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Cysticlean a highly pac standardized content in the prevention of recurrent urinary tract infections: an observational, prospective cohort study.

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Authors
Sanchez Ballester F, Ruiz Vidal V, Lopez Alcina E, Domenech Perez C, Escudero Fontano E, Oltra Benavent A, Montoliu Garcia A, Sobron Bustamante M
Journal
BMC Urol 13:28
Abstract

BACKGROUND: The present study was aimed at determining the prophylactic efficacy of American cranberry (AC) extract (Cysticlean) in women with recurrent symptomatic postcoital urinary tract infections (PCUTI), non-consumer of AC extract in the past 3 months before inclusion, and to determine changes in their quality of life (QoL).

METHODS: This was a single center, observational, prospective study in a total of 20 women (mean age 35.2 years; 50.0% were married). Patients were followed up for 3 and 6 months during treatment.

RESULTS: The number of PCUTIs in the previous 3 months prior to start the treatment with Cysticlean was 2.8+1.3 and it was reduced to 0.2+0.5 at Month 6 (P0.0001), which represent a 93% improvement. At baseline, the mean score on the VAS scale (range from 0 to 100) for assessing the QoL was 62.4+19.1, increasing to 78.2+12.4 at Month 6 (P=0.0002), which represents a 20% improvement. All patients had an infection with positive urine culture at baseline, after 6 months there were only 3 symptomatic infections (P0.001). The most common bacterium was Escherichia coli.

CONCLUSIONS: Prophylaxis with American cranberry extract (Cysticlean) could be an alternative to classical therapies with antibiotics. Further studies are needed to confirm results obtained in this pilot study.

Development and validation of a sensitive, high-throughput bioassay for the adhesion of radiolabeled E. coli to uroepithelial cells in vitro.

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Authors
Mathison BD, Kimble LL, Kaspar KL, Khoo C, Chew BP
Journal
J Nat Prod 76(9):1605-11
Abstract

Vaccinium macrocarpon (cranberry) products have been used to prevent uropathogenic Escherichia (E.) coli adherence to uroepithelial cells (UEC) and may help reduce risk of urinary tract infection. Reported herein are the development and validation of an assay to assess antiadhesion activity of V. macrocarpon extracts and human urine. P-fimbriated E. coli (CFT073) was labeled with H-uridine, then co-incubated with HTB-4 UEC at a 400:1 ratio. V. macrocarpon extracts (0-17 mg proanthocyanidins/mL) were added to H-labeled E. coli before co-incubating with UEC. The assay yielded a sensitive inhibition curve: the lower limit of detection and half-maximal inhibitory concentration were 0.43 and 1.59 mg proanthocyanidins/mL for V. macrocarpon extract CEP 55; intra- and interassay coefficients of variance were 10% and 15%, respectively. V. macrocarpon extract CEP 3283 showed identical adhesion inhibition. Serial dilutions of urine from human participants who consumed V. macrocarpon beverages showed a linear decrease in antiadhesion activity. Antiadhesion assays conducted with urine from a human intervention study also showed good agreement with results obtained using the hemagglutination assay. Therefore, a sensitive, high-throughput, biologically relevant antiadhesion assay using H-E. coli co-incubated with UEC is reported, which can be used for studying the action of V. macrocarpon bioactives.

Effects of cranberry powder on biomarkers of oxidative stress and glucose control in db/db mice.

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Authors
Kim MJ, Chung JY, Kim JH, Kwak HK
Journal
Nutr Res Pract 7(6):430-8
Abstract

