Background: Previous studies indicate cardiovascular health benefits of cranberry juice consumption. However, whether daily consumption of whole cranberries will have sustained vascular benefits in healthy individuals is currently unknown. Objective: To investigate the vascular effects of acute and daily consumption of freeze dried whole cranberry in healthy men and how effects relate to circulating cranberry (poly)phenol metabolites. Methods: A double-blind, parallel-group, randomized controlled trial was conducted in 45 healthy male adults randomly allocated to 1 month daily consumption of either cranberry (9 g powder solubilized in water equivalent to 100 g of fresh cranberries, 525 mg total (poly)phenols) or control (9 g powder, no (poly)phenols). Flow-mediated dilation (FMD, primary outcome), pulse wave velocity (PWV), aortic augmentation index (AIx), blood pressure, heart rate, blood lipids, and blood glucose were assessed at baseline and at 2 h on day 1 and after 1 month. Plasma and 24 h-urine were analyzed before and after treatment using targeted quantitative LC-MS methods including 137 (poly)phenol metabolites. Results: Cranberry consumption significantly increased FMD at 2 h and 1-month (1.1% (95% CI: 1.1%, 1.8%); p(treatment) <= 0.001; p(treatment x time) = 0.606) but not PWV, AIx, blood pressure, heart rate, blood lipids, and glucose. Of the 56 and 74 (poly)phenol metabolites quantified in plasma and urine, 13 plasma and 13 urinary metabolites significantly increased 2 h post-consumption and on day 1, respectively, while 4 plasma and 13 urinary metabolites were significantly higher after 1-month of cranberry consumption, in comparison with control. A multi-variable stepwise linear regression analysis showed that plasma cinnamic acid-4 '-glucuronide, 4-hydroxybenzoic acid-3-sulfate, 2,5-dihydroxybenzoic acid, 3 '-hydroxycinnamic acid, and 5-O-caffeoylquinic acid were significant independent predictors of 2 h FMD effects (R-2 = 0.71), while 3 '-hydroxycinnamic acid, 4-methoxycinnamic acid-3 '-glucuronide, 3-(4 '-methoxyphenyl)propanoic acid 3 '-sulfate, and 3-(4 '-methoxyphenyl)propanoic acid 3 '-glucuronide predicted the 1-month FMD effects (R-2 = 0.52). Conclusions: Acute and daily consumption of whole cranberry powder for 1 month improves vascular function in healthy men and this is linked with specific metabolite profiles in plasma. The National Institutes of Health (NIH)-randomized trial records held on the NIH ClinicalTrials.gov website (NCT02764749). https://clinicaltrials.gov/ct2/show/NCT02764749

Diet and salivary proteins influence the composition of the oral microbiome, and recent data suggest that TAS2R38 bitter taste genetics may also play a role. We investigated the effects of daily exposure to a cranberry polyphenol oral rinse on taste perception, salivary proteins, and oral microbiota. 6-n-Propylthiouracil (PROP) super-tasters (ST, n = 10) and non-tasters (NT, n = 10) rinsed with 30 mL of 0.75 g/L cranberry polyphenol extract (CPE) in spring water, twice daily for 11 days while consuming their habitual diets. The 16S rRNA gene sequencing showed that the NT oral microbiome composition was different than that of STs at baseline (p = 0.012) but not after the intervention (p = 0.525). Principal coordinates analysis using unweighted UniFrac distance showed that CPE modified microbiome composition in NTs (p = 0.023) but not in STs (p = 0.096). The intervention also altered specific salivary protein levels (alpha-amylase, MUC-5B, and selected S-type Cystatins) with no changes in sensory perception. Correlation networks between oral microbiota, salivary proteins, and sensory ratings showed that the ST microbiome had a more complex relationship with salivary proteins, particularly proline-rich proteins, than that in NTs. These findings show that CPE modulated the oral microbiome of NTs to be similar to that of STs, which could have implications for oral health.

