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5-(3',4'-dihydroxyphenyl)- Gamma -Valerolactone and its Sulphate Conjugates, Representative Circulating Metabolites of Flavan-3-ols, Exhibit Anti-Adhesive Activity Against Uropathogenic Escherichia Coli in Bladder Epithelial Cells.

Posted: August 15, 2017
Authors: Mena, P. Llano, D. G. de Brindani, N. Esteban-Fernandez, A. Curti, C. Moreno-Arribas, M. V. Rio, D. del Bartolome, B.
Journal: Journal of Functional Foods 29:275-280

Abstract: Urinary tract infections (UTI) are mostly caused by uropathogenic Escherichia coli (UPEC). Cranberry-based products have shown preventive effects against UTI, and this has been partially attributed to their A-type proanthocyanidin content. However, recent evidence reports phenyl- gamma -valerolactones as the most relevant urinary metabolites of cranberry procyanidins, and candidates these compounds as plausible responsible for the protective effects of cranberries against UTI. This paper studied the inhibition of the adherence of UPEC ATCCReg. 53503TM to T24 bladder epithelial cells by physiological concentrations of differently sulphated dihydroxyphenyl- gamma -valerolactones. Moreover, the transformations of these molecules in the cell media were evaluated by UHPLC-MSn. All dihydroxyphenyl- gamma -valerolactone derivatives showed anti-adhesive activity at 100 micro M, while 5-(3'-hydroxyphenyl)- gamma -valerolactone-4-O-sulphate also showed neuro-protective effects at 50 micro M. Some compounds underwent extensive metabolism during cell incubation, mainly deconjugation of sulphate moieties and opening of the lactone ring. These results shed light on the flavan-3-ol metabolites behind the prophylactic effect of cranberries against UTI.

A Human Gut Commensal Ferments Cranberry Carbohydrates to Produce Formate.

Posted: August 15, 2017
Authors: Ozcan E; Sun J; Rowley DC; Sela DA.
Journal: Applied & Environmental Microbiology 10.1128/AEM.01097-17 [doi]

Abstract: Commensal bifidobacteria colonize the human gastrointestinal tract and catabolize glycans that are impervious to host digestion. Accordingly, Bifidobacterium longum typically secrete acetate and lactate as fermentative endproducts. This study tested the hypothesis that B. longum utilize cranberry-derived xyloglucans in a strain-dependent manner. Interestingly, the B. longum strain that efficiently utilizes cranberry xyloglucans secrete 2.0-2.5 moles acetate:lactate. The 1.5 ratio theoretical yield obtained in hexose fermentations shifts during xyloglucan metabolism. Accordingly, this metabolic shift is characterized by increased acetate and formate production at the expense of lactate. alpha-L-arabinofuranosidase, an arabinan endo-1,5-alpha-L-arabinosidase, and a beta-xylosidase with a carbohydrate substrate-binding protein and carbohydrate ABC transporter membrane proteins are upregulated (> 2-fold change), which suggests carbon flux through this catabolic pathway. Finally, syntrophic interactions occurred with strains that utilize carbohydrate products derived from initial degradation from a heterologous bacterium.IMPORTANCE This is a study of bacterial metabolism of complex cranberry carbohydrates termed xyloglucans that are likely not digested prior to reaching the colon. This is significant as bifidobacteria interact with this dietary compound to potentially impact human host health through energy and metabolite production by bacterial utilization of these substrates. Specific bacterial strains utilize cranberry xyloglucans as a nutritive source indicating unknown mechanisms that are not universal in bifidobacteria. In addition, xyloglucan metabolism proceeds using an alternative pathway could lead to further research to investigate mechanisms underlying this interaction. Finally, we observed cross-feeding between bacteria in which one strain degrades the cranberry xyloglucan to make it available to a second strain. Similar nutritive strategies are known to occur within the gut. In aggregate, this study may lead to novel foods or supplements to impact human health through rational manipulations of their microbiome.

Absorption, Metabolism and Excretion of Cranberry (Poly)Phenols in Humans: a Dose Response Study and Assessment of Inter-Individual Variability

Posted: August 15, 2017
Authors: Feliciano, R. P. Mills, C. E. Istas, G. Heiss, C. Rodriguez-Mateos, A.
Journal: Nutrients 9(3):268

Abstract: The beneficial health effects of cranberries have been attributed to their (poly)phenol content. Recent studies have investigated the absorption, metabolism and excretion of cranberry (poly)phenols; however, little is known about whether they follow a dose response in vivo at different levels of intake. An acute double-blind randomized controlled trial in 10 healthy men with cranberry juices containing 409, 787, 1238, 1534 and 1910 mg total (poly)phenols was performed. Blood and urine were analyzed by UPLC-Q-TOF-MS. Sixty metabolites were identified in plasma and urine including cinnamic acids, dihydrocinnamic, flavonols, benzoic acids, phenylacetic acids, benzaldehydes, valerolactones, hippuric acids, catechols, and pyrogallols. Total plasma, but not excreted urinary (poly)phenol metabolites, exhibited a linear dose response (r2=0.74, p<0.05), driven by caffeic acid 4-O- beta -D-glucuronide, quercetin-3-O- beta -D-glucuronide, ferulic acid 4-O- beta -D-glucuronide, 2,5-dihydroxybenzoic acid, 2,4-dihydroxybenzoic acid, ferulic acid, caffeic acid 3-O- beta -D-glucuronide, sinapic acid, ferulic acid 4-O-sulfate, 3-hydroxybenzoic acid, syringic acid, vanillic acid-4-O-sulfate, (4R)-5-(3'-hydroxyphenyl)- gamma -valerolactone-4'-O-sulfate, 4-methylgallic acid-3-O-sulfate, and isoferulic acid 3-O-sulfate (all r2 >=0.89, p<0.05). Inter-individual variability of the plasma metabolite concentration was broad and dependent on the metabolite. Herein, we show that specific plasma (poly)phenol metabolites are linearly related to the amount of (poly)phenols consumed in cranberry juice. The large inter-individual variation in metabolite profile may be due to variations in the gut microbiome.

Anti-Aging and Redox State Regulation Effects of A-type Proanthocyanidins-Rich Cranberry Concentrate and its Comparison with Grape Seed Extract in Mice.

Posted: August 15, 2017
Authors: Jiao JJ, Wei Y, Chen J, Chen X, Zhang Y.
Journal: Journal of Functional Foods 30:63-73

Abstract: We investigated the anti-aging and redox state regulation effects by A-type proanthocyanidins (PACs)-rich cranberry concentrate (CBC) and its comparison with B-type PACs-rich grape seed extract (GSE). Using the Q-Extractive mass spectrometry, PACs dimer A and B were identified as predominant phenolic compounds of CBC and GSE, respectively, while epicatechin was present in both extracts. Using the d-galactose-induced aging mice model, effects were investigated via an 8-week oral gavage considering water-soluble vitamin E as the positive control. Both CBC and GSE reduced hepatic and brain thiobarbituric acid reactive substances, and plasma 8-isoprostane levels by 30-57%, 24-30% and 11-62%, respectively, and decreased brain and plasma monoamine oxidase activities by 27-59% and 65-71%, respectively. CBC could improve hepatic glutathione peroxidase activity by 42%, while GSE increased hepatic superoxide dismutase activity by 13%. Therefore, both extracts exerted anti-aging effects probably via regulating in vivo redox state. However, neither generated any effect on catalase activities.

Antiadhesive Activity and Metabolomics Analysis of Rat Urine after Cranberry (Vaccinium macrocarpon Aiton) Administration.

