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2020

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Suppression of Helicobacter Pylori Infection by Daily Cranberry Intake: A Double‐Blind, Randomized, Placebo‐Controlled Trial

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Authors
Zhe‐Xuan Li,* Jun‐Ling Ma,* Yang Guo,* Wei‐Dong Liu,† Ming Li,† Lan‐Fu Zhang,† Yang Zhang,* Tong Zhou,* Jing‐Ying Zhang,* Ha‐Er Gao,* Xiao‐Ying Guo,* Dong‐Man Ye,‡ Wen‐Qing Li,* Wei‐Cheng You* and Kai‐Feng Pan*
Journal
JGH doi:10.1111/jgh.15212
Abstract

Background and aim: Dietary strategies that contribute to reducing incidence of Helicobacter pylori infection without negative side effects are highly desirable owing to worldwide bacterial prevalence and carcinogenesis potential. The aim of this study was to determine dosage effect of daily cranberry consumption on H. pylori suppression over time in infected adults to assess the potential of this complementary management strategy in a region with high gastric cancer risk and high prevalence of H. pylori infection. Methods: This double‐blind, randomized, placebo‐controlled trial on 522 H. pylori‐positive adults evaluated dose–response effects of proanthocyanidin‐standardized cranberry juice, cranberry powder, or their placebos on suppression of H. pylori at 2 and 8 weeks by 13C‐urea breath testing and eradication at 45 days post‐intervention. Results: H. pylori‐negative rates in placebo, low‐proanthocyanidin, medium‐ proanthocyanidin, and high‐proanthocyanidin cranberry juice groups at week 2 were 13.24%, 7.58%, 1.49%, and 13.85% and at week 8 were 7.35%, 7.58%, 4.48%, and 20.00%, respectively. Consumption of high‐proanthocyanidin juice twice daily (44 mg proanthocyanidin/240‐mL serving) for 8 weeks resulted in decreased H. pylori infection rate by 20% as compared with other dosages and placebo (P < 0.05). Percentage of H. pylori‐negative participants increased from 2 to 8 weeks in subjects who consumed 44 mg proanthocyanidin/day juice once or twice daily, showing a statistically significant positive trend over time. Encapsulated cranberry powder doses were not significantly effective at either time point. Overall trial compliance was 94.25%. Cranberry juice and powder were well‐tolerated. Conclusions: Twice‐daily consumption of proanthocyanidin‐standardized cranberry juice may help potentiate suppression of H. pylori infection. Trial registration: ChiCTR1800017522, per WHO ICTRP.

A Multicenter, Randomized, Placebo-Controlled Study Evaluating the Efficacy of a Combination of Propolis and Cranberry (Vaccinium macrocarpon) (DUAB) in Preventing Low Urinary Tract Infection Recurrence in Women Complaining of Recurrent Cystitis.

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Authors
Bruyere F; Azzouzi AR; Lavigne JP; Droupy S; Coloby P; Game X; Karsenty G; Issartel B; Ruffion A; Misrai V; Sotto A; Allaert FA.
Journal
Urologia Internationalis. 103(1):41-48
Abstract

OBJECTIVES: The purpose of the study was to compare the efficacy of a product containing cranberry and propolis (DUAB) to placebo for reducing frequency of cystitis in women with recurrent acute cystitis.METHOD: A multicenter, placebo-controlled, randomized study of women aged >18 years with at least 4 episodes of cystitis in the previous 12 months was performed. The number of cystitis episodes over a 6-month follow-up was the primary end point.RESULTS: Forty-two women were included in the cranberry + propolis group, and 43 women were in the placebo group. The mean age was 53 +/- 18 years, with 6.2 +/- 3.6 cystitis episodes in the previous year, with no differences between the 2 groups. The mean number of infections was lower in the propolis + cranberry group (respectively, 2.3 +/- 1.8 vs. 3.1 +/- 1.8). The total number of cystitis episodes in the first 3 months was lower in the propolis + cranberry group (0.7 +/- 1.1 vs. 1.3 +/- 1.1, p = 0.0257) after adjusting for water consumption. The mean time to onset of the first urinary tract infection (UTI) was also significantly longer in the propolis + cranberry group (69.9 +/- 45.8 days vs. 43.3 +/- 45.9, p = 0.0258). Tolerance to the treatments was good and comparable in both groups.CONCLUSIONS: We demonstrate for the first time that cranberry and propolis supplementation significantly reduces the incidence of UTIs during the first 3 months and delays the onset of an episode of cystitis.

