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Some New Findings Regarding the Antiadhesive Activity of Cranberry Phenolic Compounds and Their Microbial-Derived Metabolites against Uropathogenic Bacteria.

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Authors
González de Llano D, Liu H, Khoo C, Moreno-Arribas MV, Bartolomé B.
Journal
J Agric Food Chem. 2019 Feb 12. doi: 10.1021/acs.jafc.8b05625
Abstract

Findings concerning the antiadhesive activity of cranberry phenolic compounds and their microbial-derived metabolites against Gram-negative ( Escherichia coli ATCC 53503 and DSM 10791) and Gram-positive ( Enterococcus faecalis 04-1) bacteria in T24 cells are reported. A-Type procyanidins (A2 and cinnamtannin B-1) exhibited antiadhesive activity (at concentrations ≥250 μM), a feature that was not observed for B-type procyanidins (B2). The metabolites hippuric acid and α-hydroxyhippuric acid also showed effective results at concentrations ≥250 μM. With regard to conjugated metabolites, sulfation seemed to increase the antiadhesive activity of cranberry-derived metabolites as 3-(3,4-dihydroxyphenyl)propionic acid 3- O-sulfate presented active results, unlike its corresponding nonsulfated form. In contrast, methylation decreased antiadhesive activity as 3,4-dihydroxyphenylacetic acid was found to be active but not its corresponding methylated form (4-hydroxy-3-methoxyphenylacetic acid). As a whole, this work sustains the antiadhesive activity of cranberry-derived metabolites as one of the mechanisms involved in the beneficial effects of cranberries against urinary tract infections.

Water-Soluble Cranberry Extract Inhibits Vibrio Cholerae Biofilm Formation Possibly Through Modulating the Second Messenger 3',5'-Cyclic Diguanylate Level.

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Authors
Pederson, D. B. Dong YuQing Blue, L. B. Smith, S. V. Cao, M
Journal
PLoS ONE; 2018. 13(11):e0207056.
Abstract

Quorum sensing (QS) and nucleotide-based second messengers are vital signaling systems that regulate bacterial physiology in response to changing environments. Disrupting bacterial signal transduction is a promising direction to combat infectious diseases, and QS and the second messengers are undoubtedly potential targets. In Vibrio cholerae, both QS and the second messenger 3', 5' - cyclic diguanylate (c-di-GMP) play a central role in controlling motility, motile-to-sessile life transition, and virulence. In this study, we found that water-soluble extract from the North American cranberry could significantly inhibit V. cholerae biofilm formation during the development/maturation stage by reducing the biofilm matrix production and secretion. The anti-biofilm effect by water-soluble cranberry extract was possibly through modulating the intracellular c-di-GMP level and was independent of QS and the QS master regulator HapR. Our results suggest an opportunity to explore more functional foods to fight stubborn infections through interference with the bacterial signaling systems.

A Review of Cranberry Use for Preventing Urinary Tract Infections in Older Adults.

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Authors
Luczak T; Swanoski M.
Journal
Consultant Pharmacist. 33(8):450-453,
Abstract

Urinary tract infections (UTIs) are one the of the most common types of infections in adults older than 65 years of age. Preventing UTIs with prophylactic antibiotics increases the risk of side effects and microbial resistance, and is costly. Cranberry fruit and juices contain the compound proanthrocyanidins (PACs), specifically proanthrocyanidin-A, which exerts antiadhesion characteristics against bacteria. Cranberry products therefore have been an attractive, nonantibiotic preventative option for UTIs; however, the current literature supporting cranberry use in older adults is controversial. This could be multifactorial owing to the heterogeneity of the older population as well as inconsistencies in the recommended dose of PAC in the current literature. Evidence supports that cranberry may be beneficial in preventing UTIs in specific populations such as catheterassociated UTI and postradiotherapy prostate cancer. The cost of daily capsules versus the cost of preventing a UTI in older adults is an important consideration for initiating therapy.

A Systematic Review of Non-Antibiotic Measures for the Prevention of Urinary Tract Infections in Pregnancy.

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Authors
Ghouri F; Hollywood A; Ryan K.
Journal
BMC Pregnancy & Childbirth. 18(1):99
Abstract

BACKGROUND: Urinary tract infections (UTIs) are common in pregnancy and account for the highest proportion of primary care antibiotic prescriptions issued to pregnant women in the UK. It is well known that antibiotic use is associated with increased antimicrobial resistance and therefore measures to minimise antibiotic use for UTI prevention have been studied. The efficacy and safety of these measures in pregnancy have not been addressed and therefore the aim of this study was to systematically review the literature to identify and evaluate potential measures to prevent UTIs in pregnant women. METHODS: Ten databases (EMBASE, AMED, BNI, CINAHL, Medline, PubMed, PsycINFO, Cochrane Trials, Scopus and Science Direct) were systematically searched in July 2017 for studies reporting non-antibiotic measures to prevent UTIs in pregnancy. The terms ("urinary tract infection" or UTI or bacteriuria or cystitis) AND (prevention) AND (pregnan*) were used. The quality of the publications was appraised using the Critical Appraisal Skills Programme (CASP) checklists for cohort study, case-control study and randomised controlled trial. The results were synthesised using a textual narrative approach. RESULTS: Search results yielded 3276 publications and after reviewing titles and removing duplicates, 57 full text articles were assessed for eligibility and eight were included in the review. Five different approaches (hygiene measures, cranberry juice, immunisation, ascorbic acid and Canephron N) have been identified, all of which are reported to be safe in pregnancy. CONCLUSION: The quality of the evidence varied considerably and only hygiene measures were supported by evidence to be recommended in practice. Future work needs to concentrate on strengthening the evidence base through improved design and reporting of studies with a focus on immunisation, ascorbic acid and Canephron N.

