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Development and Validation of the UPLC-DAD Methodology for the Detection of Triterpenoids and Phytosterols in Fruit Samples of Vaccinium macrocarpon Aiton and Vaccinium oxycoccos L.

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Authors
Sedbare, Rima; Raudone, Lina; Zvikas, Vaidotas; Viskelis, Jonas; Liaudanskas, Mindaugas; Janulis, Valdimaras
Journal
MOLECULES 27;14:4403. 10.3390/molecules27144403
Abstract

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.

Development, validation, and application of the UPLC-DAD methodology for the evaluation of the qualitative and quantitative composition of phenolic compounds in the fruit of American cranberry (Vaccinium macrocarpon Aiton).

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Authors
Urbstaite, R., Raudone, L., Liaudanskas, M., Janulis, V.
Journal
Molecules 2022. 27(2).
Abstract

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

 

Differences in urinary bacterial anti-adhesion activity after intake of cranberry dietary supplements with soluble versus insoluble proanthocyanidins.

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Authors
Howell, A. B.; Dreyfus, J. F.; Chughtai, B.
Journal
Journal of Dietary Supplements; 2022. 19(5):621-639.
Abstract

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.

 

Downregulation of TLR4-NF-B-p38 MAPK signalling in cholestatic rats treated with cranberry extract.

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Authors
Fayed, A. M.; Abdalla, E. A.; Hassan, S. A.; Hussein, M. A.; Roshdy, T. M.
Journal
Pakistan Journal of Biological Sciences; 2022. 25(2):112-122.
Abstract

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.

Effect of cranberry supplementation on toxins produced by the gut microbiota in chronic kidney disease patients: a pilot randomized placebo-controlled trial.

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Authors
Teixeira, K. T. R.; Moreira, L. de S. G.; Borges, N. A.; Brum, I.; Paiva, B. R. de; Alvarenga, L.; Nakao, L. S.; Leal, V. de O.; Carraro-Eduardo, J. C.; Rodrigues, S. D.; Lima, J. D.; Ribeiro-Alves, M.; Mafra, D.
Journal
Clinical Nutrition ESPEN; 2022. 47:63-69.
Abstract

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.

Effect of the cranberry ( Vaccinium macrocarpon ) juice on reducing dentin erosion: an in vitro study.

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Authors
Kato MT, Cardoso CAB, Jordao MC, Galvao RPO, Iscuissati AGS, Kinoshita AMO, Buzalaf MAR
Journal
Brazilian Oral Research. 36:e076
Abstract

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.

 

Effectiveness of herbal medicines to prevent and control symptoms of urinary tract infections and to reduce antibiotic use: A literature review

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Authors
van Wietmarschen, Herman; van Steenbergen, Noortje; van der Werf, Esther; Baars, Erik
Journal
INTEGRATIVE MEDICINE RESEARCH 11;4:100892. 10.1016/j.imr.2022.100892
Abstract

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/ )

 

Effects of a Supplement Containing a Cranberry Extract on Recurrent Urinary Tract Infections and Intestinal Microbiota: A Prospective, Uncontrolled Exploratory Study

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Authors
Jeitler, Michael; Michalsen, Andreas; Schwiertz, Andreas; Kessler, Christian S.; Koppold-Liebscher, Daniela; Grasme, Julia; Kandil, Farid I.; Steckhan, Nico
Journal
JOURNAL OF INTEGRATIVE AND COMPLEMENTARY MEDICINE 28;5:399-406. 10.1089/jicm.2021.0300
Abstract

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.

 

Effects of blueberry and cranberry on type 2 diabetes parameters in individuals with or without diabetes: A systematic review and meta-analysis of randomized clinical trials

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Authors
Delpino, Felipe Mendes; Figueiredo, Lilian Munhoz; da Silva, Taiciane Goncalves; Flores, Thayna Ramos
Journal
NUTRITION METABOLISM AND CARDIOVASCULAR DISEASES 32;5:1093-1109. 10.1016/j.numecd.2022.02.004
Abstract

Aims: Blueberry and cranberry are rich in polyphenols that are associated with diabetes reduction. This study aimed: 1) to systematically review the literature on the effects of blueberry and cranberry consumption and type 2 diabetes parameters in individuals with or without type 2 diabetes and 2) to quantify these effects by carrying out a meta-analysis.Data synthesis: A systematic review and meta-analysis were performed using articles present in seven databases (PubMed, LILACS, Scielo, Scopus, Web of Science, Cochrane, and Embase), including publications until May 2021. We included randomized clinical trials that compared blueberry or cranberry effects on type 2 diabetes parameters, such as fasting blood glucose, insulin resistance, and glycated hemoglobin. Quality of the studies was performed using the Cochrane scale, while the Egger test assessed the publication bias and meta-regression the estimated effect sizes with potential moderator variables. From the 2034 studies identified, 39 were read in full and 22 were included in meta-analysis. In individuals with diabetes, the consumption of blueberry or cranberry significantly reduced fasting blood glucose [MD: -17.72 mg/dl; 95% CI: -29.62, -5.82; p = 0.03; 12 = 57%] and glycated hemoglobin [MD: -0.32%; 95% CI: -0.57, -0.07; p = 0.15; 12 = 39%], whereas for insulin resistance the effects were null. Results were not significant for the general population, except in the sensitivity analysis for fasting blood glucose.Conclusions: The consumption of blueberry and cranberry significantly reduced fasting blood glucose and glycated hemoglobin levels in individuals with diabetes, with high credibility of the evidence. (C) 2022 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

Evaluation of Anti-cancer Activities of Cranberries Juice Concentrate in Osteosarcoma Cell Lines (MG-63)

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Authors
Hattiholi, Aishwarya; Tendulkar, Shivani; Kumbar, Vijay; Rao, Malleswara; Kugaji, Manohar; Muddapur, Uday; Bhat, Kishore
Journal
INDIAN JOURNAL OF PHARMACEUTICAL EDUCATION AND RESEARCH 56;4:1141-9. 10.5530/ijper.56.4.195
Abstract

Aim/Background: Osteosarcoma is one of the prevalent cancers occurring mostly in adolescents and has a high risk of malignancy. With complications involved in the current treatment strategies, alternates including the use of phytochemicals have gained fame. Cranberries are known for their exceptional health benefits and have been explored for their effective activities in various cancers. The current study aimed at evaluating the anti-cancer properties of cranberry juice concentrate (CJC) on MG-63 cell line for human osteosarcoma, by investigating its apoptotic activity through changes in cell viability and mitochondrial membrane potential. Materials and Methods: Cranberry juice concentrate was obtained by pulverization and lyophilization. The MG-63 cells were treated with 12.5-800 mu g/mL of the CJC and incubated for 24, 48, and 72 hr. The percentage cell viability and IC50 values were obtained. The mitochondrial membrane potential and nuclear changes were examined. The induction of apoptosis was studied by flow cytometer using BD cell Quest 7.5.3 software. GraphPad Prism was used for statistical analysis with significant p-value at <0.05. Results: The IC50 values obtained for CJC were 847.9, 637.4, and 440.6 mu g/mL for 24, 48, and 72 hr respectively. Change in the mitochondrial membrane potential and nuclear morphology was observed following incubation with CJC. Flow cytometric analysis shows cells detected at early and late apoptoic stages after treatment with CJC. Conclusion: Our result suggests that CJC has significant effects on MG-63 osteosarcoma cells and can be considered to supplement conventional therapeutic strategies.