Posted: August 15, 2017
Authors: Peron G, Pellizzaro A, Brun P, Schievano E, Mammi S, Sut S, Castagliuolo I, Dall'Acqua S
Journal: J Agric Food Chem. 65(28):5657-5667

Abstract: Cranberry (Vaccinium macrocarpon Aiton) is used to treat noncomplicated urinary tract infections (UTIs). A-type procyanidins (PAC-A) are considered the active constituents able to inhibit bacterial adhesion to the urinary epithelium. However, the role of PAC-A in UTIs is debated, because of their poor bioavailability, extensive metabolism, limited knowledge about urinary excretion, and contradictory clinical trials. The effects of 35-day cranberry supplementation (11 mg/kg PAC-A, 4 mg/kg PAC-B) were studied in healthy rats using a ultra performance liquid chromatography-mass spectrometry (UPLC-MS)-based metabolomics approach. Microbial PAC metabolites, such as valeric acid and valerolactone derivatives, were related to cranberry consumption. An increased urinary excretion of glucuronidated metabolites was also observed. In a further experiment, urine samples were collected at 2, 4, 8, and 24 h after cranberry intake and their antiadhesive properties were tested against uropathogenic Escherichia coli. The 8 h samples showed the highest activity. Changes in urinary composition were studied by ultra performance liquid chromatography-time-of-flight (UPLC-QTOF), observing the presence of PAC metabolites. The PAC-A2 levels were measured in all collected samples, and the highest amounts, on the order of ng/mL, were found in the samples collected after 4 h. Results indicate that the antiadhesive activity against uropathogenic bacteria observed after cranberry consumption is ascribable to PAC-A metabolites rather than to a direct PAC-A effect, as the measured PAC-A levels in urine was lower than those reported as active in the literature.

Can Cranberries Contribute to Reduce the Incidence of Urinary Tract Infections? A Systematic Review with Meta-Analysis and Trial Sequential Analysis of Clinical Trials.

Posted: August 15, 2017
Authors: Luis A; Domingues F; Pereira L.
Journal: Journal of Urology https://doi.org/10.1016/j.juro.2017.03.078

Abstract: PURPOSE: We sought to clarify the association between cranberry intake and the prevention of urinary tract infections. MATERIALS AND METHODS: This systematic review, which complies with the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis) statement, was done as a meta-analysis and trial sequential analysis of clinical trials. RESULTS: The findings clearly showed the potential use of cranberries for the clinical condition of urinary tract infection. Cranberry products significantly reduced the incidence of urinary tract infections as indicated by the weighted risk ratio (0.6750, 95% CI 0.5516-0.7965, p <0.0001). The results of subgroup analysis demonstrated that patients at some risk for urinary tract infections were more susceptible to the effects of cranberry ingestion. CONCLUSIONS: The results of the current study could be used by physicians to recommend cranberry ingestion to decrease the incidence of urinary tract infections, particularly in individuals with recurrent urinary tract infections. This would also reduce the administration of antibiotics, which could be beneficial since antibiotics can lead to the worldwide emergence of antibiotic resistant microorganisms.

Characterization of Non-Dialyzable Constituents from Cranberry Juice that Inhibit Adhesion, Co-Aggregation and Biofilm Formation by Oral Bacteria

Posted: August 15, 2017
Authors: Neto CC; Penndorf KA; Feldman M; Meron-Sudai S; Zakay-Rones Z; Steinberg D; Fridman M; Kashman Y; Ginsburg I; Ofek I; Weiss EI.
Journal: Food & Function. 8(5):1955-1965

Abstract: An extract prepared from cranberry juice by dialysis known as nondialyzable material (NDM) has been shown previously to possess anti-adhesion activity toward microbial species including oral bacteria, uropathogenic Escherichia coli and Helicobacter pylori. Bioassay-guided fractionation of cranberry NDM was therefore undertaken to identify the anti-adhesive constituents. An aqueous acetone-soluble fraction (NDMac) obtained from Sephadex LH-20 inhibited adhesion-linked activities by oral bacteria, including co-aggregation of oral bacteria Fusobacterium nucleatum with Streptococcus sanguinis or Porphyromonas gingivalis, and biofilm formation by Streptococcus mutans. Analysis of NDMac and subsequent subfractions by MALDI-TOF MS and 1H NMR revealed the presence of A-type proanthocyanidin oligomers (PACs) of 3-6 degrees of polymerization composed of (epi)catechin units, with some (epi)gallocatechin and anthocyanin units also present, as well as quercetin derivatives. Subfractions containing putative xyloglucans in addition to the mixed polyphenols also inhibit biofilm formation by S. mutans (MIC = 125-250 mug mL-1). These studies suggest that the anti-adhesion activities of cranberry NDM on oral bacteria may arise from a combination of mixed polyphenol and non-polyphenol constituents.

Comparative Evaluation of Anti-Microbial Efficacy of Cranberry Extract and Chlorhexidine Mouthwash on Periodontal Pathogens: An In-vitro Study

Posted: August 15, 2017
Authors: Dandekar S, Deshpande N, Dave D
Journal: J. Periodont. Pract. DOI: http://dx.doi.org/10.20936/jpp/170102

Abstract: BACKGROUND: Chlorhexidine gluconate is considered as the gold standard among various anti-plaque agents. However, many local side effects have been reported on its long term use. Cranberry (Vaccinium macrocarpon) is rich in polyphenols, including flavonoids and proanthrocyanidins. Insufficient evidences are available to support antimicrobial property of Cranberry extract mouthwash in context to red, orange and green complexes of periodontal pathogens and even comparison of same with clinically used and accepted 0.2% Chlorhexidine. MATERIALS AND METHODS: Sterilised nutrient agar plates were inoculated with suspensions of P. gingivalis, T. forsythia, P. intermedia and A. actinomycetemcomitans (overnight cultures grown at 37° on nutrient agar). The strains were allowed to grow in strict anaerobic condition. 1, 5, 10 and 15 mg/ml Cranberry extract, 0.2% Chlorhexidine and distilled water were added into wells. Plates were then again incubated at 37° for 24 hours. Diameter of zones of inhibition of all the plates was measured using digital vernier callipers. The mean score of zones of inhibition was calculated. RESULTS: Results of the study showed that all four concentrations of Cranberry extract showed comparatively less significant antimicrobial property against the microorganisms, compared to 0.2% Chlorhexidine. CONCLUSION: This study showed that 1, 5, 10 and 15 mg/ml Cranberry extract does not have significant antimicrobial efficacy against periodontopathogens, compared to that of 0.2% Chlorhexidine.

Cranberries Improve Postprandial Glucose Excursions in type 2 Diabetes

Posted: August 15, 2017
Authors: Schell J; Betts NM; Foster M; Scofield RH; Basu A.
Journal: Food & Function, DOI:10.1039/C7FO00900C

Abstract: Recent research supports a favorable role of cranberries on cardiometabolic health. Postprandial metabolism, especially hyperglycemia, has been shown to be an independent cardiovascular risk and few clinical studies have reported the role of berries in improving postprandial dysmetabolism. We investigated the postprandial effects of dried cranberries following a high-fat breakfast challenge in obese participants with type 2 diabetes (T2DM), in a randomized crossover trial. Blood draw and vascular measurements were conducted at fasting, 1, 2 and 4 hours (h), following the consumption of a fast-food style high-fat breakfast (70 g fat, 974 kcal) with or without cranberries (40 g). Analyses of our data (n = 25; BMI (kg m-2) (mean +/- s.d.) = 39.5 +/- 6.5; age (years) = 56 +/- 6) revealed that postprandial increases in glucose were significantly lower in the cranberry vs. control at 2 & 4 h (p < 0.05). No significant differences were noted in insulin, insulin resistance evaluated by homeostasis model assessment, lipid profiles and blood pressure between the cranberry and control groups. Among the biomarkers of inflammation and oxidation, postprandial serum interleukin-18 and malondialdehyde were significantly lower at 4 h, and serum total nitrite was higher at 2 h in the cranberry vs. control group (all p < 0.05). No effects were noted on C-reactive protein or interlukin-6. Overall, dietary cranberries had notable effects in improving high-fat breakfast induced postprandial glucose and selected biomarkers of inflammation and oxidation in participants with T2DM. These findings provide evidence that adding whole cranberries to a high-fat meal may improve postprandial blood glucose management and warrant further investigation.

