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Anti-Adhesive Activity of Cranberry Phenolic Compounds and Their Microbial-Derived Metabolites against Uropathogenic Escherichia coli in Bladder Epithelial Cell Cultures

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Authors
de Llano DG, Esteban-Fernandez A, Sanchez-Patan F, Martinlvarez PJ, Moreno-Arribas MV, Bartolome B
Journal
Int J Mol Sci 16(6):12119-30
Abstract

Cranberry consumption has shown prophylactic effects against urinary tract infections (UTI), although the mechanisms involved are not completely understood. In this paper, cranberry phenolic compounds and their potential microbial-derived metabolites (such as simple phenols and benzoic, phenylacetic and phenylpropionic acids) were tested for their capacity to inhibit the adherence of uropathogenic Escherichia coli (UPEC) ATCC53503TM to T24 epithelial bladder cells. Catechol, benzoic acid, vanillic acid, phenylacetic acid and 3,4-dihydroxyphenylacetic acid showed anti-adhesive activity against UPEC in a concentration-dependent manner from 100-500 micro M, whereas procyanidin A2, widely reported as an inhibitor of UPEC adherence on uroepithelium, was only statistically significant (p < 0.05) at 500 micro M (51.3% inhibition). The results proved for the first time the anti-adhesive activity of some cranberry-derived phenolic metabolites against UPEC in vitro, suggesting that their presence in the urine could reduce bacterial colonization and progression of UTI.

Antibiotic susceptibility of urinary isolates in nursing home residents consuming cranberry capsules versus placebo

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Authors
Madden GR, Argraves SM, Van Ness PH, Juthani-Mehta M
Journal
Infect Control Hosp Epidemiol 36(3):356-7
Abstract

Urinary tract infection (UTI) is the most common infection
among nursing home residents, and the microorganisms pre-valent in this setting pose significant challenges for treatment. Cranberries (Vaccinium macrocarpon Aiton
) are thought to reduce UTIs; this view is supported by a placebo-controlled trial showing lower rates of bacteriuria plus pyuria with daily ingestion of 300 mL of cranberry juice cocktail (15.0% versus 28.1% in controls). However, subsequent studies of cranberries for prevention of UTI, including a large Cochrane meta-analysis, have shown mixed results. Various mechanisms of the bacteriologic effect of cranberries are postulated; however, inhibition of P fimbriae–mediated adhesion of E. coli by proanthocyanidin (PAC) remains the leading theory.
We sought to compare antibiotic susceptibility and proportions of non–E. coli Enterobacteriaceae among Gram-negative urinary isolates from participants randomized to cranberry capsules compared to placebo.

Characterization and comparison of phenolic composition, antioxidant capacity and instrumental taste profile of juices from different botanical origins

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Authors
Granato D, Karnopp AR, van Ruth SM
Journal
J Sci Food Agric 95(10):1997-2006
Abstract

BACKGROUND: The European Union registered a consumption of about 10.7 billion litres of juices in 2011 and a great part of this amount is imported from other countries, which makes the monitoring of their quality essential. This work was aimed at mapping the quality of various juices from different botanical origins from instrumental taste, chemical marker and antioxidant capacity perspectives. It also characterized the individual phenolic composition of juices previously classified according to their antioxidant activity and total phenolic material level.
RESULTS: Overall, by using correlation analysis and chemometrics (HCA and PCA), data showed that total phenolics, specifically gallic acid, p-coumaric acid, anthocyanins, flavanols and flavonols, are the main contributors to the antioxidant activity. Elderberry and pomegranate juices presented the highest phenolic content and antioxidant activity. On the other hand, orange, apple and cranberry juices had the lowest levels of total phenolics and flavonoids, DPPH and CUPRAC.
CONCLUSION: The use of chemometrics coupled to ANOVA seems to be a suitable approach to evaluate the quality of fruit juices from different botanical origins. Additionally, the instrumental taste profile correlated well with the chemical composition and antioxidant capacity, showing its potential application in assessing the functionality of juices.

Chemical characterization and chemo-protective activity of cranberry phenolic powders in a model cell culture. Response of the antioxidant defenses and regulation of signaling pathways

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Journal
Food Res Int 71:68-82
Abstract

Oxidative stress and reactive oxygen species (ROS)-mediated cell damage are implicated in various chronic pathologies. Emerging studies show that polyphenols may act by increasing endogenous antioxidant defense potential. Cranberry has one of the highest polyphenol content among commonly consumed fruits. In this study, the hepato-protective activity of a cranberry juice (CJ) and cranberry extract (CE) powders against oxidative stress was screened using HepG2 cells, looking at ROS production, intracellular non-enzymatic and enzymatic antioxidant defenses by reduced glutathione concentration (GSH), glutathione peroxidase (GPx) and glutathione reductase (GR) activity and lipid peroxidation biomarker malondialdehyde (MDA). Involvement of major protein kinase signaling pathways was also evaluated. Both powders in basal conditions did not affect cell viability but decreased ROS production and increased GPx activity, conditions that may place the cells in favorable conditions against oxidative stress. Powder pre-treatment of HepG2 cells for 20 h significantly reduced cell damage induced by 400 micro M tert-butylhydroperoxide (t-BOOH) for 2 h. Both powders (5-50 micro g/ml) reduced t-BOOH-induced increase of MDA by 20% (CJ) and 25% (CE), and significantly reduced over-activated GPx and GR. CE, with a significantly higher amount of polyphenols than CJ, prevented a reduction in GSH and significantly reduced ROS production. CJ reversed the t-BOOH-induced increase in phospho-c-Jun N-terminal kinase. This study demonstrates that cranberry polyphenols may help protect liver cells against oxidative insult by modulating GSH concentration, ROS and MDA generation, antioxidant enzyme activity and cell signaling pathways.

