Consumption of cranberries is associated with the putative effects of preventing urinary tract infections (UTIs). Cranberry proanthocyanidins (PAC) contain unusual double A-type linkages, which are associated with strong interactions with surface virulence factors found on UTI-causing bacteria such as extra-intestinal pathogenic Escherichia coli (ExPEC), depicting in bacterial agglutination processes. In this work, we demonstrated the efficacy of cranberry PAC (200 mug/mL) to agglutinate ExPEC (5.0 x 108 CFU/mL) in vitro as a selective interaction for the design of functionalized biosensors for potential detection of UTIs. We fabricated functionalized screen-printed electrodes (SPEs) by modifying with PAC-polyaniline (PANI) nanocomposites and tested the effectiveness of the PAC-PANI/SPE biosensor for detecting the presence of ExPEC in aqueous suspensions. Results indicated that the PAC-PANI/SPE was highly sensitive (limit of quantification of 1 CFU/mL of ExPEC), and its response was linear over the concentration range of 1-70,000 CFU/mL, suggesting cranberry PAC-functionalized biosensors are an innovative alternative for the detection and diagnosis of ExPEC-associated UTIs. The biosensor was also highly selective, reproducible, and stable.

The emergence and spread of extended-spectrum beta-lactamases (ESBLs), metallo-beta-lactamases (MBLs), or variant low-affinity penicillin-binding proteins (PBPs) pose a major threat to our ability to treat bacterial infection using beta-lactam antibiotics. Although combinations of beta-lactamase inhibitors with beta-lactam agents have been clinically successful, there are no MBL inhibitors in current therapeutic use. Furthermore, recent clinical use of new-generation cephalosporins targeting PBP2a, an altered PBP, has led to the emergence of resistance to these antimicrobial agents. Previous work shows that natural polyphenols such as cranberry-extracted proanthocyanidins (cPAC) can potentiate non-beta-lactam antibiotics against Gram-negative bacteria. This study extends beyond previous work by investigating the in vitro effect of cPAC in overcoming ESBL-, MBL-, and PBP2a-mediated beta-lactam resistance. The results show that cPAC exhibit variable potentiation of different beta-lactams against beta-lactam-resistant Enterobacteriaceae clinical isolates as well as ESBL- and MBL-producing E. coli. We also discovered that cPAC have broad-spectrum inhibitory properties in vitro on the activity of different classes of beta-lactamases, including CTX-M3 ESBL and IMP-1 MBL. Furthermore, we observe that cPAC selectively potentiate oxacillin and carbenicillin against methicillin-resistant but not methicillin-sensitive staphylococci, suggesting that cPAC also interfere with PBP2a-mediated resistance. This study motivates the need for future work to identify the most bioactive compounds in cPAC and to evaluate their antibiotic-potentiating efficacy in vivo.

Cranberry (Vaccinium macrocarpon) may be a potent natural adjuvant for the prevention of oral diseases due to its anti-adherence, anti-cariogenic, and anti-inflammatory properties. However, the high titrable acidity of cranberry juice (CJ) has been reported to cause gastrointestinal discomfort, leading consumers to restrict their intake of this beverage. Electrodialysis with a bipolar membrane (EDBM) can reduce the organic acid content of CJ while retaining the flavonoids associated with potential health benefits. This study aimed to assess how the deacidification of CJ by EDBM impacts the antibacterial properties of the beverage against cariogenic (Streptococcus mutans, Streptococcus sobrinus) and commensal (Streptococcus gordonii, Streptococcus oralis, Streptococcus salivarius) streptococci, and how it affects oral epithelial barrier function and inflammatory response in an in vitro model. The removal of organic acids from CJ (deacidification rate 42%) reduced the bactericidal activity of the beverage against planktonic S. mutans and S. gordonii after a 15-min exposure, whereas only the viability of S. gordonii was significantly impacted by CJ deacidification rate when the bacteria were embedded in a biofilm. Moreover, conditioning saliva-coated hydroxyapatite with undiluted CJ samples significantly lowered the adherence of S. mutans, S. sobrinus, and S. oralis. With respect to epithelial barrier function, exposure to CJ deacidified at a rate of 19% maintained the integrity of a keratinocyte monolayer over the course of 24 h compared to raw CJ, as assessed by the determination of transepithelial electrical resistance (TER) and fluorescein isothiocyanate-conjugated dextran paracellular transport. These results can be in part attributed to the inability of the deacidified CJ to disrupt two tight junction proteins, zonula occludens-1 and occludin, following exposure, unlike raw CJ. Deacidification of CJ impacted the secretion of IL-6, but not of IL-8, by oral epithelial cells. In conclusion, deacidification of CJ appears to provide benefits with respect to the maintenance of oral health.