Cranberry (Vaccinium macrocarpon ) Proanthocyanadin Complexes with Proteins Modulate the Macrophage Activation

Posted: August 15, 2017
Authors: Carballo S, Haas L, Krueger C, Reed JD
Journal: Food Funct DOI:10.1039/C7FO00688H

Abstract: In this work we characterize the interaction of cranberry (Vaccinium macrocarpon) proanthocyanidins (PAC) with bovine serum albumin (BSA) and hen egg-white lysozyme (HEL) and determine the effects of these complexes on macrophage activation and antigen presentation. We isolated PAC from cranberry and complexed the isolated PAC with BSA and HEL. The properties of the PAC-protein complexes were studied by matrix assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS), gel electrophoresis and zeta-potential. The effects of PAC-BSA complexes on macrophage activation were studied in RAW 264.7 macrophage like cells after treatment with lipopolysaccharide (LPS). Fluorescent microscopy was used to study endocytosis of PAC-BSA complexes. The effects of PAC complexes on macrophage antigen presentation was studied in an in vitro model of HEL antigen presentation by mouse peritoneal mononuclear cells to a T-cell hybridoma. Mass spectra of PAC complexes with BSA and HEL differed from spectra of the proteins alone by the presence of broad shoulders on the singly and doubly charged protein peaks. Complexation with PAC altered the electrophoretic mobility shift assay in native agarose gel and the electrophoretic mobility (&#950;-potential) values. These results indicate that the PAC-protein complexes are stable and alter protein structure without precipitating the protein. Fluorescent microscopy showed that RAW 264.7 macrophages endocytosed BSA and PAC-BSA complexes in discrete vesicles that surrounded the nucleus. Macrophages treated with increasing amounts of PAC-BSA complexes had significantly reduced COX-2 and iNOS expression in response to treatment with lipopolysaccharide (LPS) in comparison to controls. PAC-HEL complexes modulated antigen uptake, processing and presentation in murine peritoneal macrophages. After 4 h of pre-incubation, only trace amounts of IL-2 were detected in the co-cultures treated with HEL alone, whereas a PAC-HEL complex had already reached maximum IL-2 expression. Cranberry PAC may increase rate of endocytose of HEL and subsequent expression of IL-2 by the T-cell hybridomas. These results suggest that PAC-protein complexes modulate aspects of innate and acquired immune responses in macrophages.

Cranberry (Vaccinium macrocarpon) Extract Treatment Improves Triglyceridemia, Liver Cholesterol, Liver Steatosis, Oxidative Damage and Corticosteronemia in Rats Rendered Obese by High Fat Diet.

Posted: August 15, 2017
Authors: Peixoto TC; Moura EG; de Oliveira E; Soares PN; Guarda DS; Bernardino DN; Ai XX; Rodrigues VDST; de Souza GR; da Silva AJR; Figueiredo MS; Manhaes AC; Lisboa PC.
Journal: European Journal of Nutrition DOI 10.1007/s00394-017-1467-2

Abstract: PURPOSE: Obese individuals have higher production of reactive oxygen species, which leads to oxidative damage. We hypothesize that cranberry extract (CE) can improve this dysfunction in HFD-induced obesity in rats since it has an important antioxidant activity. Here, we evaluated the effects of CE in food intake, adiposity, biochemical and hormonal parameters, lipogenic and adipogenic factors, hepatic morphology and oxidative balance in a HFD model. METHODS: At postnatal day 120 (PN120), male Wistar rats were assigned into two groups: (1) SD (n = 36) fed with a standard diet and (2) HFD (n = 36), fed with a diet containing 44.5% (35.2% from lard) energy from fat. At PN150, 12 animals from SD and HFD groups were killed while the others were subdivided into four groups (n = 12/group): animals that received 200 mg/kg cranberry extract (SD CE, HFD CE) gavage/daily/30 days or water (SD, HFD). At PN180, animals were killed.RESULTS: HFD group showed higher body mass and visceral fat, hypercorticosteronemia, higher liver glucocorticoid sensitivity, cholesterol and triglyceride contents and microsteatosis. Also, HFD group had higher lipid peroxidation (plasma and tissues) and higher protein carbonylation (liver and adipose tissue) compared to SD group. HFD CE group showed lower body mass gain, hypotrygliceridemia, hypocorticosteronemia, and lower hepatic cholesterol and fatty acid synthase contents. HFD CE group displayed lower lipid peroxidation, protein carbonylation (liver and adipose tissue) and accumulation of liver fat compared to HFD group. CONCLUSION: Although adiposity was not completely reversed, cranberry extract improved the metabolic profile and reduced oxidative damage and steatosis in HFD-fed rats, which suggests that it can help manage obesity-related disorders.

Cranberry capsules to prevent nosocomial urinary tract bacteriuria after pelvic surgery: a randomised controlled trial.

Posted: August 15, 2017
Authors: Letouzey V; Ulrich D; Demattei C; Alonso S; Huberlant S; Lavigne JP; de Tayrac R.
Journal: BJOG: An International Journal of Obstetrics & Gynaecology. 124(6):912-917

Abstract: OBJECTIVE: To evaluate whether cranberries are able to prevent postoperative urinary bacteriuria in patients undergoing pelvic surgery and receiving transurethral catheterisation.DESIGN: Randomised, double-blind, placebo-controlled trial.SETTINGS: French tertiary Care centre, University Hospital.POPULATION: A total of 272 women undergoing pelvic surgery aged 18 or older.METHODS: Participants undergoing pelvic surgery were randomised to 36 mg cranberry (proanthocyanidins, PAC) or placebo once daily for 10 days. Statistical analysis was performed by a chi-square test.MAIN OUTCOME MEASURES: The primary and secondary outcomes were postoperative bacteriuria, defined by a positive urine culture, within the first 15 and 40 days, respectively.RESULTS: Two hundred and fifty-five participants received the intended treatment: 132 (51.8%) received PAC and 123 (48.2%) received placebo. There were no significant differences in baseline demographics, intra-operative characteristics or duration and type of catheterisation between the two groups. PAC prophylaxis did not reduce the risk of bacteriuria treatment within 15 days of surgery [27% bacteriuria with PAC compared with 25% bacteriuria with placebo: relative risk 1.05, 95% CI 0.78-1.4, P = 0.763). The same result was observed on day 40. Bacteriuria occurred more often in older women with increased length of catheterisation.CONCLUSION: Immediate postoperative prophylaxis with PAC does not reduce the risk of postoperative bacteriuria in patients receiving short-term transurethral catheterisation after pelvic surgery.

Cranberry Extract Inhibits in Vitro Adhesion of F4 and F18+ Escherichia Coli to Pig Intestinal Epithelium and Reduces in Vivo Excretion of Pigs Orally Challenged with F18+ Verotoxigenic E. Coli.

Posted: August 15, 2017
Authors: Coddens, A. Loos, M. Vanrompay, D. Remon, J. P. Cox, E.
Journal: Veterinary Microbiology 202:64-71

Abstract: F4+ E. coli and F18+ E. coli infections are an important threat for pig industry worldwide. Antibiotics are commonly used to treat infected piglets, but the emerging development of resistance against antibiotics raises major concerns. Hence, alternative therapies to prevent pigs from F4+ E. coli and F18+ E. coli infections need to be developed. Since cranberry previously showed anti-adhesive activity against uropathogenic E. coli, we aimed to investigate whether cranberry extract could also inhibit binding of F4+ E. coli and F18+ E. coli to pig intestinal epithelium. Using the in vitro villus adhesion assay, we found that low concentrations of cranberry extract (20 micro g or 100 micro g/ml) have strong inhibitory activity on F4+ E. coli (75.3%, S.D.=9.31 or 95.8%, S.D.=2.56, respectively) and F18+ E. coli adherence (100% inhibition). This effect was not due to antimicrobial activity. Moreover, cranberry extract (10 mg or 100 mg) could also abolish in vivo binding of F4 and F18 fimbriae to the pig intestinal epithelium in ligated loop experiments. Finally, two challenge experiments with F18+ E. coli were performed to address the efficacy of in-feed or water supplemented cranberry extract. No effect could be observed in piglets that received cranberry extract only in feed (1 g/kg or 10 g/kg). However, supplementation of feed (10 g/kg) and drinking water (1 g/L) significantly decreased excretion and diarrhea. The decreased infection resulted in a decreased serum antibody response indicating reduced exposure to F18+ E. coli.

