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Berry (poly)phenols and Cardiovascular Health

Posted
Authors
Rodriguez-Mateos A, Heiss C, Borges G, Crozier A
Journal
J Agric Food Chem 62(18):3842-51
Abstract

Berries are a rich source of (poly)phenols, including anthocyanins, flavan-3-ols, procyanidins, flavonols, ellagitannins, and hydroxycinnamates. Epidemiological evidence indicates that the cardiovascular health benefits of diets rich in berries are related to their (poly)phenol content. These findings are supported by small-scale randomized controlled studies (RCTs) that have shown improvements in several surrogate markers of cardiovascular risk such as blood pressure, endothelial function, arterial stiffness, and blood lipids after acute and short-term consumption of blueberries, strawberries, cranberries, or purified anthocyanin extracts in healthy or diseased individuals. However, firm conclusions regarding the preventive value of berry (poly)phenols cannot be drawn due to the small number of existing studies and limitations that apply to the available data, such as lack of controls or failure to assess the absorption and metabolism of (poly)phenols. Although the current evidence is promising, more long-term RCTs are needed to establish the role of berry (poly)phenols to support cardiovascular health.

Bioactive Compounds and Antioxidant Activity in Different Types of Berries.

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Authors
Skrovankova S, Sumczynski D, Mlcek J, Jurikova T, Sochor J
Journal
Int J Mol Sci 16(10):24673-706
Abstract

Berries, especially members of several families, such as Rosaceae (strawberry, raspberry, blackberry), and Ericaceae (blueberry, cranberry), belong to the best dietary sources of bioactive compounds (BAC). They have delicious taste and flavor, have economic importance, and because of the antioxidant properties of BAC, they are of great interest also for nutritionists and food technologists due to the opportunity to use BAC as functional foods ingredients. The bioactive compounds in berries contain mainly phenolic compounds (phenolic acids, flavonoids, such as anthocyanins and flavonols, and tannins) and ascorbic acid. These compounds, either individually or combined, are responsible for various health benefits of berries, such as prevention of inflammation disorders, cardiovascular diseases, or protective effects to lower the risk of various cancers. In this review bioactive compounds of commonly consumed berries are described, as well as the factors influencing their antioxidant capacity and their health benefits.

Comparison of the anti-adhesion activity of three different cranberry extracts on uropathogenic P-fimbriated Escherichia coli: a randomized, double-blind, placebo controlled, ex vivo, acute study

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Authors
Howell A, Souza D, Roller M, Fromentin E
Journal
Nat Prod Commun 10(7):1215-8
Abstract

Research suggests that cranberry (Vaccinium macrocarpon) helps maintain urinary tract health. Bacterial adhesion to the uroepithelium is the initial step in the progression to development of a urinary tract infection. The bacterial anti-adhesion activity of cranberry proanthocyanidins (PACs) has been demonstrated in vitro. Three different cranberry extracts were developed containing a standardized level of 36 mg of PACs. This randomized, double-blind, placebo controlled, ex vivo, acute study was designed to compare the anti-adhesion activity exhibited by human urine following consumption of three different cranberry extracts on uropathogenic P-fimbriated Escherichia coli in healthy men and women. All three cranberry extracts significantly increased anti-adhesion activity in urine. from 6 to 12 hours after intake of a single dose standardized to deliver 36 mg of PACs (as measured by the BL-DMAC method), versus placebo.

Cranberry (Vaccinium macrocarpon) Oligosaccharides Decrease Biofilm Formation by Uropathogenic Escherichia Coli.

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Authors
Sun J, Marais JP, Khoo C, LaPlante K, Vejborg RM, Givskov M, Tolker-Nielsen T, Seeram NP, Rowley DC
Journal
J Funct Food 17:235-242
Abstract

The preventive effects of the American cranberry (Vaccinium macrocarpon) against urinary tract infections are supported by extensive studies which have primarily focused on its phenolic constituents. Herein, a phenolic-free carbohydrate fraction (designated cranf1b-F2) was purified from cranberry fruit using ion exchange and size exclusion chromatography. MALDI-TOF-MS analysis revealed that the cranf1b-F2 constituents are predominantly oligosaccharides possessing various degrees of polymerisation and further structural analysis (by GC-MS and NMR) revealed mainly xyloglucan and arabinan residues. In antimicrobial assays, cranf1b-F2 (at 1.25 mg/mL concentration) reduced biofilm production by the uropathogenic Escherichia coli CFT073 strain by over 50% but did not inhibit bacterial growth. Cranf1b-F2 (ranging from 0.625 to 10 mg/mL) also inhibited biofilm formation of the non-pathogenic E. coli MG1655 strain up to 60% in a concentration-dependent manner. These results suggest that cranberry oligosaccharides, in addition to its phenolic constituents, may play a role in its preventive effects against urinary tract infections.