Cranberries are used in the production of medicinal preparations and food supplements, which highlights the importance of triterpene compounds determination in cranberry fruit raw material. The aim of our study was to develop and validate for routine testing suitable UPLC-DAD methodology for the evaluation of triterpene acids, neutral triterpenoids, phytosterols, and squalene content in cranberry samples. The developed and optimized UPLC-DAD methodology was validated according to the guidelines of the International Council for Harmonization (ICH), evaluating the following parameters: range, specificity, linearity (R-2 > 0.999), precision, LOD (0.27-1.86 mu g/mL), LOQ (0.90-6.18 mu g/mL), and recovery (80-110%). The developed and validated technique was used for the evaluation of triterpenic compounds in samples of Vaccinium macrocarpon and Vaccinium oxycoccos fruits, and their peels, pulp and seeds. The studied chromatogram profiles of Vaccinium macrocarpon and Vaccinium oxycoccos were identical but differed in the areas of the analytical peaks. Ursolic acid was the dominant compound in fruit samples of Vaccinium macrocarpon and Vaccinium oxycoccos. The highest amounts of triterpenic compounds were detected in the cranberry peels samples. The developed method for the detection of triterpene compounds can be applied in further studies for routine testing on the qualitative and quantitative composition of fruit samples of Vaccinium macrocarpon and Vaccinium oxycoccos species and cultivars.

Phenolic compounds in the fruit of American cranberry (Vaccinium macrocarpon Aiton) determine the antioxidant, anti-inflammatory, anticancer, and other biological effects. The berries are used in the production of medicinal preparations and food supplements, which highlights the importance of qualitative and quantitative analysis of phenolic compounds in cranberry fruit raw material. The aim of our study was to develop and validate an efficient, cost-effective, reproducible, and fast UPLC-DAD methodology for the evaluation of the qualitative and quantitative composition of phenolic compounds in raw material and preparations of American cranberry fruit. During the development of the methodology, chlorogenic acid and the following flavonols were identified in cranberry fruit samples: myricetin-3-galactoside, quercetin-3-galactoside, quercetin-3-glucoside, quercetin-3-a-L-arabinopyranoside, quercetin-3-a-L-arabinofuranoside, quercetin-3-rhamnoside, myricetin, and quercetin. The developed and optimized UPLC-DAD methodology was validated according to the guidelines of the International Council for Harmonization (ICH), evaluating the following parameters: range, specificity, linearity (R2 > 0.999), precision (%RSD < 2%), LOD (0.38-1.01 micro g/mL), LOQ (0.54-3.06 micro g/mL), and recovery (80-110%). The developed methodology was applied to evaluate the qualitative and quantitative composition of phenolic compounds in fruit samples of cranberry cultivars 'Baifay', 'Bergman', 'Prolific', and 'Searles', as well as 'Bain-MC' and 'BL-12' clones. In the tested samples, the majority (about 70%) of the identified flavonols were quercetin derivatives. The greatest amount of quercetin-3-galactoside (1035.35 +or- 4.26 micro g/g DW) was found in fruit samples of the 'Searles' cultivar, and the greatest amount of myricetin-3-galactoside (940.06 +or- 24.91 micro g/g DW) was detected in fruit samples of the 'Woolman' cultivar

A number of clinical trials support the use of standardized cranberry supplement products for prevention of urinary tract infections; however, products that are not well-characterized for sufficient levels of bioactive components may contribute to negative clinical outcomes. Cranberry supplements for consumer use are not regulated and can be formulated different ways using cranberry juice, pomace or various combinations. This can lead to consumer confusion regarding effectiveness of individual products. The current study compared two commercial supplement products, one made from cranberry juice extract and the other from a blend of whole cranberry. The influence of formulation and proanthocyanidin (PAC) solubility on in vitro and ex vivo P-fimbriated Escherichia coli bacterial anti-adhesion activity (AAA) was determined. Both supplement products as well as whole, frozen cranberries were chromatographically separated into crude polyphenolic, sugar and acid fractions. In vitro AAA testing of all fractions confirmed that only those containing soluble PACs elicited activity. The cranberry juice extract product had higher soluble PAC content than the whole cranberry blended product, which contained mainly insoluble PACs. The influence of soluble and insoluble PAC levels in each product on the urinary (ex vivo) AAA was determined following ingestion. The juice extract product was associated with significantly higher urinary AAA than that of the whole berry blended product when consumed once daily over the 1-week intervention period.