Cranberry Juice and Combinations of Its Organic Acids Are Effective against Experimental Urinary Tract Infection.

Posted: August 15, 2017
Authors: Jensen HD; Struve C; Christensen SB; Krogfelt KA.
Journal: Frontiers in Microbiology. 8:542

Abstract: The antibacterial effect of cranberry juice and the organic acids therein on infection by uropathogenic Escherichia coli was studied in an experimental mouse model of urinary tract infection (UTI). Reduced bacterial counts were found in the bladder (P < 0.01) of mice drinking fresh cranberry juice. Commercially available cranberry juice cocktail also significantly reduced (P < 0.01) bacterial populations in the bladder, as did the hydrophilic fraction of cranberry juice (P < 0.05). Quinic, malic, shikimic, and citric acid, the preponderant organic acids in cranberry juice, were tested in combination and individually. The four organic acids also decreased bacterial levels in the bladder when administered together (P < 0.001), and so did the combination of malic plus citric acid (P < 0.01) and malic plus quinic acid (P < 0.05). The other tested combinations of the organic acids, and the acids administered singly, did not have any effect in the UTI model. Apparently, the antibacterial effect of the organic acids from cranberry juice on UTI can be obtained by administering a combination of malic acid and either citric or quinic acid. This study show for the first time that cranberry juice reduce E. coli colonization of the bladder in an experimental mouse model of urinary tract infection and that the organic acids are active agents.

Cranberry Juice Concentrate does not Significantly Decrease the Incidence of Acquired Bacteriuria in Female Hip Fracture Patients Receiving Urine Catheter: a Double-Blind Randomized Trial.

Posted: August 15, 2017
Authors: Gunnarsson AK; Gunningberg L; Larsson S; Jonsson KB.
Journal: Clinical Interventions In Aging. 12:137-143

Abstract: BACKGROUND: Urinary tract infection (UTI) is a common complication among patients with hip fractures. Receiving an indwelling urinary catheter is a risk factor for developing UTIs. Treatment of symptomatic UTIs with antibiotics is expensive and can result in the development of antimicrobial resistance. Cranberries are thought to prevent UTI. There is no previous research on this potential effect in patients with hip fracture who receive urinary catheters. AIM: The aim of this study is to investigate whether intake of cranberry juice concentrate pre-operatively decreases the incidence of postoperative UTIs in hip fracture patients that received a urinary catheter. DESIGN: This study employed a randomized, placebo-controlled double-blind trial. METHOD: Female patients, aged 60 years and older, with hip fracture (n=227) were randomized to receive cranberry or placebo capsules daily, from admission, until 5 days postoperatively. Urine cultures were obtained at admission, 5 and 14 days postoperatively. In addition, Euro Qual five Dimensions assessments were performed and patients were screened for UTI symptoms. RESULT: In the intention-to-treat analysis, there was no difference between the groups in the proportion of patients with hospital-acquired postoperative positive urine cultures at any time point. When limiting the analysis to patients that ingested at least 80% of the prescribed capsules, 13 of 33 (39%) in the placebo group and 13 of 47 (28%) in the cranberry group (P=0.270) had a positive urine culture at 5 days postoperatively. However, this difference was not statistically significant (P=0.270). CONCLUSION: Cranberry concentrate does not seem to effectively prevent UTIs in female patients with hip fracture and indwelling urinary catheter.

Effect of Cranberry Extract on the Frequency of Bacteriuria in Dogs with Acute Thoracolumbar Disk Herniation: A Randomized Controlled Clinical Trial.

Posted: August 15, 2017
Authors: Olby NJ; Vaden SL; Williams K; Griffith EH; Harris T; Mariani CL; Munana KR; Early PJ; Platt SR; Boozer L; Giovanella C; Longshore R.
Journal: Journal of Veterinary Internal Medicine. 31(1):60-68

Abstract: BACKGROUND: Dogs with spinal cord injury are at increased risk of developing bacteriuria due to increased residual urine volume. Cranberry extract inhibits binding of E. coli to uroepithelial cells, potentially reducing risk of bacteriuria. HYPOTHESIS: Cranberry extract reduces risk of bacteriuria in dogs after acute TL-IVDH. ANIMALS: Client-owned dogs with acute onset TL-IVDH causing nonambulatory status. METHODS: Randomized, placebo-controlled, blinded, prospective clinical trial. Dogs with acute TL-IVDH were recruited 48 hours postoperatively and randomized to receive cranberry extract or placebo in a masked fashion. Urine cultures and neurological examinations were performed 2, 4, and 6 weeks postoperatively. The number of dogs with bacteriuria (all bacterial species) and bacteriuria (E. coli) were primary and secondary outcome measures and were evaluated using chi-squared test. Urine antiadhesion activity (AAA) was measured in a subset (N = 47) and examined in a secondary analysis evaluating additional risk factors for bacteriuria. RESULTS: Bacteriuria was detected 17 times in 94 dogs (6 placebo, 11 cranberry, P = .12). There were 7 E. coli. positive cultures (1 placebo, 6 cranberry, P = .09). Dogs in both groups had positive urine AAA (14/21: placebo, 16/26: cranberry), and dogs with urine AAA had significantly fewer E. coli positive cultures (n = 1) than dogs without it (n = 4) (P = .047). CONCLUSIONS AND CLINICAL IMPORTANCE: This clinical trial did not show a benefit of oral cranberry extract but had low power. Cranberry extract supplementation did not impact urine AAA, but a possible association between urine AAA and lower risk of E. coli bacteriuria was identified. Other doses could be investigated.

Effect of Sweetened Dried Cranberry Consumption on Urinary Proteome and Fecal Microbiome in Healthy Human Subjects.

Posted: August 15, 2017
Authors: Bekiares N; Krueger CG; Meudt JJ; Shanmuganayagam D; Reed JD.
Journal: OMICS: A Journal of Integrative Biology DOI: 10.1089/omi.2016.016

Abstract: The relationship among diet, human health, and disease is an area of growing interest in biomarker research. Previous studies suggest that the consumption of cranberries (Vaccinium macrocarpon) could beneficially influence urinary and digestive health. The present study sought to determine if daily consumption of sweetened dried cranberries (SDC) changes the urinary proteome and fecal microbiome, as determined in a prospective sample of 10 healthy individuals. Baseline urine and fecal samples were collected from the subjects in the fasted (8-12h) state. The subjects then consumed one serving (42g) of SDC daily with lunch for 2 weeks. Urine and fecal samples were collected again the day after 2 weeks of SDC consumption. Orbitrap Q-Exactive mass spectrometry of urinary proteins showed that consumption of SDC resulted in changes to 22 urinary proteins. Multiplex sequencing of 16S ribosomal RNA genes in fecal samples indicated changes in relative abundance of several bacterial taxonomic units after consumption of SDC. There was a shift in the Firmicutes:Bacteroidetes ratio, increases in commensal bacteria, and decreases or the absence of bacteria associated with negative health effects. A decrease in uromodulin in all subjects and an increase in Akkermansia bacteria in most subjects were observed and warrant further investigation. Future larger clinical studies with multiomics and multitissue sampling designs are required to determine the effects of SDC consumption on nutrition and health.

Effects of Cranberry (Vaccinum Macrocarpon) Supplementation on Iron Status and Inflammatory Markers in Rowers.

