E. coli strains. It also showed pronounced antioxidant and radical scavenging properties. The properties of the studied cranberry extract show that it could be effectively used in prevention and/or elimination of urinary tract infections, specially the recurrent ones.

The antimicrobial effects of the American cranberry (Vaccinium macrocarpon) on a major food-borne pathogen, Staphylococcus aureus, were investigated using commercially obtained Lakewood® organic cranberry juice and Ocean Spray® cranberry juice cocktail and four other berry fruit extracts (acai berry, strawberry, raspberry, and blueberry). The results showed that cranberry is a potent antimicrobial against S. aureus and the most potent among the berries studied. The order of percentage inhibition of bacterial growth at the same concentration of phenolic materials as gallic acid equivalents was Lakewood cranberry juice > Ocean Spray cranberry juice ≫ blueberry > acai berry ≫ raspberry ≫ strawberry. The antimicrobial effect was not due to the acidity of the berries as NaOH-neutralized samples were almost as effective in terms of percentage inhibition of viable cell growth. Solid-phase extraction of cranberry juice using C18 solid phase showed that the antimicrobial effects reside exclusively with the C18-bound materials.

Urinary tract infections (UTIs) represent a recurrent health problem especially for women. More than 50% of women will suffer from a UTI at least once in their lifetime. Cranberries have long been used for their beneficial effects in preventing symptomatic UTIs in several published studies. However, cranberry products used in these clinical studies do not indicate the amount of active ingredients delivered that help to prevent UTIs. Therefore, a dose-dependent study was designed to understand the impact and safety profile of a standardized cranberry product (Proanthocyanidins Standardized Whole Cranberry Powder,PS-WCP) on reducing the recurrences of symptomatic UTI in culture-positive subjects. A 90- day randomized clinical trial including an untreated control group with a total of 60 female subjects between 18-40 years of age was conducted. Study subjects were randomly selected and assigned to three groups including an untreated control group (n=16), a low dose (500 mg daily, n=21) and a high dose (1000 mg daily, n=23) treatment group. The safety of PSWCP was assessed by evaluation of biochemical and hematological parameters on days 10, 30, 60 and 90 during the study, comparing the values with those at the baseline. Occurrence of UTI at baseline and during the follow-up period was characterized by the presence of symptoms and Escherichia coli in the culture of urine samples. The statistical analysis used was ANOVA. At the end of the 90-day treatment period, no significant changes were observed in the hematological and serum biochemical parameters. At the end of the study, change in the presence of E. coli in the untreated control group was not significant (p=0.7234), whereas, there was significant reduction (p0.05) in the subjects positive for E. coli in both the high dose and low dose treatment groups, compared to baseline evaluation. Symptomatic relief was also reported in the low and high dose treatment groups, while none was reported by subjects in the untreated control group. In conclusion, PS-WCP was effective in safely reducing the number of E. coli positive subjects at both the 500 mg and 1000 mg dose levels and in ameliorating the symptoms of UTI in these subjects. Therefore, a daily dose of 500 mg or 1000 mg of PS-WCP may be considered as an adjunct to antibiotic prophylactic therapy against recurrent UTIs.

Absorption and excretion of twenty cranberry-derived phenolics were studied following the consumption of cranberry juice, sauces, and fruits by healthy human volunteers. Plasma and urine samples were collected and analysed by gas chromatography–mass spectrometry (GC–MS). A high performance liquid chromatography (HPLC) method was employed for analysing urinary creatinine, which was used as a normalisation agent. Significant increases in the sum of plasma phenolics were observed with different concentration peaks (between 0.5 and 2 h) for individual subjects. Some of the phenolics, such as trans-cinnamic, vanillic, p-coumaric acids, and catechin showed second plasma concentration peaks. All of cranberry-derived phenolics increased significantly in urine samples after the intake of each cranberry product. The high molecular weight quercetin and myricetin, which were abundant in cranberry foodstuffs, were not found in either plasma or urine samples. This study provided the fundamental information for understanding the absorption and excretion of phenolics in the human gastrointestinal system after dietary intake of cranberry products.