The aim of this work was to profile, by using an HPLC-MS/MS method, cranberry compounds and metabolites found in human urine after ingestion of a highly standardized cranberry extract (Anthocran R). Two different strategies were adopted for the data analysis: a targeted and an untargeted approach. These strategies allowed the identification of 42 analytes including cranberry components, known metabolites and metabolites hitherto unreported in the literature, including six valerolactones/valeric acid derivatives whose presence in urine after cranberry consumption has never been described before. Absolute concentrations of 26 over 42 metabolites were obtained by using pure available standards. Urine collected at different time points after the last dosage of Anthocran R were tested on the reference strain C. albicans SC5314, a biofilm-forming strain. Fractions collected after 12 h were found to significantly reduce the adhesion and biofilm formation compared to the control (p < 0.05). A similar effect was then obtained by using Anthocran TM Phytosome TM, the lecithin formulation containing 1/3 of standardized cranberry extract and formulated to enhance the absorption of the cranberry components. The urinary profile of cranberry components and metabolites in the urine fractions collected at 1 h, 6 h and 12 h after the last capsule intake were then reproduced by using the pure standards at the concentration ranges found in the urine fraction, and tested on C. albicans. Only the mixture mimicking the urinary fraction collected at 12 h and containing as main components, quercetin and 5-(3',4'-dihydroxyphenyl)-gamma-valerolactone was found effective thus confirming the ex-vivo results.

INTRODUCTION: Ecological approaches to dental caries prevention play a key role in attaining long-term control over the disease and maintaining a symbiotic oral microbiome. OBJECTIVES: This study aimed to investigate the microbial ecological effects of 2 interventional dentifrices: a casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) dentifrice and the same dentifrice supplemented with a polyphenol-rich cranberry extract. METHODS: The interventional toothpastes were compared with each other and with an active control fluoride dentifrice in a double-blinded randomized controlled trial. Real-time quantitative polymerase chain reaction (qPCR) analysis was used to determine changes in the bacterial loads of 14 key bacterial species (8 caries associated and 6 health associated) in the dental plaque of trial participants after they used the dentifrices for 5 to 6 wk. RESULTS: From the baseline to the recall visit, significant differences were observed between the treatment groups in the bacterial loads of 2 caries-associated bacterial species (Streptococcus mutans [P < 0.001] and Veillonella parvula [P < 0.001]) and 3 health-associated bacterial species (Corynebacterium durum [P = 0.008], Neisseria flavescens [P = 0.005], and Streptococcus sanguinis [P < 0.001]). Compared to the fluoride control dentifrice, the CPP-ACP dentifrice demonstrated significant differences for S. mutans (P = 0.032), C. durum (P = 0.007), and S. sanguinis (P < 0.001), while combination CPP-ACP-cranberry dentifrice showed significant differences for S. mutans (P < 0.001), V. parvula (P < 0.001), N. flavescens (P = 0.003), and S. sanguinis (P < 0.001). However, no significant differences were observed in the bacterial load comparisons between the CPP-ACP and combination dentifrices for any of the targeted bacterial species (P > 0.05). CONCLUSIONS: Overall, the results indicate that dentifrices containing CPP-ACP and polyphenol-rich cranberry extracts can influence a species-level shift in the ecology of the oral microbiome, resulting in a microbial community less associated with dental caries (Australian New Zealand Clinical Trial Registry ANZCTR 12618000095268). KNOWLEDGE TRANSFER STATEMENT: The results of this randomized controlled trial indicate that dentifrices containing casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) and polyphenol-rich cranberry extracts were able to beneficially modulate the microbial ecology of dental plaque in a group of high caries-risk patients. This could contribute toward lowering the risk of developing new caries lesions, an important goal sought by patients, clinicians, and policy makers.

Lipid metabolism and inflammation contribute to CVD development. This study investigated whether the consumption of cranberries (CR; Vaccinium macrocarpon) can alter HDL metabolism and prevent inflammation in mice expressing human apo A-I transgene (hApoAITg), which have similar HDL profiles to those of humans. Male hApoAITg mice were fed a modified American Institute of Nutrition-93M high-fat/high-cholesterol diet (16 % fat, 0.25 % cholesterol, w/w; n 15) or the high-fat/high-cholesterol diet containing CR (5 % dried CR powder, w/w, n 16) for 8 weeks. There were no significant differences in body weight between the groups. Serum total cholesterol, non-HDL-cholesterol and TAG concentrations were significantly lower in the control than CR group with no significant differences in serum HDL-cholesterol and apoA-I. Mice fed CR showed significantly lower serum lecithin-cholesterol acyltransferase activity than the control. Liver weight and steatosis were not significantly different between the groups, but hepatic expression of genes involved in cholesterol metabolism was significantly lower in the CR group. In the epididymal white adipose tissue (eWAT), the CR group showed higher weights with decreased expression of genes for lipogenesis and fatty acid oxidation. The mRNA abundance of F4/80, a macrophage marker and the numbers of crown-like structures were less in the CR group. In the soleus muscle, the CR group also demonstrated higher expression of genes for fatty acid beta-oxidation and mitochondrial biogenesis than those of the control. In conclusion, although CR consumption elicited minor effects on HDL metabolism, it prevented obesity-induced inflammation in eWAT with concomitant alterations in soleus muscle energy metabolism.

Anticancer effects were evaluated on three HPLC fractions obtained from a concentrated cranberry juice and cell wall constituents extracted from a probiotic biomass containing Lactobacillus acidophilus CL1285, Lactobacillus casei LBC80R, and Lactobacillus rhamnosus CLR2. The samples were tested at increasing concentrations for the antiproliferative assay using HT-29 cells' line and for the quinone reductase (QR) assay using Hepa-1c1c7 murine hepatoma cells. Fraction 1 (F1) which is highly concentrated with phenolic acids inhibited the growth of the HT-29 cells' line with IC50 values of 14.80 micro g Gallic acid equivalent (GAE)/ml. The fraction 3 (F3) which is highly concentrated in flavonols had potency as QR inducer. Furthermore, the results showed that all cranberry fractions combined with cell wall constituents extracted from the probiotic biomass were more effective in inhibiting the growth of HT-29 as compared to the cranberry fractions tested alone, indicating a possible synergy effect between these bio-functional compounds..

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.

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.

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.

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.

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.

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.