Cranberry Anthocyanin Extract Prolongs Lifespan of Fruit Flies

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Authors
Wang L, Li YM, Lei L, Liu Y, Wang X, Ma KY, Chen ZY
Journal
Exp Gerontol 69:189-95
Abstract

Cranberry is an excellent source of dietary antioxidants. The present study investigated the effect of cranberry anthocyanin (CrA) extract on the lifespan of fruit flies with focus on its interaction with aging-related genes including superoxide dismutase (SOD), catalase (CAT), methuselah (MTH), insulin receptor (InR), target of rapamycin (TOR), hemipterus (Hep), and phosphoenolpyruvate carboxykinase (PEPCK). Results showed that diet containing 20mg/mL CrA could significantly prolong the mean lifespan of fruit flies by 10% compared with the control diet. This was accompanied by up-regulation of SOD1 and down-regulation of MTH, InR, TOR and PEPCK. The stress resistance test demonstrated that CrA could reduce the mortality rate induced by H2O2 but not by paraquat. It was therefore concluded that the lifespan-prolonging activity of CrA was most likely mediated by modulating the genes of SOD1, MTH, InR, TOR and PEPCK.

Cranberry Extract-Enriched Diets Increase NAD(P)H:quinone Oxidoreductase and Catalase Activities in Obese but not in Nonobese Mice

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Authors
Bousova I, Bartikova H, Matouskova P, Lnenickova K, Zappe L, Valentova K, Szotakova B, Martin J, Skalova L
Journal
Nutr Res 35(10):901-9
Abstract

Consumption of antioxidant-enriched diets is 1 method of addressing obesity, which is associated with chronic oxidative stress and changes in the activity/expression of various enzymes. In this study, we hypothesized that the modulation of antioxidant enzymes and redox status through a cranberry extract (CBE)-enriched diet would differ between obese and nonobese mice. The CBE used in this study was obtained from the American cranberry (Vaccinium macrocarpon, Ericaceae), a popular constituent of dietary supplements that is a particularly rich source of (poly)phenols and has strong antioxidant properties. The present study was designed to test and compare the in vivo effects of 28-day consumption of a CBE-enriched diet (2%) on the antioxidant status of nonobese mice and mice with monosodium glutamate-induced obesity. Plasma, erythrocytes, liver, and small intestine were studied concurrently to obtain more complex information. The specific activities, protein, and messenger RNA expression levels of antioxidant enzymes as well as the levels of malondialdehyde and thiol (SH) groups were analyzed. Cranberry extract treatment increased the SH group content in plasma and the glutathione S-transferase activity in the erythrocytes of the obese and nonobese mice. In addition, in the obese animals, the CBE treatment reduced the malondialdehyde content in erythrocytes and increased
NAD(P)H: quinone oxidoreductase (liver) and catalase (erythrocytes and small intestine) activities. The elevation of hepatic
NAD(P)H: quinone oxidoreductase activity was accompanied by an increase in the corresponding messenger RNA levels. The effects of CBE on the activity of antioxidant enzymes and redox status were more pronounced in the obese mice compared with the nonobese mice.

Cranberry Flavonoids Modulate Cariogenic Properties of Mixed-Species Biofilm through Exopolysaccharides-Matrix Disruption

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Authors
Kim D, Hwang G, Liu Y, Wang Y, Singh AP, Vorsa N, Koo H
Journal
PLoS ONE 10(12):e0145844
Abstract

The exopolysaccharides (EPS) produced by Streptococcus mutans-derived glucosyltransferases (Gtfs) are essential virulence factors associated with the initiation of cariogenic biofilms. EPS forms the core of the biofilm matrix-scaffold, providing mechanical stability while facilitating the creation of localized acidic microenvironments. Cranberry flavonoids, such as A-type proanthocyanidins (PACs) and myricetin, have been shown to inhibit the activity of Gtfs and EPS-mediated bacterial adhesion without killing the organisms. Here, we investigated whether a combination of cranberry flavonoids disrupts EPS accumulation and S. mutans survival using a mixed-species biofilm model under cariogenic conditions. We also assessed the impact of cranberry flavonoids on mechanical stability and the in situ pH at the biofilm-apatite interface. Topical application of an optimized combination of PACs oligomers (100-300 muM) with myricetin (2 mM) twice daily was used to simulate treatment regimen experienced clinically. Treatments with cranberry flavonoids effectively reduced the insoluble EPS content (>80% reduction vs. vehicle-control; p0.001), while hindering S. mutans outgrowth within mixed-species biofilms. As a result, the 3D architecture of cranberry-treated biofilms was severely compromised, showing a defective EPS-matrix and failure to develop microcolonies on the saliva-coated hydroxyapatite (sHA) surface. Furthermore, topical applications of cranberry flavonoids significantly weaken the mechanical stability of the biofilms; nearly 90% of the biofilm was removed from sHA surface after exposure to a shear stress of 0.449 N/m2 (vs. 36% removal in vehicle-treated biofilms). Importantly, in situ pH measurements in cranberry-treated biofilms showed significantly higher pH values (5.2 +/- 0.1) at the biofilm-apatite interface vs. vehicle-treated biofilms (4.6 +/- 0.1). Altogether, the data provide important insights on how cranberry flavonoids treatments modulate virulence properties by disrupting the biochemical and ecological changes associated with cariogenic biofilm development, which could lead to new alternative or adjunctive antibiofilm/anticaries chemotherapeutic formulations.

