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Inhibitory Activity of Chokeberry, Bilberry, Raspberry and Cranberry Polyphenol-Rich Extract Towards Adipogenesis and Oxidative Stress in Differentiated 3T3-L1 Adipose Cells.

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Authors
Kowalska K, Olejnik A, Szwajgier D, Olkowicz M.
Journal
PLoS ONE 12(11):e0188583
Abstract

Berries are a rich source of antioxidants and phytochemicals that have received considerable interest for their possible relations to human health. In this study, the anti-adipogenic effect of polyphenol-rich extract obtained from chokeberry Aronia melanocarpa (Michx.) Elliot, raspberry Rubus idaeus L., bilberry Vaccinium myrtillus L. and cranberry Vaccinium macrocarpon Aiton fruits and its underlying molecular mechanisms were investigated in differentiated 3T3-L1 adipose cells. Treatment with the extract (25-100 mug/mL) significantly decreased lipid accumulation and reactive oxygen species generation in adipocytes without showing cytotoxicity. Real-time PCR analysis revealed that the extract at a concentration of 100 mug/mL suppressed adipogenesis and lipogenesis via the down-regulation of PPARgamma (67%), C/EBPalpha (72%), SREBP1 (62%), aP2 (24%), FAS (32%), LPL (40%), HSL (39%), and PLIN1 (32%) gene expression. Moreover, the extract significantly increased the expression of adiponectin (4.4-fold) and decreased leptin expression (90%) and respectively regulated the production of these adipokines in 3T3-L1 adipocytes. The obtained results suggest that the analyzed extract may be a promising source of bioactive compounds that support long-term weight maintenance and promote the effective management of obesity.

The Ameliorative Role of Cranberry Extract and Bone Marrow Cells Against Chlorambucil Cytotoxicity in Rat Fertility

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Authors
Nafie, E. H. O. Khater, E. Awwad, M. Zowail, M. Hegazy, K.
Journal
African Journal of Biotechnology; 2017. 16(6):274-279
Abstract

The objective of the current study was to evaluate and compare the effectiveness of cranberry extracts and bone marrow cells against chlorambucil (CHB) effect on rats' fertility. Forty adult male albino rats were divided randomly into eight equal groups as the following; normal control, rats injected orally with 0.2 mg/kg of CHB for 14 days, rats injected orally with 100 mg/kg of cranberry extract (CB) for ten days, rats intravenously injected with bone marrow cells (BMC) through tail vain, rats protected with both CB and BMC, rats treated with CHB+CB, rats treated with CHB+BMC and rats treated with CHB+BMC+CB. Genotoxicity were evaluated by counting and comparing the value of sperm abnormalities and normal sperm count. Results show that rats injected with CHB had remarkable increase in sperm head abnormalities as without hook, banana shape and hummer shape. Admission of cranberry extract and bone marrow cells after chemotherapy improved the frequency of the sperm abnormalities.

The Antiadhesive Activity of Cranberry Phytocomplex Studied by Metabolomics: Intestinal PAC-A Metabolites But not Intact PAC-A are Identified as Markers in Active Urines Against Uropathogenic Escherichia Coli.

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Authors
Peron G; Sut S; Pellizzaro A; Brun P; Voinovich D; Castagliuolo I; Dall'Acqua S.
Journal
Fitoterapia. 122:67-75
Abstract

Cranberry procyanidins and quercetin derivatives are considered possible active compounds against urinary tract infections (UTIs). In this paper a small group (n=6) of healthy subjects consumed a product containing 360mg of cranberry extract (42.6% w/w of PAC-A and 14.6% w/w of PAC-B) and 200mg of quercetin. Urine samples were collected after 2,4,6,8, and 24h. The changes in antiadhesive properties against urophatogenic E. coli of the urinary output were determined in vitro and modification to urinary metabolome were studied by LC-MS. Significant antiadhesive properties of urine samples were observed, with the greatest effect 6-8h after oral administration, confirming the possible usefulness of cranberry containing products in urinary tract infections (UTI). Metabolomic analysis revealed that valeric acid and valerolactone derivatives that were detected in 6 and 8h sample, while 4-hydroxy-5-(phenyl)-valeric acid-O-glucuronide and 5-(3',4'-dihydroxyphenyl)-gamma-valerolactone at 6h and 4-hydroxy-5-(phenyl)-valeric acid-O-sulphate, 3-hydroxyphenyl-valeric acid, 5-(4'-hydroxyphenyl)-gamma-valerolactone-4'-O-glucuronide and 4-hydroxy-5-(3'-hydroxyphenyl)-valeric acid-3'-O-sulphate were the most abundant at 8h. The present study shows that the antiadhesive properties of urine sample after cranberry consumption are not ascribable to the direct effect of PAC-A, because their levels in urinary output are in the range of ng/mL. On the other hand, significant metabolites that were detected are mainly metabolites of intestinal action on polyphenols and PACs, as well as glucuronidated and sulphated quercetin, suggesting an important role of intestinal modification of phytoconstituents in the cranberry extract mechanism of action.