Increased oxidative stress in obese diabetes may have causal effects on diabetic complications, including dyslipidemia. Lipopolysccharides (LPS) along with an atherogenic diet have been found to increase oxidative stress and insulin resistance. Cranberry has been recognized as having beneficial effects on diseases related to oxidative stress. Therefore, we employed obese diabetic animals treated with an atherogenic diet and LPS, with the aim of examining the effects of cranberry powder (CP) on diabetic related metabolic conditions, including lipid profiles, serum insulin and glucose, and biomarkers of oxidative stress. Forty C57BL/KsJ-db/db mice were divided into the following five groups: normal diet + saline, atherogenic diet + saline, atherogenic diet + LPS, atherogenic diet + 5% CP + LPS, and atherogenic diet + 10% CP + LPS. Consumption of an atherogenic diet resulted in elevation of serum total cholesterol and atherogenic index (AI) and reduction of high density lipoprotein (HDL)-cholesterol. However, with 10% CP, the increase in mean HDL-cholesterol level was close to that of the group with a normal diet, whereas AI was maintained at a higher level than that of the group with a normal diet. LPS induced elevated serum insulin level was lowered by greater than 60% with CP (P 0.05), and mean serum glucose level was reduced by approximately 19% with 5% CP (P > 0.05). Mean activity of liver cytosolic glutathione peroxidase was significantly increased by LPS injection, however it was reduced back to the value without LPS when the diet was fortified with 10% CP (P 0.05). In groups with CP, a reduction in mean levels of serum protein carbonyl tended to occur in a dose dependent manner. Particularly with 10% CP, a reduction of approximately 89% was observed (P > 0.05). Overall results suggest that fortification of the atherogenic diet with CP may have potential health benefits for obese diabetes with high oxidative stress, by modulation of physical conditions, including some biomarkers of oxidative stress.

Inhibition of interleukin-17-stimulated interleukin-6 and -8 production by cranberry components in human gingival fibroblasts and epithelial cells.

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Authors
Tipton DA, Cho S, Zacharia N, Dabbous MK
Journal
J Periodontal Res 48(5):638-46
Abstract

BACKGROUND AND OBJECTIVE: Gingival epithelial cells and fibroblasts participate in periodontal inflammation and destruction, producing interleukin (IL)-6, a regulator of osteoclastic bone resorption, and the neutrophil chemoattractant IL-8. IL-17, a product of T-helper 17 cells, may play a role in periodontitis by stimulating cytokine production by gingival cells. The cranberry (Vaccinium macrocarpon) is rich in polyphenols, particularly proanthocyanidins, which have antioxidant and other beneficial properties. Cranberry components inhibit pro-inflammatory activities of lipopolysaccharide-stimulated human macrophages, gingival fibroblasts, and epithelial cells, but little is known of its effects on IL-17-stimulated cytokine production. The objectives were to determine the effects of IL-17 + cranberry components on IL-6 and IL-8 production by human gingival epithelial cells and fibroblasts.

MATERIAL AND METHODS: Cranberry high molecular weight non-dialyzable material (NDM), which is rich in proanthocyanidins, was derived from cranberry juice. Human gingival epithelial cells and normal human gingival fibroblasts were incubated with NDM (5-50 mug/mL), IL-17 (0.5-100 ng/mL), or NDM + IL-17 in serum-free medium for 6 d. IL-6 and IL-8 in culture supernatants were measured by ELISA. Membrane damage and viability were assessed by lactate dehydrogenase activity released into cell supernatants and activity of a mitochondrial enzyme, respectively. Data were analyzed using ANOVA and Scheffe's F procedure for post hoc comparisons.

RESULTS: In both cell lines, IL-17 (> ~5-10 ng/mL) significantly stimulated production of IL-6 (p 0.005) and IL-8 (p 0.03). Non-toxic levels of NDM inhibited constitutive IL-6 and IL-8 production by epithelial cells (p 0.01) and fibroblasts (p 0.03) as well as IL-17-stimulated cytokine production by epithelial cells [IL-6 (maximum ~80% inhibition; p 0.0001); IL-8 (maximum ~70% inhibition; p 0.03)] and fibroblasts [IL-6 (maximum ~90% inhibition; p 0.0001); IL-8 (maximum ~80% inhibition; p 0.008)].

CONCLUSION: Cranberry NDM inhibition of constitutive and IL-17-stimulated IL-6 and IL-8 production by gingival fibroblasts and epithelial cells suggests that cranberry components could be useful as a host modulatory therapeutic agent to prevent or treat periodontitis. 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Pregnancy outcome after use of cranberry in pregnancy--the Norwegian Mother and Child Cohort Study.

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Authors
Heitmann K, Nordeng H, Holst L
Journal
BMC Altern Med 13:345
Abstract

BACKGROUND: Cranberry is one of the most commonly used herbs during pregnancy. The herb has been used traditionally against urinary tract infections. No studies are found that specifically address the risk of malformations after use of cranberry during pregnancy. The aim of the study was to investigate the safety of cranberry use during pregnancy, including any effects on congenital malformations and selected pregnancy outcomes.