Cranberry Proanthocyanidins Inhibit Esophageal Adenocarcinoma In Vitro and In Vivo Through Pleiotropic Cell Death Induction and PI3K/AKT/mTOR Inactivation.

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Authors
Kresty LA, Weh KM, Zeyzus-Johns B, Perez LN, Howell AB
Journal
Oncotarget 6(32):33438-55
Abstract

Cranberries are rich in bioactive constituents known to improve urinary tract health and more recent evidence supports cranberries possess cancer inhibitory properties. However, mechanisms of cancer inhibition by cranberries remain to be elucidated, particularly in vivo. Properties of a purified cranberry-derived proanthocyanidin extract (C-PAC) were investigated utilizing acid-sensitive and acid-resistant human esophageal adenocarcinoma (EAC) cell lines and esophageal tumor xenografts in athymic NU/NU mice. C-PAC induced caspase-independent cell death mainly via autophagy and low levels of apoptosis in acid-sensitive JHAD1 and OE33 cells, but resulted in cellular necrosis in acid-resistant OE19 cells. Similarly, C-PAC induced necrosis in JHAD1 cells pushed to acid-resistance via repeated exposures to an acidified bile cocktail. C-PAC associated cell death involved PI3K/AKT/mTOR inactivation, pro-apoptotic protein induction (BAX, BAK1, deamidated BCL-xL, Cytochrome C, PARP), modulation of MAPKs (P-P38/P-JNK) and G2-M cell cycle arrest in vitro. Importantly, oral delivery of C-PAC significantly inhibited OE19 tumor xenograft growth via modulation of AKT/mTOR/MAPK signaling and induction of the autophagic form of LC3B supporting in vivo efficacy against EAC for the first time. C-PAC is a potent inducer of EAC cell death and is efficacious in vivo at non-toxic behaviorally achievable concentrations, holding promise for preventive or therapeutic interventions in cohorts at increased risk for EAC, a rapidly rising and extremely deadly malignancy.

Cranberry Products for the Prophylaxis of Urinary Tract Infections in Pediatric Patients.

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Authors
Durham SH, Stamm PL, Eiland LS
Journal
Ann Pharmacother 49(12):1349-56
Abstract

OBJECTIVE: To evaluate the existing data regarding the use of cranberry products for the prevention of urinary tract infections (UTIs) in pediatric patients.
DATA SOURCES: A literature search of Medline databases from 1966 to June 2015 was conducted.
STUDY SELECTION AND DATA EXTRACTION: The databases were searched using the terms ""pediatrics,"" ""children,"" ""cranberry,"" ""cranberry juice,"" and ""urinary tract infections."" The identified trials were then searched for additional references applicable to this topic.
DATA SYNTHESIS: A total of 8 clinical trials were identified that examined the use of cranberry products, mostly juice, for the prevention of UTIs in children. Three trials examined the use in otherwise healthy children. Five trials examined the use in pediatric patients with underlying urogenital abnormalities of which 2 compared cranberry to antibiotics. In healthy pediatric patients, cranberry use was associated with a reduction in the overall number of UTIs and a decrease in the number of antibiotic days per year for UTI treatment. In patients with urogenital abnormalities, results were conflicting, with some studies showing no reduction in UTIs compared with placebo, but others demonstrating a significant reduction. However, cranberry products had similar efficacy when compared with both cefaclor and trimethoprim. All studies used a wide variety of doses and frequencies of cranberry, making specific product recommendations difficult.
CONCLUSIONS: Cranberry appears effective for the prevention of UTIs in otherwise healthy children and is at least as effective as antibiotics in children with underlying urogenital abnormalities. However, recommendations for cranberry dosing and frequency cannot be confidently made at this time. Larger, well-designed trials are recommended.

Effect of Dried Powder Preparation Process on Polyphenolic Content and Antioxidant Capacity of Cranberry (Vaccinium macrocarpon L.).

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Authors
Oszmianski J, Kolniak-Ostek J, Lachowicz S, Gorzelany J, Matlok N
Journal
Ind Crop Prod 77:658-665.
Abstract

The aim of the study was to evaluate the effect of the degree of fragmentation of cranberry fruit (Vaccinium macrocarpon L.) on the chemical composition and antioxidant activity of fruit powders and lyophilized pomace and juices. In analyzed samples, the basic chemical composition, total polyphenolics and antioxidant capacity were determined. Thirty-nine polyphenolic compounds, including 9 phenolic acids, 7 anthocyanins, 9 flavan-3-ols and 14 flavonols, were identified. Polyphenolic concentrations in pomaces ranged from 16 038.74 mg/100 g DW in samples from whole fruits to 17 802.52 mg/100 g DW in samples from crushed fruits. In juices, phenolic concentrations ranged from 873.12 mg/100 g DW in products from whole fruits to 3177.87 mg/100 g DW in products from crushed fruits. Antioxidant capacities were higher in dry products than in juices. The highest DPPH, ABTS and FRAP values were determined in dry pomaces obtained from crushed fruits (156.94, 275.22 and 71.47 micro mol/g DW, respectively).