Background and Objective: Cholestasis is a liver disease that occurs when bile flow is restricted or blocked. Estrogen-induced cholestasis is marked by a reduction in bile flow and the accumulation of bile acids in the liver as well as liver damage. The aim was to evaluate the hepatoprotective effect on EE-induced cholestasis in rats of Cranberry Water Extract (CWE). Materials and Methods: Adult albino rats weighing approximately 150+or-10 g were divided into six groups of six animals each. As control groups, three groups (I, II and IV) and three experimental groups were used (III, V, VI). Results: Oral administration for 15 days of CWE (150 mg kg- 1 b.wt.) in EE-treated rats (100 g kg- 1 5 days b.wt.) improved serum cholesterol, bile acid and TBIL as well as hepatic SOD and GPx significantly. Also, CWE inhibited ALP, ALT, P-GT activity as well as levels of TNF-a, NO, MMP-2 and MMP-9 and MDA in comparison with the EE treatment rats. On the other hand, the liver TLR4, NF-B and p38MAPK gene expression was down regulated group of rats administrated with cranberry extract when compared with the EE-treated rats. CWE's prophylactic action II is more pronounced than prophylactic one. The hepatoprotective effects of cranberry in restoring normal liver functional ability were also supported by histopathological examination of liver tissues. Conclusion: The results show clearly that cranberry extract has a strong prophylactic effect in EE-induced cholestasis by normalizing the levels of TLR4, NF-B and p38MAPK gene expression.

Background & aims: Patients with Chronic Kidney Disease (CKD) have an imbalance in the gut microbiota that can lead to increase levels of lipopolysaccharides (LPS) and uremic toxins such as indoxyl sulfate (IS), p-cresyl sulfate (p-CS), and indole-3 acetic acid (IAA). Among the therapeutic options for modulating gut microbiota are the bioactive compounds such as polyphenols present in cranberry, fruit with potential antioxidant and anti-inflammatory effects. This clinical trial focuses on evaluating the effects of supplementation with a dry extract of cranberry on plasma levels of LPS and uremic toxins in non-dialysis CKD patients. Methods: It was a randomized, double-blind, placebo-controlled study. Patients were randomized into two groups: the cranberry group received 500 mg of dry cranberry extract (2 times daily), and the placebo group received 500 mg of corn starch (2 times daily) for two months. LPS plasma levels were evaluated by enzyme-linked immunosorbent assay (ELISA) and uremic toxins (IS, p-CS, and IAA) by high-performance liquid chromatography-fluorescence detection. Anthropometric measurements and food intake using the 24-h food recall technique were also evaluated before and after the intervention. Results: Twenty-five participants completed two months of supplementation: 12 patients in the cranberry group (8 women, 56.7 +or- 7.5 years, estimated glomerular filtration rate (eGFR) of 39.2 +or- 21.9 mL/min); 13 patients in the placebo group (9 women, 58.8 +or- 5.1 years, eGFR of 39.7 +or- 12.9 mL/min). As expected, there was a negative association between glomerular filtration rate and p-CS and IS plasma levels at the baseline. No change was observed in the uremic toxins and LPS levels. Conclusion: Cranberry dry extract supplementation for two months did not reduce the LPS and uremic toxins plasma levels produced by the gut microbiota in non-dialysis CKD patients.

Vaccinium macrocarpon (cranberry) is a fruit that has an inhibitory effect on matrix metalloproteinases (MMPs) present in dentin and saliva. The inhibition of MMPs has been shown to prevent dentin erosion. The aim of this study was to analyze the effect of cranberry juice on the reduction of dentin erosion in vitro. Specimens of bovine dentin (4x4x2 mm) were randomized and divided into 4 groups (n = 17/group): distilled water (C-control, pH 7.2); green tea extract solution containing 400 microm epigallo-catechin-gallate (EGCg, positive control, pH 4.5); 10% cranberry extract (CrE, pH 3.9), and cranberry juice (CrJ, Cranberry JuxxTM, pH 2.8). Specimens were submitted to erosive pH cycles for 5 days. Each day, four demineralizations were carried out with 0.1% citric acid (90 s). After the acid challenges, specimens were rinsed and kept in treatment solutions for 1 min; afterwards, they were rinsed and stored in artificial saliva for 1 h at 37degreeC (or overnight at the end of each day). After the experimental period of 5 days, dentin loss was evaluated by contact profilometry. Data were analyzed by ANOVA and Tukey's test (p < 0.05). Dentin loss (microm +/- SD) was significantly lower for all treatments (EGCg = 9.93 +/- 2.90; CrE = 12.10 +/- 5.44; CrJ = 11.04 +/- 5.70) compared to control (21.23 +/- 11.96), but it did not significantly differ from each other. These results indicate that the commercial cranberry juice, despite its low pH, is able to reduce dentin erosion, which might be due to the ability of cranberry components to inhibit MMPs.