Antibiofilm Properties of Triclosan with EDTA or Cranberry as Foley Catheter Lock Solutions.

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Authors
Ayyash M; Shehabi AA; Mahmoud NN; Al-Bakri AG.
Journal
Journal of Applied Microbiology. 127(6):1876-1888
Abstract

AIMS: To investigate the efficiency of triclosan, ethylenediaminetetraacetic acid (EDTA) and cranberry alone or in combinations against Escherichia coli strains as urinary catheter lock solutions to reduce catheter-associated urinary tract infections.METHODS AND RESULTS: Viable counting was used to assess antibiofilm activities for triclosan, EDTA and cranberry alone or in combinations against E. coli strains embedded in biofilm onto all-silicon Foley catheter surface. The results revealed that combination of triclosan (10 mg ml-1 /EDTA 30 mg ml-1 ) when filling the catheter balloon was able to eradicate and prevent biofilm formation among all tested E. coli including the resistant strains, whereas triclosan (8.5 mg ml-1 )/ cranberry (103 mg ml-1 ) combination was a successful catheter lock solution by preventing all tested strains from adhering onto catheter surface when filled via the eye hole.CONCLUSIONS: The combinations of triclosan/EDTA and triclosan/cranberry were significantly effective in eradicating and preventing biofilm formation of the tested E. coli strains on Foley catheters.SIGNIFICANCE AND IMPACT OF THE STUDY: Combinations of triclosan/EDTA and triclosan/cranberry have a promising application as nonantibiotic catheter lock solution.

Comparative Evaluation of the Antimicrobial Effects of Different Mouthrinses against Streptococcus Mutans: An in Vitro Study.

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Authors
Abu-Obaid E; Salama F; Abu-Obaid A; Alanazi F; Salem M; Auda S.
Journal
Journal of Clinical Pediatric Dentistry. 43(6):398-407
Abstract

Purpose: To assess the antimicrobial effects of different natural and semi-natural mouthrinses on isolates of S. mutans obtained from the saliva of Saudi children and reference strains of S mutans (ATCC 25175). Study design: Saliva samples were collected from 20 children. Natural and semi-natural mouthrinses included were herbal mix mouthrinse, cranberry mouthrinse, chlorhexidine digluconate mouthrinse, cranberry extract mixed with chlorhexidine digluconate mouthrinse, chlorhexidine digluconate mouthrinse with alcohol (positive control), and distilled water (negative control). The microbiological examination tests were minimal inhibitory concentration, minimal bactericidal concentration, and zone of inhibition for the saliva isolates of S. mutans while zone of inhibition test only for reference strain of S. mutans. Results: For reference strain in a comparison with the distilled water, the herbal mix, cranberry, cranberry mixed with chlorhexidine, chlorhexidine, and chlorhexidine with alcohol showed significantly increased zones of inhibition by 36.38, 36.25, 26.13, 17.75, and 12.38, respectively. For saliva isolates in a comparison with the distilled water, the herbal mix, cranberry, cranberry mixed with chlorhexidine, chlorhexidine, and chlorhexidine with alcohol showed significantly increased zones of inhibition by 38.00, 34.25, 22.94, 16.50, and 16.44, respectively. Chlorhexidine with alcohol showed significantly lower minimum inhibitory and bactericidal concentration than the other groups. Conclusions: Herbal mix and cranberry mouthrinses could be effective natural alternative to chlorhexidine mouthrinse with or without alcohol in affecting tested parameters.

Cranberries for Women with Recurrent Urinary Tract Infection: a Meta-Analysis.

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Authors
Tambunan, M. P. Rahardjo, H. E.
Journal
Medical Journal of Indonesia; 2019. 28(3):268-275.
Abstract