METHODS: The study is based on data from The Norwegian Mother and Child Cohort Study including more than 100,000 pregnancies from 1999 to 2008. Information on use of cranberry and socio-demographic factors was retrieved from three self-administered questionnaires completed by the women in pregnancy weeks 17 and 30, and 6 months after birth. Information on pregnancy outcomes was retrieved from the Medical Birth Registry of Norway.

RESULTS: Among the 68,522 women in the study, 919 (1.3%) women had used cranberry while pregnant. We did not detect any increased risk of congenital malformations after use of cranberry. Furthermore, the use of cranberry was also not associated with increased risk for stillbirth/neonatal death, low birth weight, small for gestational age, preterm birth, low Apgar score (7), neonatal infections or maternal vaginal bleeding in early pregnancy. Although an association was found between use of cranberry in late pregnancy and vaginal bleeding after pregnancy week 17, further sub-analyses of more severe bleeding outcomes did not support a significant risk.

CONCLUSIONS: The findings of this study, revealing no increased risk of malformations nor any of the following pregnancy outcomes; stillbirth/neonatal death, preterm delivery, low birth weight, small for gestational age, low Apgar score and neonatal infections are reassuring. However, maternal vaginal bleeding should be investigated further before any firm conclusion can be drawn. Treatment guidelines on asymptomatic bacteriuria in pregnancy recommend antimicrobial therapy as the first line treatment. According to our data and the outcomes studied, cranberry does not appear to be a harmful adjunctive self-treatment.

Proanthocyanidin A2 purification and quantification of American cranberry (Vaccinium macrocarpon Ait.) products.

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Authors
Lee JM
Journal
J Funct Foods 5(1):144-153
Abstract

In this study, five common proanthocyanidin purification techniques were evaluated prior to phloroglucinolysis, followed by HPLC analysis. An optimized purification method was then used to identify and quantify the proanthocyanidins (extension and terminal units of epigallocatechin, catechin, epicatechin, A type trimer, and A type dimer) of commercially available cranberry products (juices, concentrates, tablets, and capsules; n=17). Two size exclusion beads (Toyopearl 4 TSK HW-40C and Sephadex LH-20) were found suitable for proanthocyanidin purification, though proanthocyanidin extension and terminal unit composition was contingent upon the cleanup procedure utilized. These data illustrate that purification methods require consideration prior to conducting any cranberry proanthocyanidin analyses, and have to be accounted for when comparing values between studies. Total proanthocyanidin levels ranged from 11.7 (juice) to 436.4 (tablet) mg/100 mL or 100 g values obtained from Sephadex LH-20 purification, while total anthocyanin levels ranged from 0.54 (juice) to 98.00 (tablet) mg/100 mL or 100 g.

Quantification by UHPLC of total individual polyphenols in fruit juices.

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Authors
Diaz-Garcia MC, Obon JM, Castellar MR, Collado J, Alacid M
Journal
Food Chem 138(2-3):938-49
Abstract

The present work proposes a new UHPLC-PDA-fluorescence method able to identify and quantify the main polyphenols present in commercial fruit juices in a 28-min chromatogram. The proposed method improve the IFU method No. 71 used to evaluate anthocyanins profiles of fruit juices. Fruit juices of strawberry, American cranberry, bilberry, sour cherry, black grape, orange, and apple, were analysed identifying 70 of their main polyphenols (23 anthocyanins, 15 flavonols, 6 hydroxybenzoic acids, 14 hydroxycinnamic acids, 4 flavanones, 2 dihydrochalcones, 4 flavan-3-ols and 2 stilbenes). One standard polyphenol of each group was used to calculate individual polyphenol concentration presents in a juice. Total amount of polyphenols in a fruit juice was estimated as total individual polyphenols (TIP). A good correlation (r(2)=0.966) was observed between calculated TIP, and total polyphenols (TP) determined by the well-known colorimetric Folin-Ciocalteu method. In this work, the higher TIP value corresponded to bilberry juice (607.324 mg/100mL fruit juice) and the lower to orange juice (32.638 mg/100mL fruit juice). This method is useful for authentication analyses and for labelling total polyphenols contents of commercial fruit juices. Copyright 2012 Elsevier Ltd. All rights reserved.

