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.

Lower urinary tract symptoms (LUTS) and benign prostatic hyperplasia increase with age. To date, several medications are available to treat LUTS, including herbal remedies which offer less side effects but lack robust efficacy studies.
This 6-month, randomized, double-blind, placebo-controlled study aimed at evaluating the dose effect of 250 or 500 mg cranberry powder (Flowens™) on LUTS and uroflowmetry in men over the age of 45. A total of 124 volunteers with PSA levels 2.5 ng/mL and an international prostate symptoms score (IPSS) score ≥8 were recruited and randomized. The primary outcome measure was the IPSS, evaluated at 3 and 6 months. Secondary outcome measures included quality of life, bladder volume (Vol), maximum urinary flow rate (Q max), average urinary flow rate (Q ave), ultrasound-estimated post-void residual urine volume (PVR), serum prostate-specific antigen, selenium, interleukin 6, and C-reactive protein at 6 months.
After 6 months, subjects in both Flowens™ groups had a lower IPSS (-3.1 and -4.1 in the 250- and 500-mg groups, p = 0.05 and p 0.001, respectively) versus the placebo group (-1.5), and a dose-response effect was observed. There were significant differences in Q max, Q ave, PVR, and Vol in the Flowens™ 500-mg group versus baseline (p 0.05). A dose-dependent effect on Vol was observed, as well as on PVR, for participants with a nonzero PVR. There was no effect on clinical chemistry or hematology markers.
Flowens™ showed a clinically relevant, dose-dependent, and significant reduction in LUTS in men over 45.

OBJECTIVE: The risk of urinary tract infection (UTI) among women undergoing elective gynecological surgery during which a catheter is placed is high: 10-64% following catheter removal. We conducted the first randomized, double-blind, placebo-controlled trial of the therapeutic efficacy of cranberry juice capsules in preventing UTI after surgery.
STUDY DESIGN: We recruited patients from a single hospital between August 2011 and January 2013. Eligible participants were undergoing elective gynecological surgery that did not involve a fistula repair or vaginal mesh removal. One hundred sixty patients were randomized and received 2 cranberry juice capsules 2 times a day, equivalent to 2 8 ounce servings of cranberry juice, for 6 weeks after surgery or matching placebo. The primary endpoint was the proportion of participants who experienced clinically diagnosed and treated UTI with or without positive urine culture. Kaplan-Meier plots and log rank tests compared the 2 treatment groups.
RESULTS: The occurrence of UTI was significantly lower in the cranberry treatment group compared with the placebo group (15 of 80 [19%] vs 30 of 80 [38%]; odds ratio, 0.38; 95% confidence interval, 0.19-0.79; P = .008). After adjustment for known confounders, including the frequency of intermittent self-catheterization in the postoperative period, the protective effects of cranberry remained (odds ratio, 0.42; 95% confidence interval, 0.18-0.94). There were no treatment differences in the incidence of adverse events, including gastrointestinal upset (56% vs 61% for cranberry vs placebo).
CONCLUSION: Among women undergoing elective benign gynecological surgery involving urinary catheterization, the use of cranberry extract capsules during the postoperative period reduced the rate of UTI by half.

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: Cranberry extracts have been tested as a nutritional supplementation in the prevention of recurrent lower-urinary tract infections (R-UTIs), with mixed results. This pilot, registry study evaluates the prophylactic effects of oral supplementation with a new well-standardized cranberry extract in patients with R-UTI, over a 2-month follow-up.
PATIENTS AND METHODS: All subjects were suggested to take one capsule containing a cranberry extract (AnthocranTM) for 60 days and were also given lifestyle advice. Clinical outcomes were compared between patients on cranberry extracts and those who don't take this supplementation.
RESULTS: In total, 22 subjects completed the study in each of the two groups. In the cranberry group, the reduction in the frequency of UTI episodes during the study period compared with the two months before the inclusion was 73.3% (p 0.05). This figure was 15.4% in the control group (p 0.05; p = 0.012 vs cranberry group). Seven (31.8%) subjects in the cranberry group were symptom-free; no patient was symptom-free in the control group (p 0.05). The mean duration of UTI episodes was 2.5 +/- 1.3 days in the cranberry group, compared with 3.6 +/- 1.7 days in subjects not on cranberry (p 0.05). Three subjects (13.6%) in the cranberry group and 8 (36.3%) in the control group required medical consultation for UTI symptoms (p 0.05). Urine evaluation was completely negative in 20/22 subjects in the Cranberry group (90.9%) and in 11 control subjects (50.0%; p 0.005). No adverse events were observed.
CONCLUSIONS: These preliminary results, obtained in a field-practice setting, indicates the effectiveness and safety of a well-standardized cranberry extract in the prevention of R-UTI.