Background: Cranberries are the most widely used nonantibiotic prophylaxis for recurrent urinary tract infection (rUTI) in women; however, their efficacy still remains uncertain. Hence, this meta-analysis was aimed to assess the effectiveness, safety, and adherence of cranberry as a prophylactic drug for treating rUTI. Methods: Literature search was conducted using PubMed, EBSCO, Science Direct, Scopus, Cochrane, and Google Scholar. Studies were screened for duplication, inclusion and exclusion criteria, and then reviewed by two authors independently. This included all randomized controlled trials of cranberry derivatives versus placebo and antibiotic prophylaxis. Cochrane risk-of-bias assessment tools were used to evaluate the quality of the study. Quantitative analysis was performed using the Review Manager 5.0 software. Results: Nine studies were included. Among 1,542 participants, cranberry consumption reduced incidence of rUTI in women compared with placebo (p=0.02). The subgroup analysis revealed that only cranberry capsules were superior to placebo (relative risk [RR]=0.67, 95% confidence interval [CI]=0.45-0.98), but not for cranberry juice (RR=0.85, 95% CI: 0.7-1.04). Antibiotics had better outcome than cranberry for rUTI (RR=0.83, 95% CI=0.70-0.98). Most of the participants experienced minor adverse events such as rash and gastrointestinal symptoms. There was also a good adherence rate, ranging from 90.3-99% monthly dose. Conclusion: Cranberry, especially cranberry capsule consumption, had a significant effect in reducing the incidence of rUTI compared with placebo, with good adherence rates, and minor adverse events. In contrast, although antibiotic use had a greater efficacy, it was associated with a higher risk of severe adverse events.

Cranberry A-type Proanthocyanidins Selectively Target Acute Myeloid Leukemia Cells

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Authors
Laura M. Bystrom , Daniel P. Bezerra , Hsiao-Ting Hsu , Hongliang Zong , Luis A. Lara-Martínez , Jeanne P. De Leon , Megan Emmanuel , David Méry , Sara Gardenghi , Duane Hassane , Catherine C. Neto , Susanna Cunningham-Rundles , Michael W. Becker , Stefan
Journal
Blood Adv (2019) 3 (21): 3261–3265. https://doi.org/10.1182/bloodadvances.2018026633
Abstract

Most elderly patients affected with acute myeloid leukemia (AML) will relapse and die of their disease even after achieving complete remission, thus emphasizing the urgent need for new therapeutic approaches with minimum toxicity to normal hematopoietic cells. Cranberry (Vaccinium spp.) extracts have exhibited anticancer and chemopreventive properties that have been mostly attributed to A-type proanthocyanidin (A-PAC) compounds. A-PACs, isolated from a commercially available cranberry extract, were evaluated for their effects on leukemia cell lines, primary AML samples, and normal CD34+ cord blood specimens. Our results indicated potent and specific antileukemia activity in vitro. In addition, the antileukemia activity of A-PACs extended to malignant progenitor and stem cell populations, sparing their normal counterparts. The antileukemia effects of A-PACs were also observed in vivo using patient derived xenografts. Surprisingly, we found that the mechanism of cell death was driven by activation of NF-κB. Overall, our data suggest that A-PACs could be used to improve treatments for AML by targeting leukemia stem cells through a potentially novel pathway.

Cranberry Anti-Cancer Compounds and their Uptake and Metabolism: An Updated Review

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Authors
Prasain, Jeevan K.; Grubbs, Clinton; Barnes, Stephen
Journal
Journal of Berry Research, vol. Pre-press, no. Pre-press, pp. 1-10, 2019; DOI: 10.3233/JBR-180370
Abstract

Consumption of cranberry fruits or juice rich in polyphenols is associated with a wide range of potential health benefits. We and others have previously showed that cranberry juice concentrate and its phytochemicals, flavonols, anthocyanins and A-type proanthocyandins, may have potential to be chemopreventive agents. Although a number of cranberry constituents have been implicated in cancer prevention, our understanding about which metabolites are bio-available to reach target sites and thereby elicit cancer chemopreventive properties is still lacking. However, poor plasma bioavailability of cranberry constituents may be overcome by their potential interactions with gut microbiota by providing cancer prevention through induction of compositional and functional modifications of gut microbiota. Well-designed clinical trials evaluating metabolic and gut microbiome changes associated with cranberry consumption would provide useful information about the cancer patient’s response to dietary intervention with cranberry constituents.

Cranberry as a Promising Natural Source of Potential Nutraceuticals with Anticancer Activity.