The ability of Streptococcus mutans to adhere to oral surfaces and form biofilm is a key step in the tooth decay process. The aim of this study was to investigate a berry (wild blueberry, cranberry, and strawberry) polyphenolic fraction, commercialized as OrophenolR, for its antibacterial, anti-biofilm, and anti-adhesion properties on S. mutans. Moreover, the biocompatibility of the fraction with human oral epithelial cells was assessed. Phenolic acids, flavonoids (flavonols, anthocyanins, flavan-3-ols), and procyanidins made up 10.71%, 19.76%, and 5.29% of the berry polyphenolic fraction, respectively, as determined by chromatography and mass spectrometry. The berry polyphenolic preparation dose-dependently inhibited S. mutans biofilm formation while not reducing bacterial growth. At concentrations ranging from 250 to 1000 micro g/mL, the fraction inhibited the adhesion of S. mutans to both saliva-coated hydroxyapatite and saliva-coated nickel-chrome alloy. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis showed that incubating S. mutans with the berry polyphenolic fraction was associated with a reduced expression of luxS gene, which regulates quorum sensing in S. mutans. The berry fraction did not show any significant cytotoxicity in an oral epithelial cell model. In conclusion, OrophenolR, which is a mixture of polyphenols from wild blueberry, cranberry and strawberry, possesses interesting anti-caries properties while being compatible with oral epithelial cells.

Cranberries are widely recognized as a functional food that can promote oral health. However, the high concentration of organic acids in cranberry juice can cause tooth enamel erosion. Electrodialysis with bipolar membrane (EDBM) is a process used for the deacidification of cranberry juice. The present study investigated whether the removal of organic acids (0%, 19%, 42%, 60%, and 79%) from cranberry juice by EDBM affects its antibacterial activity against major periodontopathogens as well as its anti-inflammatory properties in an oral epithelial cell model. A deacidification rate 60% attenuated the bactericidal effect against planktonic and biofilm-embedded Aggregatibacter actinomycetemcomitans but had no impact on Porphyromonas gingivalis and Fusobacterium nucleatum. Cranberry juice increased the adherence of A. actinomycetemcomitans and P. gingivalis to oral epithelial cells, but reduced the adherence of F. nucleatum by half regardless of the deacidification rate. F. nucleatum produced more hydrogen sulfide when it was exposed to deacidified cranberry juice with a deacidification rate 42% compared to the raw beverage. Interestingly, the removal of organic acids from cranberry juice lowered the cytotoxicity of the beverage for oral epithelial cells. Deacidification attenuated the anti-inflammatory effect of cranberry juice in an in vitro oral epithelial cell model. The secretion of IL-6 by lipopolysaccharide (LPS)-stimulated oral epithelial cells exposed to cranberry juice increased proportionally with the deacidification rate. No such effect was observed with respect to the production of IL-8. This study provided evidence that organic acids, just like phenolic compounds, might contribute to the health benefits of cranberry juice against periodontitis.

Background We aimed to evaluate the effect of cranberry supplementation on serum liver enzymes, hepatic steatosis, and cardiometabolic risk factors in patients with non-alcoholic fatty liver (NAFLD). Methods In the present parallel-designed randomized controlled clinical trial, 110 patients with NAFLD were enrolled. The patients were randomized to receive 144 mg cranberry capsule or placebo for 6 months. The primary efficacy of the treatment was lipid profile, glycemic measurements, and liver enzyme levels. Results The data were reported for 46 in the supplementation group and 48 in the placebo group. The patient's mean (SD) age was 43.16 (11.08) years. No significant differences between groups were observed regarding the post-intervention level of liver enzyme. The mean after-intervention levels of total cholesterol (p < 0.001) and triglyceride (p = 0.01) were significantly lower in the intervention group compared with the placebo group. At the end of the study, the mean insulin and HOMA-IR levels were significantly lower in the cranberry group compared with the placebo group. Significantly more patients in the cranberry group experienced a decrease in steatosis level compared with the control group. Conclusion The results of the present study showed that cranberry supplementation had a positive effect on some lipid profiles, insulin resistance, and hepatic steatosis in patients with NAFLD.