The Effect of Cranberry Juice Consumption on the Recurrence of Urinary Tract Infection: Relationship to Baseline Risk Factors

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Authors
Maki KC; Nieman KM; Schild AL; Kaspar KL; Khoo C.
Journal
Am J Clin Nutr. https://doi.org/10.1080/07315724.2017.1370398
Abstract

OBJECTIVE: The objective of this study was to assess relationships between clinical predictors of urinary tract infection (UTI) and effects of cranberry juice consumption on recurrence in a post hoc analysis of a 24-week, randomized, double-blind, placebo-controlled, multicenter clinical trial in women with a recent history of UTI. METHODS: Participants consumed a cranberry (n = 185) or placebo (n = 188) beverage (240 mL) daily. Odds ratios (OR) from 20 candidate predictor variables were evaluated in univariate analyses to assess clinical UTI incidence relationships in the placebo group. A multivariate logistic regression model was developed. The effects of cranberry juice consumption were evaluated in subsets categorized by the likelihood of a UTI event based on the prediction model. RESULTS: In the placebo group, the final multivariate regression model identified four variables associated with the odds for having >= 1 UTI: intercourse frequency >= 1 time during the prior 4 weeks (OR: 2.36; 95% confidence interval [CI]: 0.98, 5.71; p = 0.057), use of vasectomy or hormonal methods for contraception (OR: 2.58; 95% CI: 1.20, 5.58; p = 0.016), most recent UTI 90 days prior to screening (OR: 2.28; 95% CI; 1.12, 4.67; p = 0.024), and living in France compared with the United States (OR: 0.17; 95% CI: 0.04, 0.79; p = 0.024). Three propensity categories were investigated (24-week probability 10%, 10%-21%, and > 21%). Incidence rate ratios for the cranberry vs placebo groups were 0.76 (95% CI: 0.22, 2.60; p = 0.663) for those with 10% probability, 0.73 (95% CI: 0.35, 1.53; p = 0.064) for those with 10% to 21% probability, and 0.58 (95% CI: 0.35, 0.97; p = 0.039) for those with > 21% probability. CONCLUSIONS: Results suggest that clinical predictors identify women with low and high risk of clinical UTI recurrence, which may be useful for design of clinical studies evaluating preventive therapies.

The Impact of Cranberry (Vaccinium macrocarpon) and Cranberry Products on Each Component of the Metabolic Syndrome: a Review

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Authors
Thimóteo NSB, Scavuzzi BM, Simão ANC, Dichi I.
Journal
Nutrire 42:25, https://doi.org/10.1186/s41110-017-0048-8
Abstract

Background: Some studies have shown that cranberry (Vaccinium macrocarpon) has beneficial effects on the components of the metabolic syndrome (MetS), a condition characterized by a cluster of cardiovascular risk factors such as central obesity, hypertension, impaired glucose homeostasis, elevated triglycerides, and decreased HDL cholesterol levels. Cranberry is very rich in polyphenols, which may significantly reduce cardiovascular disease (CVD) risk. Main body of the abstract: Nutritional intervention studies have indicated that the intake of cranberries and cranberry products may have the following impact on metabolic health: (1) attenuate markers of obesity such as body weight, body mass index, and waist circumference; (2) reduce systolic and diastolic pressures; (3) decrease plasma concentrations of triglycerides and oxidized LDL-cholesterol, as well as increase HDL cholesterol; and (4) promote glucose homeostasis. In addition, nutritional intervention with cranberries could confer antioxidant and anti-inflammatory properties and the ability to reduce biomarkers of atherosclerosis associated with the MetS, such as homocysteine. Short conclusion: Although there has been promising results, particularly related to lipid profile and blood pressure, further research is needed to support the recommendation of cranberry intake as a nutritional intervention for the treatment of MetS.