Advantages of a Validated UPLC-MS/MS Standard Addition Method for the Quantification of A-Type Dimeric and Trimeric Proanthocyanidins in Cranberry Extracts in Comparison with Well-Known Quantification Methods.

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Authors
Dooren, I. van Foubert, K. Theunis, M. Naessens, T. Pieters, L. Apers, S.
Journal
Journal of Pharmaceutical and Biomedical Analysis;148:32-41.
Abstract

The berries of Vaccinium macrocarpon, cranberry, are widely used for the prevention of urinary tract infections. This species contains A-type proanthocyanidins (PACs), which intervene in the initial phase of the development of urinary tract infections by preventing the adherence of Escherichia coli by their P-type fimbriae to uroepithelial cells. Unfortunately, the existing clinical studies used different cranberry preparations, which were poorly standardized. Because of this, the results were hard to compare, which led sometimes to conflicting results. Currently, PACs are quantified using the rather non-specific spectrophotometric 4-dimethylaminocinnamaldehyde (DMAC) method. In addition, a normal phase HPTLC-densitometric method, a HPLC-UV method and three LC-MS/MS methods for quantification of procyanidin A2 were recently published. All these methods contain some shortcomings and errors. Hence, the development and validation of a fast and sensitive standard addition LC-MS/MS method for the simultaneous quantification of A-type dimers and trimers in a cranberry dry extract was carried out. A linear calibration model could be adopted for dimers and, after logarithmic transformation, for trimers. The maximal interday and interconcentration precision was found to be 4.86% and 4.28% for procyanidin A2, and 5.61% and 7.65% for trimeric PACs, which are all acceptable values for an analytical method using LC-MS/MS. In addition, twelve different cranberry extracts were analyzed by means of the newly validated method and other widely used methods. There appeared to be an enormous variation in dimeric and trimeric PAC content. Comparison of these results with LC-MS/MS analysis without standard addition showed the presence of matrix effects for some of the extracts and proved the necessity of standard addition. A comparison of the well-known and widely used DMAC method, the butanol-HCl assay and this newly developed LC-MS/MS method clearly indicated the need for a reliable method able to quantify A-type PACs, which are considered to be the pharmacologically active constituents of cranberry, since neither the DMAC or butanol-HCl assays are capable of distinguishing between A and B-type PACs and therefore cannot detect adulterations with, for example, extracts with a high B-type PAC content. Hence, the combination of the DMAC method or butanol-HCl assay with this more specific LC-MS/MS assay could overcome these shortcomings.

American Cranberries and Health Benefits - An Evolving Story of 25 Years.

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Authors
Zhao S; Liu H; Gu L.
Journal
Journal of the Science of Food & Agriculture. 10.1002/jsfa.8882 [doi]
Abstract

Cranberries contain various types of bioactive components. Scientists have been studying cranberries' beneficial effects on urinary tract health since the 20th century. In the 21st century, the protection provided by cranberry phytochemicals against cancer and vascular diseases has drawn more attention from researchers. Anthocyanins, procyanidins, and flavonols in cranberries were all documented to have potential effects on cancer prevention. The cardiometabolic effects of cranberries have been investigated in several clinical trials. It was found that cranberries positively affect atherosclerotic cholesterol profiles and that they reduced several cardiometabolic risk factors. Nowadays, growing evidence suggests other important roles of cranberries in maintaining digestive health. Cranberry juice or cranberries have been shown to inhibit the colonization of H. pylori in stomach, and protect against intestinal inflammation. For future research, clinical trials with improved study design are urgently needed to demonstrate cranberries' benefits on urinary tract health and cardiometabolic diseases. Hypothesis-driven studies using animals or cell culture are needed to elucidate the mechanisms of cranberries' effects on digestive health.

Anticancer Activity of Chlorhexidine and Cranberry Extract: an In-Vitro Study.