Cranberry juice has been recognized as a treatment for urinary tract infections on the basis of scientific reports of proanthocyanidin anti-adhesion activity against Escherichia coli as well as from folklore. Xyloglucan oligosaccharides were detected in cranberry juice and the residue remaining following commercial juice extraction that included pectinase maceration of the pulp. A novel xyloglucan was detected through tandem mass spectrometry analysis of an ion at m/z 1055 that was determined to be a branched, three hexose, four pentose oligosaccharide consistent with an arabino-xyloglucan structure. Two-dimensional nuclear magnetic resonance spectroscopy analysis provided through-bond correlations for the alpha-l-Araf (1->2) alpha-d-Xylp (1->6) beta-d-Glcp sequence, proving the S-type cranberry xyloglucan structure. Cranberry xyloglucan-rich fractions inhibited the adhesion of E. coli CFT073 and UTI89 strains to T24 human bladder epithelial cells and that of E. coli O157:H7 to HT29 human colonic epithelial cells. SSGG xyloglucan oligosaccharides represent a new cranberry bioactive component with E. coli anti-adhesion activity and high affinity for type 1 fimbriae.

Procyanidins in cranberries are predominantly polymers (>85%). The objective of this study was to optimise the depolymerisation of polymers and to investigate the absorption of resultant oligomers on Caco-2 cell monolayers. Depolymerisation conditions were optimised using response surface methodology. Depolymerisation, with or without added epicatechin, yielded 644 mug and 202 mug of oligomers (monomer through tetramers) per mg of partially purified polymers (PP), respectively. Oligomers (yielded from both methods) were transported through Caco-2 cell monolayer despite absorption rates being low. With the aid of response surface methodology, the optimum depolymerisation conditions were determined to be 60degreeC, 0.1M HCl in methanol and 3h without added epicatechin. The predicted maximum yield was 364 mug oligomers per mg of PP. The optimum depolymerisation condition with added epicatechin shared the same temperature, acid concentration and reaction time, in addition to an epicatechin/PP mass ratio of 2.19. Its predicted maximum oligomer yield was 1,089 mug/mg. The predicted yields were verified by experimental data.

BACKGROUND: Previous investigations showed that a high-molecular-weight, nondialyzable material (NDM) from cranberries inhibits the adhesion of a number of bacterial species and prevents the coaggregation of many oral bacterial pairs.
AIM: In the present study, the effect of mouthrinse containing high-molecular-weight component of cranberry was evaluated on colonization of Streptococcus mutans in children and compared it with a control mouthrinse without high-molecular-weight component on Streptococcus mutans counts.
MATERIALS AND METHODS: A high-molecular-weight NDM was isolated from cranberry juice concentrate after the dialysis of the cranberry concentrate; followed by lyophilization. A mouthwash was prepared especially for the study having NDM in the concentration of 3 mg/ml. Following 4 weeks of daily usage of cranberry-containing mouthwash by the children of an experimental group (n = 20), the Streptococcus mutans counts in plaque and saliva were compared with that in control group using placebo mouthwash (n = 20) with the help of Dentocult SM strips.
RESULTS: There was a highlysignificant reduction in Streptococcus mutans counts in saliva and plaque of children using mouthwash containing cranberry NDM (P 0.05) compared to control.
CONCLUSION: The data suggest that the high-molecular-weight cranberry extract in mouthwash has a significant potential in reducing the Streptococcus counts in the oral environment.

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.

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.