Posted: August 15, 2017
Authors: Skarpanska-Stejnborn, A. Basta, P. Trzeciak, J. Michalska, A. Kafkas, M. E. Woitas-Slubowska, D.
Journal: Journal of the International Society of Sports Nutrition 14(7)

Abstract: Background: The aim of this study was to analyze the effect of supplementation with cranberry (Vaccinum macrocarpon) on the levels of pro-inflammatory cytokines, hepcidin and selected markers of iron metabolism in rowers subjected to exhaustive exercise. Methods: This double-blind study included 16 members of the Polish Rowing Team. The subjects were randomly assigned to the supplemented group (n=9), receiving 1200 mg of cranberry extract for 6 weeks, or to the placebo group (n=7). The participants performed a 2000-m test on a rowing ergometer at the beginning and at the end of the preparatory camp. Blood samples were obtained from the antecubital vein prior to each exercise test, one minute after completing the test, and after a 24-h recovery period. The levels of hepcidin, interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-alpha), ferritin, iron, soluble transferrin receptor (sTfR) and myoglobin were determined, along with total iron-binding capacity (TIBC), unbound iron-binding capacity (UIBC) and total antioxidant capacity (TAC). Results: Both prior and after the supplementation, a significant post-exercise increase in the concentration of IL-6 was observed in both groups. At the end of the study period, cranberry-supplemented athletes presented with significantly higher resting, post-exercise and post-recovery levels of TAC than the controls. However, a significant exercise-induced increase in the concentrations of TNF-alpha, myoglobin and hepcidin was observed solely in the control group. Conclusion: Supplementation with cranberry extract contributed to a significant strengthening of antioxidant potential in individuals exposed to strenuous physical exercise. However, supplementation did not exert direct effects on other analyzed parameters: inflammatory markers and indices of iron metabolism (TNF-alpha, hepcidin and myoglobin).

Effects of Cranberry Extracts on Gene Expression in THP-1 Cells.

Posted: August 15, 2017
Authors: Hannon DB; Thompson JT; Khoo C; Juturu V; Vanden Heuvel JP.
Journal: Food Sciences and Nutrition. 5(1):148-159

Abstract: Cranberry contains high levels of nutrients and bioactive molecules that have health-promoting properties. The purpose of the present studies was to determine if cranberry extracts (CEs) contain phytochemicals that exert anti-inflammatory effects. The human monocytic cell line THP-1 was treated with two CEs (CE and 90MX) and subsequently challenged with Lipopolysaccharides (LPS). Tumor necrosis factor alpha (TNF alpha) expression was decreased in the CE-treated cells, indicative of an anti-inflammatory effect. Gene expression microarrays identified several immune-related genes that were responsive to CEs including interferon-induced protein with tetratricopeptide repeats 1 and 3 (IFIT 1 and 3), macrophage scavenger receptor 1 (MSR1) and colony-stimulating factor 2 (CSF2). In addition, in the CE-treated cells, metallothionein 1F and other metal-responsive genes were induced. Taken together, this data indicates that CEs contain bioactive components that have anti-inflammatory effects and may protect cells from oxidative damage.

Enteric-Coated and Highly Standardized Cranberry Extract Reduces Antibiotic and Nonsteroidal Anti-Inflammatory Drug Use for Urinary Tract Infections During Radiotherapy for Prostate Carcinoma.

Posted: August 15, 2017
Authors: Bonetta A; Roviello G; Generali D; Zanotti L; Cappelletti MR; Pacifico C; Di Pierro F.
Journal: Research & Reports in Urology. 9:65-69

Abstract: INTRODUCTION: Worldwide, bacterial resistance to antibiotic therapy is a major concern for the medical community. Antibiotic resistance mainly affects Gram-negative bacteria that are an important cause of lower urinary tract infections (LUTIs). Pelvic irradiation for prostate cancer is a risk factor for LUTIs. Cranberry extract is reported to reduce the incidence of LUTIs. The prophylactic role of an enteric-coated, highly standardized cranberry extract (VO370) in reducing LUTI episodes, urinary discomfort, and nonsteroidal anti-inflammatory drug (NSAID) and antibiotic use during radiotherapy for prostate carcinoma was evaluated.METHODS: A total of 924 patients with prostate carcinoma treated by radiotherapy to the prostatic and pelvic areas were randomized to receive (n=489) or not (n=435) the enteric-coated, highly standardized cranberry extract for 6-7 weeks concurrently with irradiation. Outcomes were analyzed by using Mann-Whitney U test and Pearson's chi2 test. Primary endpoint was the number of patients with LUTI; secondary endpoints were incidence of recurrence, days of treatment with antibiotics and number of subjects treated with NSAIDs, and incidence of dysuria.RESULTS: The treatment was very well tolerated, and there were no serious side effects. All enrolled patients completed the study. Urinary infections were detected in 53 of the 489 patients (10.8%) treated with enteric-coated, highly standardized cranberry extract, while 107 of the 435 patients (24.6%) in the control group developed LUTIs (p=0.0001). A clear and significant reduction in urinary discomfort of ~50% was seen in treated subjects. The treatment also resulted in ~50% reduction in the use of anti-inflammatory drugs and antibiotics. CONCLUSION: The enteric-coated, highly standardized cranberry extract could be used as a prophylactic to reduce the incidence of LUTIs and decrease antibiotic therapy in patients receiving pelvic irradiation for prostate cancer.

Evaluation of the Effects of a Natural Dietary Supplement with Cranberry, Noxamicina® and D-Mannose in Recurrent Urinary Infections in Perimenopausal Women] [Article In Italian]

Posted: August 15, 2017
Authors: De Leo V, Cappelli V, Massaro MG, Tosti C, Morgante G.
Journal: Minerva Ginecol. 69(4):336-341

Abstract: BACKGROUND:The female genital apparatus, the urinary tract and the perineal supporting tissues share a common embryological origin, whose differentiation depends on the action of estrogens. In adult women, the progressive decline of the ovarian function, with the ensuing estrogen deprivation, reduces tissue tropism causing urogenital atrophy, which makes these organs much more susceptible to traumatisms and urinary infections. The disorders associated with changes in the urogenital tract of peri- and postmenopausal women have significant clinical relevance, both on account of their chronicity and high frequency of occurrence and on account of their having major repercussions on the quality of life of the women, who often have to call their doctor seeking relief for their symptoms. In general, these patients report having a significant number of episodes of cystitis per year. With a view to verifying whether the use of a new dietary supplement (Kistinox® Forte sachets) containing cranberry (Vaccinium macrocarpon), Noxamicina® (propolis extract) and D-mannose can be of use in the treatment of cystitis, with or without bacteriuria, through the elimination of urinary symptoms, a multicenter clinical study was conducted on 150 women aged 40 to 50 suffering from recurrent episodes of cystitis as attested by at least one positive urine culture during the six months preceding their recruitment.METHODS:The subjects were randomly assigned to two groups: Group A: 100 women were given Kistinox® Forte, 1 sachet per day during the first 10 days of the month, for 3 months; Group B: 50 women did not receive any treatment to serve as a control group.RESULTS:The results of the present study show a complete remission of urinary symptoms in 92 women; a slight decrease in urinary symptoms was observed in 5 subjects, whereas 3 women who stopped the treatment after the first cycle were considered drop-outs.CONCLUSIONS:This multicenter clinical study revealed the excellent efficacy and tolerability of Kistinox® Forte sachets in the treatment and prevention of urinary disorders in peri- and postmenopausal women. The posology of a sachet a day during the first 10 days of the month for 3 months was well tolerated by the patients, who did not report any disorder arising from the product.

Evidence of Some Natural Products with Antigenotoxic Effects. Part 1: Fruits and Polysaccharides

Posted: August 15, 2017
Authors: Evidence of Some Natural Products with Antigenotoxic Effects. Part 1: Fruits and Polysaccharides
Journal: Nutrients 9(2)

Abstract: Cancer is one of the leading causes of deaths worldwide. The agents capable of causing damage to genetic material are known as genotoxins and, according to their mode of action, are classified into mutagens, carcinogens or teratogens. Genotoxins are involved in the pathogenesis of several chronic degenerative diseases including hepatic, neurodegenerative and cardiovascular disorders, diabetes, arthritis, cancer, chronic inflammation and ageing. In recent decades, researchers have found novel bioactive phytocompounds able to counteract the effects of physical and chemical mutagens. Several studies have shown potential antigenotoxicity in a variety of fruits. In this review (Part 1), we present an overview of research conducted on some fruits (grapefruit, cranberries, pomegranate, guava, pineapple, and mango) which are frequentl consumed by humans, as well as the analysis of some phytochemicals extracted from fruits and yeasts which have demonstrated antigenotoxic capacity in various tests, including the Ames assay, sister chromatid exchange, chromosomal aberrations, micronucleus and comet assay.