The Role of Cranberry in Preventing Urinary Tract Infection in Children; a Systematic Review and Meta-Analysis.

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Authors
Roshdibonab F, Mohammadbager FazlJoo S, Torbati M, Mohammadi G, Asadloo M, Noshad H
Journal
International Journal of Pediatrics, 5 (12). pp. 6457-6468.
Abstract

Introduction: Although effectiveness of cranberry for preventing urinary tract infection (UTI) has been reported in Iranian traditional medicine and recent studies there is still controversy in this regard. Therefore, the present study was designed with a meta-analytic approach aiming to evaluate the effect of prophylaxis prescription of cranberry in prevention of UTI in children.Methods: In this study, a thorough search was performed in Medline, Embase, Web of Sciences, Scopus and CINHAL databases by the end of August 2017. Using keywords related to urinary tract infection combined with words related to cranberry, search strategy was designed. The articles were summarized and finally, the role of cranberry extract consumption in decreasing the incidence of UTI was evaluated by reporting odds ratio (OR) and 95 confidence interval (95 CI). Results: In the end, 10 studies were included (414 cases in control group and 380 in cranberry extract treatment group). Analyses showed that prescription of cranberry significantly reduced the odds of UTI manifestation in children compared to placebo (OR=0.31; 95 CI: 0.21 to 0.46; p

5-(3',4'-dihydroxyphenyl)- Gamma -Valerolactone and its Sulphate Conjugates, Representative Circulating Metabolites of Flavan-3-ols, Exhibit Anti-Adhesive Activity Against Uropathogenic Escherichia Coli in Bladder Epithelial Cells.

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Authors
Mena, P. Llano, D. G. de Brindani, N. Esteban-Fernandez, A. Curti, C. Moreno-Arribas, M. V. Rio, D. del Bartolome, B.
Journal
Journal of Functional Foods 29:275-280
Abstract

Urinary tract infections (UTI) are mostly caused by uropathogenic Escherichia coli (UPEC). Cranberry-based products have shown preventive effects against UTI, and this has been partially attributed to their A-type proanthocyanidin content. However, recent evidence reports phenyl- gamma -valerolactones as the most relevant urinary metabolites of cranberry procyanidins, and candidates these compounds as plausible responsible for the protective effects of cranberries against UTI. This paper studied the inhibition of the adherence of UPEC ATCCReg. 53503TM to T24 bladder epithelial cells by physiological concentrations of differently sulphated dihydroxyphenyl- gamma -valerolactones. Moreover, the transformations of these molecules in the cell media were evaluated by UHPLC-MSn. All dihydroxyphenyl- gamma -valerolactone derivatives showed anti-adhesive activity at 100 micro M, while 5-(3'-hydroxyphenyl)- gamma -valerolactone-4-O-sulphate also showed neuro-protective effects at 50 micro M. Some compounds underwent extensive metabolism during cell incubation, mainly deconjugation of sulphate moieties and opening of the lactone ring. These results shed light on the flavan-3-ol metabolites behind the prophylactic effect of cranberries against UTI.

A Human Gut Commensal Ferments Cranberry Carbohydrates to Produce Formate.

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Authors
Ozcan E; Sun J; Rowley DC; Sela DA.
Journal
Applied & Environmental Microbiology 10.1128/AEM.01097-17 [doi]
Abstract

Commensal bifidobacteria colonize the human gastrointestinal tract and catabolize glycans that are impervious to host digestion. Accordingly, Bifidobacterium longum typically secrete acetate and lactate as fermentative endproducts. This study tested the hypothesis that B. longum utilize cranberry-derived xyloglucans in a strain-dependent manner. Interestingly, the B. longum strain that efficiently utilizes cranberry xyloglucans secrete 2.0-2.5 moles acetate:lactate. The 1.5 ratio theoretical yield obtained in hexose fermentations shifts during xyloglucan metabolism. Accordingly, this metabolic shift is characterized by increased acetate and formate production at the expense of lactate. alpha-L-arabinofuranosidase, an arabinan endo-1,5-alpha-L-arabinosidase, and a beta-xylosidase with a carbohydrate substrate-binding protein and carbohydrate ABC transporter membrane proteins are upregulated (> 2-fold change), which suggests carbon flux through this catabolic pathway. Finally, syntrophic interactions occurred with strains that utilize carbohydrate products derived from initial degradation from a heterologous bacterium.IMPORTANCE This is a study of bacterial metabolism of complex cranberry carbohydrates termed xyloglucans that are likely not digested prior to reaching the colon. This is significant as bifidobacteria interact with this dietary compound to potentially impact human host health through energy and metabolite production by bacterial utilization of these substrates. Specific bacterial strains utilize cranberry xyloglucans as a nutritive source indicating unknown mechanisms that are not universal in bifidobacteria. In addition, xyloglucan metabolism proceeds using an alternative pathway could lead to further research to investigate mechanisms underlying this interaction. Finally, we observed cross-feeding between bacteria in which one strain degrades the cranberry xyloglucan to make it available to a second strain. Similar nutritive strategies are known to occur within the gut. In aggregate, this study may lead to novel foods or supplements to impact human health through rational manipulations of their microbiome.