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Authors
Khairnar MR; Wadgave U; Jadhav H; Naik R.
Journal
Journal of Experimental Therapeutics & Oncology. 12(3):201-205
Abstract

Introduction: Oral cancer is considered to be a global pandemic. The study was conducted to assess the anti-cancer activities of Chlorhexidine (CHX) and Cranberry against oral cancer cell lines. Material and Methods: Anticancer activity of CHX and Cranberry extract (CE) was assessed against AW13516 (poorly to moderately differentiated squamous cell carcinoma of tongue) and KB (Nasopharyngeal carcinoma) using Sulforhodamine B (SRB) assay at the Advanced Centre for Treatment Research and Education in Cancer (ACTREC) Mumbai, India. Three dose related parameters GI50, TGI and LC50 were calculated for each drug. Results: CE (80micro g/ml) showed no anti-cancer property against AW13516 cell line; however it showed 70.6% growth inhibition against KB cell line. CHX demonstrated 80.15% & 95.7% of growth inhibition against AW13516 & KB cell line respectively. Both the drugs were less potential than positive control drug Adriamycin, as reflected by their GI50, TGI and LC50 values. Conclusion: CHX exhibited better anti-cancer properties than CE for both the oral cancer cell lines.

Benefits and Risks of Cranberries in Cystitis in Cats and Dogs.

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Authors
Desfontis, J. C. Mallem, Y.
Journal
Point Veterinaire; 49(384 (Part 1)):21.
Abstract

This article describes the chemical composition, efficacy and risks of using cranberries for the treatment of cystitis in cats and dogs.

Chronic Consumption of a Low Calorie, High Polyphenol Cranberry Beverage Attenuates Inflammation and Improves Glucoregulation and HDL Cholesterol in Healthy Overweight Humans: a Randomized Controlled Trial.

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Authors
Chew B; Mathison B; Kimble L; McKay D; Kaspar K; Khoo C; Chen CO; Blumberg J.
Journal
European Journal of Nutrition. 10.1007/s00394-018-1643-z [doi]
Abstract

PURPOSE: We studied the health benefits of low calorie cranberry beverage consumption on glucoregulation, oxidative damage, inflammation, and lipid metabolism in overweight but otherwise healthy humans. METHODS: 78 overweight or obese men and women (30-70 years; BMI 27-35 kg/m2) with abdominal adiposity (waist: hip>0.8 for women and >0.9 for men; waist: height>=0.5) consumed 450 mL placebo or low calorie, high polyphenol cranberry extract beverage (CEB) daily for 8 week in a randomized, double-blind, placebo-controlled, parallel design trial. Blood and urine samples were collected after overnight fast at baseline and after 8 weeks of daily beverage consumption. Blood and urine samples were also collected during 3 oral glucose tolerance test (OGTT) challenges: (1) pre-intervention without the test beverages, (2) following a single dose of placebo or CEB at baseline (week 0), and (3) following a single dose of placebo or CEB at 8 week. RESULTS: Compared to placebo, a single CEB dose at baseline lowered endothelin-1 and elevated nitric oxide and the reduced:oxidized glutathione ratio (P<0.05). Interferon-gamma was elevated (P<0.05) after a single CEB dose at baseline; however, after 8 week of CEB intervention, fasting C-reactive protein was lower (P<0.05). CEB consumption for 8 week also reduced serum insulin and increased HDL cholesterol compared to placebo (P<0.05). CONCLUSIONS: An acute dose of low calorie, high polyphenol cranberry beverage improved antioxidant status, while 8 week daily consumption reduced cardiovascular disease risk factors by improving glucoregulation, downregulating inflammatory biomarkers, and increasing HDL cholesterol.

Consumption of Cranberry Functional Beverage Reduces Gingival Index and Plaque Index in Patients with Gingivitis.

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Authors
Wozniewicz M,Nowaczyk PM, Kurhanska-Flisykowska A, Wyganowska-Swi&#261;tkowska M, Lasik-Kurdys M, Walkowiak J, Bajerska J
Journal
Nutrition Research 58:36-45. https://doi.org/10.1016/j.nutres.2018.06.011
Abstract

Periodontal disease is highly prevalent worldwide, and consumption of certain foods, such as fruits, seem to improve the effectiveness of periodontal therapy (PT) due to their antiadhesive, immunomodulatory, and antioxidative properties. We hypothesized that the cranberry functional beverage (CFB) consumed for eight weeks improves gingival inflammation indices via inhibition of dental plaque, and alterations in antioxidant status, and systemic inflammation in patients with gingivitis. In this two-arm randomized controlled study, fifty participants were divided into an experimental group (CFB), administered daily with 750 ml CFB, or a control group administered the same amount of water. All patients underwent nonsurgical PT prior to the intervention. Gingival (GI) and bleeding on probing (BoP) indices of inflammation, plaque (PI) and approximal plaque (API) indices of dental plaque deposition, saliva and serum total antioxidant status (TAS), serum malonylodialdehyde level (MDA), and interleukin 1-beta level (IL-1beta) were measured pre- and postintervention. A risk of caries development was determined by Streptococcus mutans (SM) and Lactobacillus spp. (LAB) counts in supragingival dental plaque. Changes in GI and PI but not BoP and API were significantly more pronounced in the CFB group compared to the control group. Serum or saliva TAS, IL-1beta, and MDA did not differ between groups. The number of SM reduced in CFB, but not in the control group. We demonstrated that the consumption of CFB improves gingival and plaque indices without posing a risk of caries development. Thus CFB can be recommended as a safe adjunct for nonsurgical PT in patients with gingivitis.