Formulation of Thermoreversible Gel of Cranberry Juice Concentrate: Evaluation, Biocompatibility Studies and its Antimicrobial Activity Against Periodontal Pathogens.

Posted: August 15, 2017
Authors: Rajeshwari HR; Dhamecha D; Jagwani S; Patil D; Hegde S; Potdar R; Metgud R; Jalalpure S; Roy S; Jadhav K; Tiwari NK; Koduru S; Hugar S; Dodamani S.
Journal: Materials Science & Engineering. C, Materials for Biological Applications. 75:1506-1514

Abstract: The present work aims to investigate the efficacy of thermoreversible gel of cranberry juice concentrate (CJC) as local drug delivery for the treatment of periodontitis. CJC was initially tested for its antimicrobial activities like MIC, MBC, antiadhesion, antibiofilm and time kill assay against the panel of organisms (S. mutans (SM), E. faecalis (EF), A. actinomycetemcomitans (AA), P. gingivalis (PG), T. forsythia (TF)) responsible for periapical and periodontal infections. Antimicrobial activity of CJC showed MIC value of 50mg/ml and MBC value of 100mg/ml with desirable antiadhesion (83-90%) and antibiofilm activity (70-85%). CJC was evaluated for its biocompatibility using periodontal fibroblasts by cell based MTT assay and found to be nontoxic. Influence of CJC on periodontopathogen PG derived virulence factors (fimA and kgp) was studied using real time polymerase chain reaction (RT-PCR) technique wherein down regulation of selected genes demonstrated inhibitory effect against PG virulence factors. Thermoreversible gel of CJC was formulated by cold method using poloxamer 407 as thermosensitive polymer and carbopol 934 as mucoadhesive polymer and evaluated for its gelation temperature, viscosity, gel strength and mucoadhesive strength. Comparison of optimized thermoreversible gel of CJC (500mg/ml) with commercially available chlorhexidine gluconate gel (0.2%) using agar well diffusion demonstrated equal zone of inhibition against SM, EF, AA, PG & TF. Hence the formulated thermoreversible gel of CJC could serve as a novel herbal alternative to currently available periodontal treatment modalities.

Highly Standardized Cranberry Extract Supplementation (Anthocran®) as Prophylaxis in Young Healthy Subjects with Recurrent Urinary Tract Infections

Posted: August 15, 2017
Authors: Ledda A, Belcaro G, Dugall M, Riva A, Togni S, Eggenhoffner R, Giacomelli L.
Journal: Eur Rev Med Pharmacol Sci. 21(2):389-393

Abstract: OBJECTIVE:Several studies have investigated the role of cranberry extract in the prevention of recurrent urinary tract infections (UTIs), on different selected subpopulations at increased risk of UTI. In this registry, we tested the prophylactic effects of an oral supplementation containing a highly standardized cranberry extract (Anthocran®) in young subjects with a previous history of recurrent UTIs, over a 2-months follow-up.PATIENTS AND METHODS:36 otherwise healthy subjects in juvenile age (between 12 and 18 years of age) suffering by recurrent UTIs were enrolled. Participants received either a standard management (SM) (control group, n=17) or SM associated with an oral daily supplementation (supplementation group, n=19). Oral supplementation consisted in one capsule containing 120 mg of cranberry extract (Anthocran®), standardized to 36 mg proanthocyanidins, for 60 days. The effectiveness in the prevention of UTIs was determined by: the number of UTIs evaluated two months before the inclusion in the registry and during the supplementation period; the number of symptom-free subjects during the registry period. Safety considerations and measurement of adherence to treatment were also performed.RESULTS:The two groups were comparable for age, gender distribution, the days of follow-up and also for the number of UTIs before inclusion. The mean number of UTIs observed during the registry in the supplemented group (0.31±0.2) was significantly lower compared to the control group (2.3±1.3) and to the mean number of UTIs assessed before inclusion (1.74±1.1) (p-value = 0.0001 for both). Moreover, 63.1% of supplemented subjects was symptom-free during the registry period, whereas 23.5% subjects were asymptomatic in the control group (p-value <0.05).CONCLUSIONS:This registry supplement study provides compelling evidence on the efficacy of an oral supplementation, based on a highly standardized cranberry extract (Anthocran®), as prophylaxis in young healthy subjects suffering by recurrent UTIs.

Mechanism of Anti-rotavirus Synergistic Activity by Epigallocatechin Gallate and a Proanthocyanidin-Containing Nutraceutical.

Posted: August 15, 2017
Authors: Lipson SM; Karalis G; Karthikeyan L; Ozen FS; Gordon RE; Ponnala S; Bao J; Samarrai W; Wolfe E.
Journal: Food & Environmental Virology DOI 10.1007/s12560-017-9299-z

Abstract: Epigallocatechin gallate (EGCG) of green tea and the nutraceutical CystiCran-40 (containing 40% proanthocyanidins) of the cranberry plant have been associated with antiviral activity. The purpose of this work was to determine the mechanism of antiviral synergy between each compound. Coliphage T4II (phage T4) and the rotavirus strain SA-11(RTV) were used as model virus systems. Individual and combined flavonoids structural and molecular weight analyses were performed by NMR and HPCL/MS, respectively. A suboptimal concentration of EGCG or C-40 alone or in combination reduced phage infectivity by <=10%. Similarly, EGCG (30 micro g/ml) and C-40 (25 micro g/ml), respectively, reduced RTV titers by 3 and 13%. However, RTV titers were reduced by 32% (p < .05) with both flavonoids used in combination. RTV was not recognized in host cells by electron microscopy 24-h post-inoculation. NMR and HPLC/MS findings revealed significant structural and potential changes in molecular weight of the flavonoids in complex.

Medicinal Plants with Multiple Effects on Cardiovascular Diseases: A Systematic Review.

Posted: August 15, 2017
Authors: Rouhi-Boroujeni H; Heidarian E; Rouhi-Boroujeni H; Deris F; Rafieian-Kopaei M.
Journal: Current Pharmaceutical Design. 23(7):999-1015

Abstract: INTRODUCTION: Hyperlipidemia, obesity, hypertension, and diabetes are the most important risk factors for cardiovascular diseases. The aim of this systematic review article is to introduce the medicinal plants that exert significant clinical effects on hypertension, hyperlipidemia, obesity, and diabetes. METHODS: In this review article, the international research databases including MEDLINE, Google scholar, EBSCO, Academic Search, Web of Science, SciVerse, Scopus (SCOPUS), EBSCO, Academic Search, Cochrane, Central Register of Controlled Trials (CENTRAL) and a Chinese database (China Network Knowledge Infrastructure [CNKI]) were searched using the key words hyperlipidemia, hypertension, diabetes, herbal, obesity, and phytomedicine, matched by MESH, from their respective inceptions up to March, 2016. The plants that were effective on one, two, three, or all of four diseases were determined. The doses, side effects, the most important pharmaceutically effective compounds, the used organs, and important points regarding usage were separately recorded. Also known clinically significant interactions were presented. RESULTS: 1023 articles were found to be about medicinal plants and hypertension, 1912 articles about medicinal plants and hyperlipidemia, 810 articles about medicinal plants and obesity, 1174 articles about medicinal plants and diabetes. Of 144 plants included in the analysis, 83 were found to be effective on hyperlipidemia, 100 on hypertension, 66 on obesity, and 72 on diabetes. 43 plants were found to be effective on two diseases, 14 on three diseases, and 34 on all four diseases. Three plants (Tomato, Cranberry and Pomegranate), in food and therapeutic doses, were found to be used to treat cardiovascular diseases especially in pre-eclampsia and hyperlipidemia in pregnancy. CONCLUSION: Regarding the findings of this study, we can argue that the medicinal plants, other than monotherapy, can be used as poly-therapy, to treat cardiovascular diseases.

Morphometric Abnormalities in Spleen and Kidney of the Progeny of Mice Fed American Cranberry Extract (Vaccinium macrocarpon) During Pregnancy and Lactation.