Purpose: This review aims to compare the magnitude of the effects of chronic consumption of fruits; specifically berries, citrus and cherries on cardiovascular disease (CVD) risk factors. Methods: PubMed, Web of Science, Scopus, and psycARTICLES were searched from inception until January 2020. Forty-five chronic ( 1 week) randomised controlled trials assessing CVD risk factors including endothelial (dys)function, blood pressure (BP), blood lipids and inflammatory biomarkers were included. Results: Investigated interventions reported improvements in endothelial function (n = 8), inflammatory biomarkers and lipid status (n = 14), and BP (n = 10). Berries including juice of barberry, cranberry, grape, pomegranate, powder of blueberry, grape, raspberry and freeze-dried strawberry significantly reduced SBP by 3.68 mmHg (95% CI - 6.79 to - 0.58; P= 0.02) and DBP by 1.52 mmHg (95% CI - 2.87 to - 0.18, P = 0.04). In subgroup analysis, these associations were limited to cranberry juice (SBP by 1.52 mmHg [95% CI - 2.97 to - 0.07); P = 0.05], DBP by 1.78 mmHg [95% CI - 3.43 to - 0.12, P = 0.04] and cherry juice (SBP by 3.11 mmHg [95% CI - 4.06 to - 2.15; P = 0.02]). Berries also significantly elevated sVCAM-1 levels by 14.57 ng/mL (85% CI 4.22 to 24.93; P = 0.02). Conclusion: These findings suggest that supplementing cranberry or cherry juice might contribute to an improvement in blood pressure. No other significant improvements were observed for other specified fruits. More research is warranted comparing different classes of fruit and exploring the importance of fruit processing on their cardiovascular-protective effects.

Purpose: The purpose of this paper with meta-analysis is to clarify the effects of cranberry consumption on features of the metabolic syndrome of interest of all relevant randomized controlled trials (RCTs). Design/methodology/approach: A systematic literature search was conducted on ISI web of science, PubMed, Embase, the Cochrane library and Google Scholar databases, to include trials published up to March 2019. Weighted mean differences (WMD) were calculated from a random or fixed-effects models. Between-study heterogeneity was assessed by Cochrane's test and I2 index. Findings: Ten RCTs were included in this review which involving a total of 371 subjects. Our meta-analysis showed that cranberry consumption had beneficial effects on waist circumference (WMD -0.49, 95% CI -0.96 to -0.036; p = 0.034). No significant effect of cranberry consumption on fasting blood glucose, high-density lipoprotein cholesterol, triglycerides and blood pressure was found in this meta-analysis. Originality/value: To the best of the authors' knowledge, this is the first systematic review with meta-analysis of RCTs that investigate the effect of cranberry consumption on features of the metabolic syndrome.

Purpose – The purpose of this paper with meta-analysis is to clarify the effects of cranberry consumption on features of the metabolic syndrome of interest of all relevant randomized controlled trials (RCTs). Design/methodology/approach – A systematic literature search was conducted on ISI web of science, PubMed, Embase, the Cochrane library and Google Scholar databases, to include trials published up to March 2019. Weighted mean differences (WMD) were calculated from a random or fixed-effects models. Between-study heterogeneity was assessed by Cochrane’s test and I2 index.Findings – Ten RCTs were included in this review which involving a total of 371 subjects. Our meta-analysis showed that cranberry consumption had beneficial effects on waist circumference (WMD 0.49,95% CI 0.96 to 0.036; p = 0.034). No significant effect of cranberry consumption on fasting blood glucose,high-density lipoprotein cholesterol, triglycerides and blood pressure was found in this meta-analysis.Originality/value – To the best of the authors’ knowledge, this is the first systematic review with meta-analysis of RCTs that investigate the effect of cranberry consumption on features of the metabolic syndrome.

Emerging cardiovascular disease (CVD) risk factors, including central vascular function and HDL efflux, may be modifiable with food-based interventions such as cranberry juice. A randomized, placebo-controlled, crossover trial was conducted in middle-aged adults with overweight/obesity (n = 40; mean BMI: 28.7 +or- 0.8 kg/m2; mean age: 47 +or- 2 years) and elevated brachial blood pressure (mean systolic/diastolic BP: 124 +or- 2/81 +or- 1 mm Hg). Study participants consumed 500 mL/d of cranberry juice (~16 fl oz; 27% cranberry juice) or a matched placebo juice in a randomized order (8-week supplementation periods; 8-week compliance break), with blood samples and vascular measurements obtained at study entry and following each supplementation period. There was no significant treatment effect of cranberry juice supplementation on the primary endpoint of central systolic blood pressure or central or brachial diastolic pressure. Cranberry juice significantly reduced 24-h diastolic ambulatory BP by ~2 mm Hg compared to the placebo (p = 0.05) during daytime hours. Cranberry juice supplementation did not alter LDL-C but significantly changed the composition of the lipoprotein profile compared to the placebo, increasing the concentration of large LDL-C particles (+29.5 vs. -6.7 nmol/L; p = 0.02) and LDL size (+0.073 vs. -0.068 nm; p = 0.001). There was no effect of treatment on ex vivo HDL efflux in the total population, but exploratory subgroup analyses identified an interaction between BMI and global HDL efflux (p = 0.02), with greater effect of cranberry juice in participants who were overweight. Exploratory analyses indicate that baseline C-reactive protein (CRP) values may moderate treatment effects. In this population of adults with elevated blood pressure, cranberry juice supplementation had no significant effect on central systolic blood pressure but did have modest effects on 24-h diastolic ambulatory BP and the lipoprotein profile. Future studies are needed to verify these findings and the results of our exploratory analyses related to baseline health moderators.