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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.

Cranberry Anthocyanin as an Herbal Medicine Lowers Plasma Cholesterol by Increasing Excretion of Fecal Sterols.

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Authors
Wang L, Zhu H, Zhao Y, Jiao R, Lei L, Chen J, Wang X, Zhang Z, Huang Y, Wang T, Chen ZY.
Journal
Phytomedicine; 38:98-106
Abstract

Background: Interest in using herbal medicines to treat the hypercholesterolemia is increasing. Cranberry extract could decrease plasma cholesterol, however, the active ingredients and the underlying mechanisms remain largely unknown. Hypothesis: The present study was to test the hypothesis that cranberry anthocyanins (CrA) were at least one of the active ingredients responsible for the cholesterol-lowering activity of cranberry fruits via a mechanism of increasing fecal sterol excretion. Methods: Forty-four hamsters were randomly divided into five groups and fed one of the five diets, namely a non-cholesterol control diet (NCD), a high-cholesterol control diet (HCD), a HCD diet supplemented with a low dose of 1% CrA (CL), a HCD diet supplemented with a high dose of 2% CrA (CH), and a HCD diet supplemented with 0.5% cholestyramine as a positive control drug (P-CTL), respectively, for six weeks. Plasma lipoprotein cholesterol was quantified using the enzymatic kits, while the gene expressions of transporters, enzymes and receptors involved in cholesterol absorption and metabolism were quantified using the quantitative RT-PCR. Fecal sterols were quantified using gas chromatography (GC). Results: Plasma total cholesterol and aorta atherosclerotic plaque decreased dose-dependently with the increasing amounts of CrA added into diets. This was accompanied by a dose-dependent increase in excretion of both neutral and acidic sterols. CrA had no effect on the mRNA levels of intestinal Niemann-Pick C1 like 1 protein (NPC1 L1), acyl CoA:cholesterol acyltransferase2 (ACAT2), microsomal triacylglycerol transport protein (MTP), and ATP binding cassette transporter 5 (ABCG5) as well as hepatic cholesterol-7 alpha -hydroxylase (CYP7A1), 3-Hydroxy-3-methylglutaryl reductase (HMG-CoA-R), sterol regulatory element binding protein 2 (SREBP2), LDL receptor (LDL-R), and Liver X receptor alpha (LXR alpha ). Conclusion: CrA as an herbal medicine could favorably modify the lipoprotein profile in hamsters fed a high cholesterol diet by enhancing excretion of fecal neutral and acidic sterols, most likely not mediated by interaction with genes of transporters, enzymes and proteins involved in cholesterol absorption and metabolism

Cranberry Antioxidant Power on Oxidative Stress, Inflammation and Mitochondrial Damage.

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Authors
Caldas, APS; Coelho, OGL; Bressan J.
Journal
International Journal of Food Properties, 21:1, 582-592, DOI: 10.1080/10942912.2017.1409758
Abstract

The American cranberry (Vaccinium macrocarpon) is one of the fruits containing antioxidants in great quantity and of high quality. From recent research, it is evident that both cranberry and its products, when consumed chronically or acutely, boost the antioxidant effect. Likewise, most studies revealed the anti-inflammatory potential of the cranberry polyphenols. Both effects exert direct action mechanisms, revealed by the ability of the polyphenols to remove the reactive oxygen species, as well as indirect effects, represented by the action of these phytochemicals on the cell signaling pathways and genetic expression. A limited number of articles that evaluated the effects of cranberry on mitochondrial damages are available. However, an enhancement in the functions of this organelle was confirmed by the increased production of adenosine triphosphate (ATP). Therefore, further studies are required to demonstrate the benefits credited to the use of cranberry, as well as to describe the action mechanisms of the polyphenols.

Cranberry Proanthocyanidin-Chitosan Hybrid Nanoparticles as a Potential Inhibitor of Extra-Intestinal Pathogenic Escherichia Coli Invasion of Gut Epithelial Cells.

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Authors
Alfaro-Viquez E; Esquivel-Alvarado D; Madrigal-Carballo S; Krueger CG; Reed JD.
Journal
International Journal of Biological Macromolecules. 111:415-420
Abstract

Chitosan interacts with proanthocyanidins through hydrogen-bonding, which allows encapsulation and development of stable nanoparticles via ionotropic gelation. Cranberry proanthocyanidins (PAC) are associated with the prevention of urinary tract infections and PAC inhibit invasion of gut epithelial cells by extra-intestinal pathogenic Escherichia coli (ExPEC). We determined the effect of cranberry proanthocyanidin-chitosan hybrid nanoparticles (PAC-CHTNp) on the ExPEC invasion of gut epithelial cells in vitro. PAC-CHTNp were characterized according to size, morphology, and bioactivity. Results showed a decrease in the size of the nanoparticles as the concentration of PAC was increased, indicating that PAC increases cross-linking by hydrogen-bonding on the surface of the chitosan nanoparticles. Nanoparticles were produced with diameters ranging from 367.3nm to 293.2nm. Additionally, PAC-CHTNp significantly inhibited the ability of ExPEC to invade the enterocytes by ~80% at 66mugGAE/mL and by ~92% at 100mugGAE/mL. Results also indicate that chitosan nanoparticles alone were not significantly different from controls in preventing ExPEC invasion of enterocytes (data not shown) and also there were not significant differences between PAC alone and PAC-CHTNp, suggesting that the new PAC-CHTNp could lead to an increase in the stability of encapsulated PAC, maintain the molecular adhesion of PAC to ExPEC.

Cranberry Supplementation Does Not Reduce Urinary Tract Infections in Patients With Indwelling Catheters After Pelvic Reconstructive Surgery.

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Authors
Shatkin-Margolis A; Warehime J; Pauls RN.
Journal
Female Pelvic Medicine & Reconstructive Surgery. 24(2):130-134
Abstract

OBJECTIVES: Urinary tract infections (UTIs) are common after pelvic reconstructive surgery, likely due to high rates of urinary retention. We sought to determine if prescription of cranberry capsules reduced UTIs in postoperative patients requiring catheter use. METHODS: This was an institutional review board-approved retrospective cohort study. Two 6-month periods were compared: April to September 2015, before cranberry capsules were incorporated, and April to September 2016, after cranberry capsules were implemented. Our study population included patients discharged with a catheter after pelvic reconstructive surgery. All charts were reviewed for demographics, perioperative data, and urine cultures up to 6 weeks postoperatively. A UTI was defined as treatment with antibiotics or positive cultures. Statistical analysis was performed; logistic regression evaluated for relationships between UTI and other factors. Our a priori sample size calculation determined 88 subjects per group would be necessary. RESULTS: Over the 2 periods, 167 patients met inclusion criteria: 71 before and 96 after cranberry implementation. The 2 cohorts were similar in all data. Regarding incidence of UTI, rates were overall high and not significantly different between groups (76% before cranberry vs 69% with cranberry; P = 0.299). The median duration of catheter use was 8 days in both cohorts. The UTI was most likely to occur in the second week after surgery. Logistic regression revealed no associations between age, surgery type, duration of catheter use, and UTI. CONCLUSIONS: In this retrospective study, prescription of cranberry capsules did not significantly reduce UTI rates among patients with urinary catheters after pelvic reconstructive surgery.