Posted: August 15, 2017
Authors: Ba&#322;an BJ, Lewicki S, Siwicki AK, Stelmasiak M, Skopi&#324;ski P, Skopi&#324;ska-Ró&#380;ewska E, Wasiuty&#324;ski A, Zdanowski R.
Journal: Pol J Vet Sci. 20(1):57-65

Abstract: Cranberries and cranberry-derived diet supplements are often recommended for the treatment of urinary tract infections, also during pregnancy. These products contain strongly anti-angiogenic chemical compounds which could not be indifferent to the developing fetus. In the present work we evaluated the effect of feeding pregnant and lactating mice American cranberry extract (daily dose 0.88 mg) on the morphology and some parameters of spleen and kidney function of their adult progeny. Six weeks after delivery the morphometry of spleen and kidney, cytometric analysis of spleen lymphocytes, evaluation of humoral response to SRBC (Sheep Red Blood Cells), and examination of serum creatinine/urea concentration, were performed in the offspring. Spleens of progeny from experimental (E) group differed from the spleens of progeny of control mice in the lower number of lymphatic nodules and their larger diameter. Cytometry of spleen cells from progeny of E mothers revealed more CD19+ and CD8+ lymphocytes than in the control group. No difference was seen in the response to immunization by red blood cells of sheep (SRBC) between control and E offspring. An increase in the diameter of glomeruli was observed in the kidneys of the experimental group in comparison with the control group. No abnormalities in creatinine and urea serum level were observed. A higher concentration of VEGF and bFGF in E offspring sera in comparison to the controls was seen. CONCLUSION: Although the observed differences between the control and experimental group were not large, caution is recommended in using cranberries and their extracts during pregnancy until more research will be done on this topic.

Multidimensional Comparative Analysis of Phenolic Compounds in Organic Juices with High Antioxidant Capacity.

Posted: August 15, 2017
Authors: Nowak D; Goslinski M; Szwengiel A.
Journal: Journal of the Science of Food & Agriculture. 97(8):2657-2663

Abstract: BACKGROUND: A diet rich in fruit, vegetables and juices is associated with health benefit and reduced risk of certain civilization diseases. Antioxidant properties depend mainly on the total content of polyphenols and their composition. The aim of this study was to perform a multidimensional comparative analysis of phenolic compounds of organic juices with high antioxidant capacity (chokeberry, elderberry, cranberry, pomegranate).RESULTS: All the analyzed juices were a rich source of phenolic compounds. Chokeberry juices had the highest total polyphenol content (up to 7900 mg GAE L-1 ). These juices as well as pomegranate juice were characterized by the highest antioxidant capacity (~5000 mg Trolox equivalents L-1 ). Other samples had lower total polyphenols content and total antioxidant capacity. Multidimensional analysis of the profiles of phenolic compounds showed that chokeberry juices differ from the other juices. Cranberry and pomegranate juices were similar to each other, and elderberry juice was closer to these samples than to chokeberry. The predominant polyphenols of chokeberry juices were anthocyanins (especially cyanidin-3-galactoside and cyanidin-3-arabinoside) and phenolic acids (chlorogenic and neochlorogenic acid). Elderberry juice was an exception by having flavonols (quercetin derivatives) as the principal compounds.CONCLUSION: Chokeberry juices were characterized by the highest antioxidant properties, which predispose them to further clinical research concerning the supporting cardiovascular disease prophylaxis

Oral Pharmacokinetic Interaction of Ester Rich Fruit Juices and Pharmaceutical Excipients with Tenofovir Disoproxil Fumarate in Male Wistar Rats.

Posted: August 15, 2017
Authors: Shailender J; Ravi PR; Saha P; Myneni S.
Journal: Xenobiotica http://dx.doi.org/10.1080/00498254.2016.1269375

Abstract: 1. The aim of this study was to evaluate the role of intestinal esterases on the absorption process of tenofovir disoproxil fumarate (TDF). 2. The esterase inhibition capacity of fruit juices (FJs) rich in ester linkages and pharmaceutical excipients (having ester bonds) was performed in vitro by incubating TDF with each FJ and excipient in the intestinal washings. The ex vivo everted gut sac model was also used to evaluate the absorption enhancement capacity of these FJs and excipients. Single-dose oral pharmacokinetic studies were performed by concomitant administration of TDF with each of the selected FJs and excipients. 3. The in vitro and ex vivo studies showed that cremophor-EL and all FJs prevented the metabolism of TDF with grapefruit juice (GFJ) having the highest level of inhibition. Further, the permeability flux of the monoester form of tenofovir was increased by 113% and 212% by cranberry juice (CBJ) and GFJ, respectively. The in vivo studies also showed that both CBJ and GFJ enhanced the oral bioavailability of TDF as the AUC was increased by 24% and 97%, respectively. 4. These results indicate that the prevention of the metabolic conversion of TDF to its monoester form is crucial in increasing the oral absorption of TDF.

Photoprotective Effects of Cranberry Juice and its Various Fractions Against Blue Light-Induced Impairment in Human Retinal Pigment Epithelial Cells.

Posted: August 15, 2017
Authors: Chang CH, Chiu HF, Han YC, Chen IH, Shen YC, Venkatakrishnan K, Wang CK.
Journal: Pharm Biol. 55(1):571-580.

Abstract: CONTEXT:Cranberry has numerous biological activities, including antioxidation, anticancer, cardioprotection, as well as treatment of urinary tract infection (UTI), attributed to abundant phenolic contents.OBJECTIVE:The current study focused on the effect of cranberry juice (CJ) on blue light exposed human retinal pigment epithelial (ARPE-19) cells which mimic age-related macular degeneration (AMD).MATERIALS AND METHODS:Preliminary phytochemical and HPLC analysis, as well as total antioxidant capacity and scavenging activity of cranberry ethyl acetate extract and different CJ fractions (condensed tannins containing fraction), were evaluated. In cell line model, ARPE-19 were irradiated with blue light at 450&#8201;nm wavelength for 10&#8201;h (mimic AMD) and treated with different fractions of CJ extract at different doses (5-50&#8201;&#956;g/mL) by assessing the cell viability or proliferation rate using MTT assay (repairing efficacy).RESULTS:Phytochemical and HPLC analysis reveals the presence of several phenolic compounds (flavonoids, proanthocyanidin, quercetin) in ethyl acetate extract and different fractions of CJ. However, the condensed tannin containing fraction of ethyl acetate extract of CJ displayed the greater (p&#8201;<&#8201;0.05) scavenging activity especially at the dose of 1&#8201;mg/mL. Similarly, the condensed tannin containing fraction at 50&#8201;&#956;g/mL presented better (p&#8201;<&#8201;0.05) repairing ability (increased cell viability). Furthermore, the oligomeric condensed tannin containing fraction display the best (p&#8201;<&#8201;0.05) repairing efficiency at 50&#8201;&#956;g/mL.DISCUSSION AND CONCLUSION:In conclusion, this study distinctly proved that condensed tannin containing fraction of CJ probably exhibits better free radicals scavenging activity and thereby effectively protected the ARPE-19 cells and thus, hampers the progress of AMD.

Polyphenol Interactions Mitigate the Immunogenicity and Allergenicity of Gliadins.

Posted: August 15, 2017
Authors: Perot M; Lupi R; Guyot S; Delayre-Orthez C; Gadonna-Widehem P; Thebaudin JY; Bodinier M; Larre C.
Journal: Journal of Agricultural & Food Chemistry. 65(31):6442-6451

Abstract: Wheat allergy is an IgE-mediated disorder. Polyphenols, which are known to interact with certain proteins, could be used to reduce allergic reactions. This study screened several polyphenol sources for their ability to interact with gliadins, mask epitopes, and affect basophil degranulation. Polyphenol extracts from artichoke leaves, cranberries, apples, and green tea leaves were examined. Of these extracts, the first three formed insoluble complexes with gliadins. Only the cranberry and apple extracts masked epitopes in dot blot assays using anti-gliadin IgG and IgE antibodies from patients with wheat allergies. The cranberry and artichoke extracts limited cellular degranulation by reducing mouse anti-gliadin IgE recognition. In conclusion, the cranberry extract is the most effective polyphenol source at reducing the immunogenicity and allergenicity of wheat gliadins.