Quantifying and characterizing proanthocyanidins in cranberries in relation to urinary tract health. [Review]

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Authors
Krueger CG, Reed JD, Feliciano RP Howell AB
Journal
Anal Bioanal Chem 405(13):4385-95
Abstract

The "A-type" proanthocyanidins in cranberry fruit (Vaccinium macrocarpon Ait.) are bioactive components associated with prevention of urinary tract infections (UTI). Cranberry juice, fruit (fresh and dried), functional foods, and cranberry dietary supplements are promoted for prevention of UTI and for maintenance of urinary tract health (UTH), on the basis of their content of cranberry proanthocyanidins (c-PAC) with "A-type" interflavan bonds. With increasing consumer use of cranberries for maintenance of UTH and an expanding number of commercial cranberry products of different types, the availability of unified methods for measuring levels of c-PAC is important. This review discusses quantitative and qualitative analysis of c-PAC with "A-type" interflavan bonds in relation to their biological activity for UTI prevention. The integrity (including authenticity, standardization, efficacy, and safety) of cranberry fruit, juices, and dietary supplements may now be measured by using recent advances in mass spectrometry, liquid chromatography, production of c-PAC standards, and improved simple quantitative techniques.

Relationship between polyphenol content and anti-influenza viral effects of berries.

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Authors
Sekizawa H, Ikuta K, Mizuta K, Takechi S, Suzutani T
Journal
J Sci Food Agric 93(9):2239-41
Abstract

BACKGROUND: Berries are known to have many kinds of biological activities. We focused on their antiviral effect, which has not yet been well evaluated.

RESULTS: We compared the anti-influenza viral effects of berries belonging to the genus Vaccinium - 35 species of blueberry (Vaccinium cyanococcus), the Natsuhaze (Vaccinium oldhamii), bilberry (Vaccinium myrtillus) and cranberry (Vaccinium oxycoccos)- with those belonging to the genus Ribes, i.e. blackcurrant (Ribes nigrum). Only Elliott and Legacy among Northern Highbush varieties but many Rabbiteye varieties such as Austin, Baldwin, Brightblue, Festival, T-100 and Tifblue showed anti-influenza viral activity. Natsuhaze, bilberry, cranberry and blackcurrant had high antiviral effects. A relationship was observed between the antiviral effect and total polyphenol content.

CONCLUSIONS: Antiviral effects were found to differ markedly between berry species. Rabbiteye varieties tended to have higher antiviral effects than Northern, Southern and Half Highbush blueberry varieties. We also found that Natsuhaze, which has recently been harvested in Japan as a potential functional food, had an antiviral effect comparable to that of bilberry, cranberry and blackcurrant. There was a positive relationship between antiviral activity and polyphenol content, indicating the possibility that polyphenol is one of the key factors in the antiviral effects of berries. 2012 Society of Chemical Industry.

The longevity effect of cranberry extract in Caenorhabditis elegans is modulated by daf-16 and osr-1.

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Authors
Guha S, Cao M, Kane RM, Savino AM, Zou S, Dong Y
Journal
Age 35(5):1559-74
Abstract

Nutraceuticals are known to have numerous health and disease preventing properties. Recent studies suggest that extracts containing cranberry may have anti-aging benefits. However, little is known about whether and how cranberry by itself promotes longevity and healthspan in any organism. Here we examined the effect of a cranberry only extract on lifespan and healthspan in Caenorhabditis elegans. Supplementation of the diet with cranberry extract (CBE) increased the lifespan in C. elegans in a concentration-dependent manner. Cranberry also increased tolerance of C. elegans to heat shock, but not to oxidative stress or ultraviolet irradiation. In addition, we tested the effect of cranberry on brood size and motility and found that cranberry did not influence these behaviors. Our mechanistic studies indicated that lifespan extension induced by CBE requires the insulin/IGF signaling pathway and DAF-16. We also found that cranberry promotes longevity through osmotic stress resistant-1 (OSR-1) and one of its downstream effectors, UNC-43, but not through SEK-1, a component of the p38 MAP kinase pathway. However, SIR-2.1 and JNK signaling pathways are not required for cranberry to promote longevity. Our findings suggest that cranberry supplementation confers increased longevity and stress resistance in C. elegans through pathways modulated by daf-16 and osr-1. This study reveals the anti-aging property of widely consumed cranberry and elucidates the underpinning mechanisms.