PURPOSE: Cranberries are a rich source of polyphenolic antioxidants. Purified sugars or artificial sweeteners are being added to cranberry-based food products to mask tartness. Refined sugar and artificial sweeteners intake modulate gut microbiota and result in metabolic complications. We evaluated effects of isomalto-oligosaccharides (IMOs; sweet tasting non-digestible oligosaccharides) with cranberry extract (CRX) on high fat diet (HFD)-induced metabolic alterations in mice. METHODS: Male Swiss albino mice were fed normal chow or HFD (58% fat kcal), and were administered either CRX (200 mg/kg) alone or in combination with IMOs (1 g/kg). Cecal short-chain fatty acids, abundances of selected (1) butyrate producing, (2) metabolically beneficial, and (3) selective lipopolysaccharides producing gram negative gut bacteria were studied. Further, gut-related histological, biochemical, genomic changes along with circulating pro-/anti-inflammatory markers and systemic obesity-associated metabolic changes were studied. RESULTS: Co-supplementation of CRX and IMOs significantly improved cecal SCFAs, especially butyrate levels, selected butyrate-producing bacteria (clostridial cluster XIVa bacteria) and butyrate kinase expression in HFD-fed mice. The combination also significantly improved gut beneficial bacterial abundance, gut histology and related changes (colon mucin production, gut permeability) as compared to individual agents. It also prevented HFD-induced systemic and tissue inflammation, glucose intolerance and systemic obesity-associated metabolic changes in adipose tissue and liver. The combination of CRX and IMOs appeared more effective in the prevention of HFD-induced gut derangements. CONCLUSION: Combination of CRX and IMOs could be advantageous for normalization of metabolic alterations seen in diet-induced obesity via beneficial modulation of gastrointestinal health.

OBJECTIVES: The aim of this study was to evaluate the effect of Cranberry and Grape seed-enriched extract gels in inhibiting wear and degradation of demineralized organic matrix (DOM). DESIGN: 225 dentin specimens obtained from bovine incisors were randomly allocated into 5 groups (n=45): 10% Grape seed extract gel (GSE), 10% Cranberry extract gel (CE), 0.012% Chlorhexidine gel (CX), 1.23% NaF gel (F), and no active compound gel (P, placebo). Before the treatments, samples were demineralized by immersion in 0.87M citric acid, pH 2.3 (36h). Then, the studied gels were applied once over dentin for 1min. Next, the samples were immersed in artificial saliva containing collagenase obtained from Clostridium histolyticum for 5days. The response variable for dentin wear was depth of dentin loss measured by profilometry and for collagen degradation was hydroxyproline determination. Data were analyzed by ANOVA followed by Tukey's test and Pearson Correlation Test (p<0.05). RESULTS: Grape seed extract significantly reduced dentin wear compared to the other groups (p<0.05). Cranberry extract and Chlorhexidine did not differ statistically and were able to reduce wear when compared to NaF and placebo treatments. The hydroxyproline analysis showed that there was no significant difference among groups for all treatments (p<0.05). Correlation analysis showed a significant correlation between the amount of degraded DOM evaluated by profilometry and the determination of hydroxyproline. CONCLUSION: Cranberry extract was able to reduce the dentin wear and collagen degradation, likely due to the proanthocyanidin content and its action. Therefore, Cranberry could be suggested as an interesting natural-based agent to prevent dentin erosion.

OBJECTIVE: To investigate the hepatoprotective efficacy of cranberry extract (CBE) against carbon tetrachloride (CCl4)-induced hepatic injury using in-vivo animal model. METHODS: The hepatoprotective efficacy of CBE (200 and 400 mg/kg) was investigated against CCl4 (4 mL/kg)-induced hepatotoxicity, elevated liver enzymes [ALT (alanine aminotransferase), AST (aspartate aminotransferase), and alkaline phosphatase (ALP)], and total protein (TP) contents in the serum. Moreover, CBE-aided antioxidant defense against hepatotoxic insult of CCl4 was measured by evaluating a number of anti-oxidative biomarkers including reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) in the serum by using spectrophotometric analyses. RESULTS: Results showed that the exposure of experimental animals to CCl4 did induce significant hepatotoxicity compared to the non-induced (untreated) group. The oral administration of CBE demonstrated a significant dose-dependent alleviation in the liver enzymes (AST, ALT, and ALP), increased antioxidant defense (GSH, SOD, and CAT), and reduced MDA levels in the serum of treated animals compared to the animals without treatment. The resulting data showed that the administration of CBE decreased the serum levels of ALT, AST, and ALP compared to the CCl4-induced group. CONCLUSIONS: The resulting data evidenced that CBE exhibits promising hepatoprotective potential against the chemical induced hepatotoxicity, maintains homeostasis in liver enzymes, and can provide significant antioxidant defense against free radicals-induced oxidative stress.

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 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.

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.

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.

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.

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.

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.