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Authors
Mantzorou M; Zarros A; Theocharis S; Pavlidou E; Giaginis C.
Journal
Anticancer Agents Med Chem 10.2174/1871520619666190704163301 [doi]
Abstract

Studies have shown that cranberry and its components may exert anticancer properties. The present study aims to critically summarise the existing experimental studies evaluating the potential effects of cranberry on cancer prevention and treatment. PubMed database was searched to identify rele-vant studies. Current in vitro studies have indicated that cranberry and/or its components may act as chemopreventive agents, diminishing the risk for cancer by inhibiting cells oxidation and inflammatory-related processes, while they may also exert chemotherapeutic effects by inhibiting cell proliferation and angiogenesis, inducing cell apoptosis and attenuating the ability of tumour cells to invade and metastasis. Limited in vivo studies have further documented potential anticancer activity. Cranberry could be considered as a conglomeration of potential effective anticancer drug-like compounds.

Cranberry Extracts Promote Growth of Bacteroidaceae and Decrease Abundance of Enterobacteriaceae in A Guman Gut Simulator Model.

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Authors
O'Connor, K. Morrissette, M. Strandwitz, P. Ghiglieri, M. Caboni, M. Liu HaiYan Khoo, C. D'Onofrio, A. Lewis, K.
Journal
PLoS ONE; 2019. 14(11):e0224836.
Abstract

The opportunistic pathogen Escherichia coli, a common member of the human gut microbiota belonging to the Enterobacteriaceae family, is the causative agent of the majority of urinary tract infections (UTIs). The gut microbiota serves as a reservoir for uropathogenic E. coli where they are shed in feces, colonize the periurethral area, and infect the urinary tract. Currently, front line treatment for UTIs consists of oral antibiotics, but the rise of antibiotic resistance is leading to higher rates of recurrence, and antibiotics cause collateral damage to other members of the gut microbiota. It is commonly believed that incorporation of the American cranberry, Vaccinium macrocarpon, into the diet is useful for reducing recurrence of UTIs. We hypothesized such a benefit might be explained by a prebiotic or antimicrobial effect on the gut microbiota. As such, we tested cranberry extracts and whole cranberry powder on a human gut microbiome-derived community in a gut simulator and found that cranberry components broadly modulate the microbiota by reducing the abundance of Enterobacteriaceae and increasing the abundance of Bacteroidaceae. To identify the specific compounds responsible for this, we tested a panel of compounds isolated from cranberries for activity against E. coli, and found that salicylate exhibited antimicrobial activity against both laboratory E. coli and human UTI E. coli isolates. In a gut simulator, salicylate reduced levels of Enterobacteriaceae and elevated Bacteroidaceae in a dose dependent manner.

Cranberry Proanthocyanidins Neutralize the Effects of Aggregatibacter actinomycetemcomitans Leukotoxin

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Authors
Amel Ben Lagha, Amy Howell and Daniel Grenier
Journal
Toxins 2019, 11(11), 662; https://doi.org/10.3390/toxins11110662
Abstract

Aggregatibacter actinomycetemcomitans is a Gram-negative bacterium that has been strongly associated with localized aggressive periodontitis. The capacity of A. actinomycetemcomitans to produce a leukotoxin (LtxA) that activates pyroptosis in macrophages and induces the release of endogenous danger signals is thought to play a key role in the disease process. The aim of the present study was to investigate the effects of cranberry proanthocyanidins (PACs) on gene expression and cytotoxic activities of LtxA. We showed that cranberry PACs dose-dependently attenuate the expression of genes making up the leukotoxin operon, including ltxB and ltxC, in the two strains of A. actinomycetemcomitans tested. Cranberry PACs (≥62.5 µg/mL) protected macrophages against the cytotoxic effect of purified LtxA. Moreover, cranberry PACs reduced caspase-1 activation in LtxA-treated macrophages and consequently decreased the release of both IL-1β and IL-18, which are known as damage-associated molecular patterns (DAMPs) and contribute to the progression of periodontitis by increasing cell migration and osteoclastogenesis. In addition, cranberry PACs reduced the expression of genes encoding the P2X7 receptor and NALP3 (NACHT, LRR and PYD domains-containing protein 3), which play key roles in pore formation and cell death. Lastly, cranberry PACs blocked the binding of LtxA to macrophages and consequently reduced the LtxA-mediated cytotoxicity. In summary, the present study showed that cranberry PACs reduced LtxA gene expression in A. actinomycetemcomitans and neutralized the cytolytic and pro-inflammatory responses of human macrophages treated with LtxA. Given these properties, cranberry PACs may represent promising molecules for prevention and treatment of the aggressive form of periodontitis caused by A. actinomycetemcomitans.