Background: Antimicrobial resistance is a rapidly growing global issue affecting the effective treatment of infectious diseases. This provides a window of opportunity for the use and implementation of well researched effective complementary therapies such as herbal medicines. In this literature review, an overview is provided of the effectiveness of herbal medicine to control symptoms of urinary tract in-fections and reduce antibiotic use.Methods: PubMed, CAM-Quest, CORE-Hom, ScienceDirect, CAMBase, Anthromedics.org and AnthroMedLi-brary databases were searched for peer-reviewed meta-analyses, systematic reviews and randomized con-trolled trials from 2005 till 8 October 2020. Included were clinical studies on the use of herbal medicine for clinically diagnosed urinary tract infection with any control group except another herbal medicine. Study quality was assessed using the Joanna Briggs Institute critical appraisal tools.Results: Of the 408 citations identified, 23 met the inclusion criteria: 5 meta-analyses, 3 systematic re-views and 15 randomized controlled trials. Of these studies 13 involved the use of cranberry products, 4 studies concerned traditional Chinese herbal medicines, and 6 studies dealt with other herbal medicines.Conclusions: The latest published meta-analysis including 28 trials reports a clear benefit of Cranberry products for the prevention of recurrent UTIs in women. Five TCM formulas were found to be equally or more effective than antibiotics in the treatment of UTIs. Furthermore, Rosa canina seems to have the potential to prevent UTI in women undergoing a caesarean section. 'Acidif Plus Tablets' as well as 'Canephron' seem to be promising candidates for treating women with uncomplicated recurrent UTI.(c) 2022 Korea Institute of Oriental Medicine. Published by Elsevier B.V.This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )

Aim: Cranberries (Vaccinium macrocarpon) are traditionally used in prevention of urinary tract infections (UTIs). The authors' aim was to evaluate effects of a supplement containing cranberry extract, pumpkin seed extract, vitamin C, and vitamin B-2 on recurrent uncomplicated UTIs in women and their intestinal microbiota.Methods: A prospective, uncontrolled exploratory study was conducted in women with recurrent uncomplicated UTIs. The primary exploratory outcome was the number of UTIs in a 6-month prospective observation period compared with a 6-month retrospective period. Further outcomes included number of antibiotics, quality of life (SF-36), intestinal microbiota (assessed by 16S rRNA amplicon sequencing), and evaluation questions. Parameters were assessed at baseline and after 1, 2, and 7 months (start of intake of cranberry supplement after 1 month for 6 months). p-Values were calculated with the pairwise Wilcoxon signed-rank test for alpha diversity and permutational multivariate analysis of variance.Results: Twenty-three women (aged 52.7 +/- 12.4 years) were included in the study. Participants reported 2.2 +/- 0.8 UTIs (at baseline) in the previous 6 months. After 6 months of cranberry intake, participants reported a significant decrease to 0.5 +/- 0.9 UTIs (p < 0.001). Number of antibiotic therapies was also significantly (p < 0.001) reduced by 68% during 6 months of cranberry intake (0.14 +/- 0.35) when compared with 6 months retrospectively (1.14 +/- 0.71). The SF-36 physical component score increased from 44.9 +/- 5.5 at baseline to 45.7 +/- 4.6 at 7 months (p = 0.16). The SF-36 mental component score decreased slightly from the baseline value of 46.5 +/- 6.5 to 46.2 +/- 6.4 at 7 months (p = 0.74). No significant intragroup mean changes at genus, family, or species level for alpha and beta diversity within the intestinal microbiota were found. In the evaluation questions, participants rated the cranberry extract positively and considered it beneficial. The supplement intake was safe.Conclusions: This study shows that women with recurrent uncomplicated UTIs benefit from cranberry intake. Future larger clinical studies with further investigation of the mechanisms of action are required to determine the effects of cranberries on participants with uncomplicated UTIs.