Protein-Bound Vaccinium Fruit Polyphenols Decrease IgE Binding to Peanut Allergens and RBL-2H3 Mast Cell Degranulation In Vitro.

Posted: August 15, 2017
Authors: Plundrich, N. J. Bansode, R. R. Foegeding, E. A. Williams, L. L. Lila, M. A.
Journal: Food and Function 8(4):1611-1621

Abstract: Peanut allergy is a worldwide health concern. In this study, the natural binding properties of plant-derived polyphenols to proteins was leveraged to produce stable protein-polyphenol complexes comprised of peanut proteins and cranberry (Vaccinium macrocarpon Ait.) or lowbush blueberry (Vaccinium angustifolium Ait.) pomace polyphenols. Protein-bound and free polyphenols were characterized and quantified by multistep extraction of polyphenols from protein-polyphenol complexes. Immunoblotting was performed with peanut-allergic plasma to determine peanut protein-specific IgE binding to unmodified peanut protein, or to peanut protein-polyphenol complexes. In an allergen model system, RBL-2H3 mast cells were exposed to peanut protein-polyphenol complexes and evaluated for their inhibitory activity on ionomycin-induced degranulation ( beta -hexosaminidase and histamine). Among the evaluated polyphenolic compounds from protein-polyphenol complex eluates, quercetin, - in aglycone or glycosidic form - was the main phytochemical identified to be covalently bound to peanut proteins. Peanut protein-bound cranberry and blueberry polyphenols significantly decreased IgE binding to peanut proteins at p<0.05 (38% and 31% decrease, respectively). Sensitized RBL-2H3 cells challenged with antigen and ionomycin in the presence of protein-cranberry and blueberry polyphenol complexes showed a significant (p<0.05) reduction in histamine and beta -hexosaminidase release (histamine: 65.5% and 65.8% decrease; beta -hexosaminidase: 60.7% and 45.4% decrease, respectively). The modification of peanut proteins with cranberry or blueberry polyphenols led to the formation of peanut protein-polyphenol complexes with significantly reduced allergenic potential. Future trials are warranted to investigate the immunomodulatory mechanisms of these protein-polyphenol complexes and the role of quercetin in their hypoallergenic potential.

Strawberry and Cranberry Polyphenols Improve Insulin Sensitivity in Insulin-Resistant, Non-Diabetic Adults: a Parallel, Double-Blind, Controlled and Randomised Clinical Trial.

Posted: August 15, 2017
Authors: Paquette M, Medina Larqué AS, Weisnagel SJ, Desjardins Y, Marois J, Pilon G, Dudonné S, Marette A, Jacques H.
Journal: Br J Nutr.117(4):519-531

Abstract: Plant-derived foods rich in polyphenols are associated with several cardiometabolic health benefits, such as reduced postprandial hyperglycaemia. However, their impact on whole-body insulin sensitivity using the hyperinsulinaemic-euglycaemic clamp technique remains under-studied. We aimed to determine the effects of strawberry and cranberry polyphenols (SCP) on insulin sensitivity, glucose tolerance, insulin secretion, lipid profile, inflammation and oxidative stress markers in free-living insulin-resistant overweight or obese human subjects (n 41) in a parallel, double-blind, controlled and randomised clinical trial. The experimental group consumed an SCP beverage (333 mg SCP) daily for 6 weeks, whereas the Control group received a flavour-matched Control beverage that contained 0 mg SCP. At the beginning and at the end of the experimental period, insulin sensitivity was assessed by a hyperinsulinaemic-euglycaemic clamp, and glucose tolerance and insulin secretion by a 2-h oral glucose tolerance test (OGTT). Insulin sensitivity increased in the SCP group as compared with the Control group (+0·9 (sem 0·5)×10-3 v. -0·5 (sem 0·5)×10-3 mg/kg per min per pmol, respectively, P=0·03). Compared with the Control group, the SCP group had a lower first-phase insulin secretion response as measured by C-peptide levels during the first 30 min of the OGTT (P=0·002). No differences were detected between the two groups for lipids and markers of inflammation and oxidative stress. A 6-week dietary intervention with 333 mg of polyphenols from strawberries and cranberries improved insulin sensitivity in overweight and obese non-diabetic, insulin-resistant human subjects but was not effective in improving other cardiometabolic risk factors.

UHPLC-Q-Orbitrap-HRMS-Based Global Metabolomics Reveal Metabolome Modifications in Plasma of Young Women after Cranberry Juice Consumption.

Posted: August 15, 2017
Authors: Liu H; Garrett TJ; Su Z; Khoo C; Gu L.
Journal: Journal of Nutritional Biochemistry. 45:67-76

Abstract: Plasma metabolome in young women following cranberry juice consumption were investigated using a global UHPLC-Q-Orbitrap-HRMS approach. Seventeen female college students, between 21 and 29 years old, were given either cranberry juice or apple juice for three days using a cross-over design. Plasma samples were collected before and after juice consumption. Plasma metabolomes were analyzed using UHPLC-Q-Orbitrap-HRMS followed by orthogonal partial least squares-discriminant analyses (OPLS-DA). S-plot was used to identify discriminant metabolites. Validated OPLS-DA analyses showed that the plasma metabolome in young women, including both exogenous and endogenous metabolites, were altered following cranberry juice consumption. Cranberry juice caused increases of exogenous metabolites including quinic acid, vanilloloside, catechol sulfate, 3,4-dihydroxyphenyl ethanol sulfate, coumaric acid sulfate, ferulic acid sulfate, 5-(trihydroxphenyl)-gamma-valerolactone, 3-(hydroxyphenyl)proponic acid, hydroxyphenylacetic acid and trihydroxybenzoic acid. In addition, the plasma levels of endogenous metabolites including citramalic acid, aconitic acid, hydroxyoctadecanoic acid, hippuric acid, 2-hydroxyhippuric acid, vanilloylglycine, 4-acetamido-2-aminobutanoic acid, dihydroxyquinoline, and glycerol 3-phosphate were increased in women following cranberry juice consumption. The metabolic differences and discriminant metabolites observed in this study may serve as biomarkers of cranberry juice consumption and explain its health promoting properties in human.

Impact of Cranberries on Gut Microbiota and Cardiometabolic Health: Proceedings of the Cranberry Health Research Conference 2015

Posted: August 3, 2016
Authors: Blumberg JB, Basu A, Krueger CG, Lila MA, Neto CC, Novotny JA, Reed JD, Rodriguez-Mateos A, Toner CD
Journal: Advances in Nutrition. 2016;7:759S-770S. doi: 10.3945/an.116.012583


Recent advances in cranberry research have expanded the evidence for the role of this Vaccinium berry fruit in modulating gut microbiota function and cardiometabolic risk factors. The A-type structure of cranberry proanthocyanidins seems to be responsible for much of this fruit’s efficacy as a natural antimicrobial. Cranberry proanthocyanidins interfere with colonization of the gut by extraintestinal pathogenic Escherichia coli in vitro and attenuate gut barrier dysfunction caused by dietary insults in vivo. Furthermore, new studies indicate synergy between these proanthocyanidins, other cranberry components such as isoprenoids and xyloglucans, and gut microbiota. Together, cranberry constituents and their bioactive catabolites have been found to contribute to mechanisms affecting bacterial adhesion, coaggregation, and biofilm formation that may underlie potential clinical benefits on gastrointestinal and urinary tract infections, as well as on systemic anti-inflammatory actions mediated via the gut microbiome. A limited but growing body of evidence from randomized clinical trials reveals favorable effects of cranberry consumption on measures of cardiometabolic health, including serum lipid profiles, blood pressure, endothelial function, glucoregulation, and a variety of biomarkers of inflammation and oxidative stress. These results warrant further research, particularly studies dedicated to the elucidation of dose-response relations, pharmacokinetic/metabolomics profiles, and relevant biomarkers of action with the use of fully characterized cranberry products. Freeze-dried whole cranberry powder and a matched placebo were recently made available to investigators to facilitate such work, including interlaboratory comparability.

Link to full text article: http://advances.nutrition.org/content/7/4/759S.full