Absorption, Metabolism and Excretion of Cranberry (Poly)Phenols in Humans: a Dose Response Study and Assessment of Inter-Individual Variability

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Authors
Feliciano, R. P. Mills, C. E. Istas, G. Heiss, C. Rodriguez-Mateos, A.
Journal
Nutrients 9(3):268
Abstract

The beneficial health effects of cranberries have been attributed to their (poly)phenol content. Recent studies have investigated the absorption, metabolism and excretion of cranberry (poly)phenols; however, little is known about whether they follow a dose response in vivo at different levels of intake. An acute double-blind randomized controlled trial in 10 healthy men with cranberry juices containing 409, 787, 1238, 1534 and 1910 mg total (poly)phenols was performed. Blood and urine were analyzed by UPLC-Q-TOF-MS. Sixty metabolites were identified in plasma and urine including cinnamic acids, dihydrocinnamic, flavonols, benzoic acids, phenylacetic acids, benzaldehydes, valerolactones, hippuric acids, catechols, and pyrogallols. Total plasma, but not excreted urinary (poly)phenol metabolites, exhibited a linear dose response (r2=0.74, p<0.05), driven by caffeic acid 4-O- beta -D-glucuronide, quercetin-3-O- beta -D-glucuronide, ferulic acid 4-O- beta -D-glucuronide, 2,5-dihydroxybenzoic acid, 2,4-dihydroxybenzoic acid, ferulic acid, caffeic acid 3-O- beta -D-glucuronide, sinapic acid, ferulic acid 4-O-sulfate, 3-hydroxybenzoic acid, syringic acid, vanillic acid-4-O-sulfate, (4R)-5-(3'-hydroxyphenyl)- gamma -valerolactone-4'-O-sulfate, 4-methylgallic acid-3-O-sulfate, and isoferulic acid 3-O-sulfate (all r2 >=0.89, p<0.05). Inter-individual variability of the plasma metabolite concentration was broad and dependent on the metabolite. Herein, we show that specific plasma (poly)phenol metabolites are linearly related to the amount of (poly)phenols consumed in cranberry juice. The large inter-individual variation in metabolite profile may be due to variations in the gut microbiome.

Anti-Aging and Redox State Regulation Effects of A-type Proanthocyanidins-Rich Cranberry Concentrate and its Comparison with Grape Seed Extract in Mice.

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Authors
Jiao JJ, Wei Y, Chen J, Chen X, Zhang Y.
Journal
Journal of Functional Foods 30:63-73
Abstract

We investigated the anti-aging and redox state regulation effects by A-type proanthocyanidins (PACs)-rich cranberry concentrate (CBC) and its comparison with B-type PACs-rich grape seed extract (GSE). Using the Q-Extractive mass spectrometry, PACs dimer A and B were identified as predominant phenolic compounds of CBC and GSE, respectively, while epicatechin was present in both extracts. Using the d-galactose-induced aging mice model, effects were investigated via an 8-week oral gavage considering water-soluble vitamin E as the positive control. Both CBC and GSE reduced hepatic and brain thiobarbituric acid reactive substances, and plasma 8-isoprostane levels by 30-57%, 24-30% and 11-62%, respectively, and decreased brain and plasma monoamine oxidase activities by 27-59% and 65-71%, respectively. CBC could improve hepatic glutathione peroxidase activity by 42%, while GSE increased hepatic superoxide dismutase activity by 13%. Therefore, both extracts exerted anti-aging effects probably via regulating in vivo redox state. However, neither generated any effect on catalase activities.