Comparative assessment of Cranberry and Chlorhexidine mouthwash on streptococcal colonization among dental students: A randomized parallel clinical trial.

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Authors
Khairnar MR, Karibasappa GN, Dodamani AS, Vishwakarma P, Naik RG, Deshmukh MA
Journal
Contemp Clin Dent 6(1):35-9
Abstract

BACKGROUND: Chlorhexidine gluconate mouthwash has earned an eponym of the gold standard against oral infections, but with certain limitations. There is no effective alternative to Chlorhexidine. Cranberry is known to inhibit bacterial adhesion in various systemic infections and acts as a strong antioxidant. However, it is less explored for its dental use. Hence, there is a need to evaluate its effect against oral infections.
AIM: The aim was to compare the efficacy of 0.2% Chlorhexidine mouthwash with 0.6% Cranberry mouthwash on Streptococcus mutans.
MATERIALS AND METHODS: This was a double-blind, randomized parallel group clinical trial. Total sample of 50 subjects, aged 18-20 years, were randomly divided into two groups, Group A (25) and Group B (25) were given 10 mL of Chlorhexidine mouthwash and Cranberry mouthwash twice daily, respectively, for 14 days each. The plaque samples, which were taken from the subjects on 1(st) day and 14(th) day, were inoculated on blood agar plates and incubated at 37degreeC for 24-48 h. Number of streptococcal colony forming units were calculated using digital colony counter. The data were subjected to paired t-test and unpaired t-test at a 5% significance level.
RESULTS: (1) Chlorhexidine mouthwash showed 69% reduction whereas Cranberry mouthwash showed 68% reduction in S. mutans count. (2) No significant difference was seen between Chlorhexidine and Cranberry mouthwash on streptococci.
CONCLUSION: Cranberry mouthwash is equally effective as Chlorhexidine mouthwash with beneficial local and systemic effect. Hence, it can be used effectively as an alternative to Chlorhexidine mouthwash.

Comparative in vitro fermentations of cranberry and grape seed polyphenols with colonic microbiota.

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Authors
Sanchez-Patan F, Barroso E, van de Wiele T, Jimenez-Giron A, Martin-Alvarez PJ, Moreno-Arribas MV, Martinez-Cuesta MC, Pelaez C, Requena T, Bartolome B
Journal
Food Chem 183:273-82,
Abstract

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.

Cranberries (Oxycoccus quadripetalus) inhibit lipid metabolism and modulate leptin and adiponectin secretion in 3T3-L1 adipocytes

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Authors
Kowalska K, Olejnik A, Rychlik J, Grajek W
Journal
Food Chem 185:383-8
Abstract

It has previously been shown that lyophilized cranberries (LCB) decreased lipid accumulation in 3T3-L1 cells and inhibited preadipocyte differentiation by down-regulation of the expression of key transcription factors (PPARgamma, C/EBPalpha, SREBP1) of the adipogenesis pathway. To elucidate the molecular basis of anti-lipogenic activity of LCB, the expression of several genes involved in lipid metabolism, such as adipocyte fatty acid-binding protein (aP2), lipoprotein lipase (LPL), fatty acid synthase (FAS), hormone sensitive lipase (HSL) and perilipin 1 (PLIN1), was examined in the present study. Additionally, the effects of LCB on adiponectin and leptin expression and protein secretion were also investigated. LCB reduced lipid accumulation during preadipocyte differentiation by down-regulation of the mRNA level of aP2, FAS, LPL, HSL and PLIN1. Moreover, LCB decreased leptin gene expression and increased adiponectin gene expression and protein secretion in a dose-dependent manner. Therefore cranberries could be considered as bioactive factors, which are effective in the inhibition of adipose tissue mass production.

Cranberry flavonoids prevent toxic rat liver mitochondrial damage in vivo and scavenge free radicals in vitro.

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Authors
Lapshina EA, Zamaraeva M, Cheshchevik VT, Olchowik-Grabarek E, Sekowski S, Zukowska I, Golovach NG, Burd VN, Zavodnik IB
Journal
Cell Biochem Funct 33(4):202-10
Abstract

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.

Cranberry fruit powder (Flowens™)improves lower urinary tract symptoms in men: a double-blind, randomized, placebo-controlled trial

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Authors
Vidlar A, Student Jr V, Vostalova J, Fromentin E, Roller M, Simanek V, Student V
Journal
World J Urol DOI 10.1007/s00345-015-1611-7
Abstract

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.

Cranberry juice capsules and urinary tract infection after surgery: results of a randomized trial

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Authors
Foxman B, Cronenwett AE, Spino C, Berger MB, Morgan DM
Journal
Am J Obstet Gynecol 213(2):194.e1-8
Abstract

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.