OBJECTIVE: Previous studies have reported that polyphenol-rich extracts from various sources can prevent obesity and associated gastro-hepatic and metabolic disorders in diet-induced obese (DIO) mice. However, whether such extracts can reverse obesity-linked metabolic alterations remains unknown. In the present study, we aimed to investigate the potential of a polyphenol-rich extract from cranberry (CE) to reverse obesity and associated metabolic disorders in DIO-mice. METHODS: Mice were pre-fed either a Chow or a High Fat-High Sucrose (HFHS) diet for 13 weeks to induce obesity and then treated either with CE (200mg/kg, Chow+CE, HFHS+CE) or vehicle (Chow, HFHS) for 8 additional weeks. RESULTS: CE did not reverse weight gain or fat mass accretion in Chow- or HFHS-fed mice. However, HFHS+CE fully reversed hepatic steatosis and this was linked to upregulation of genes involved in lipid catabolism (e.g., PPARalpha) and downregulation of several pro-inflammatory genes (eg, COX2, TNFalpha) in the liver. These findings were associated with improved glucose tolerance and normalization of insulin sensitivity in HFHS+CE mice. The gut microbiota of HFHS+CE mice was characterized by lower Firmicutes to Bacteroidetes ratio and a drastic expansion of Akkermansia muciniphila and, to a lesser extent, of Barnesiella spp, as compared to HFHS controls. CONCLUSIONS: Taken together, our findings demonstrate that CE, without impacting body weight or adiposity, can fully reverse HFHS diet-induced insulin resistance and hepatic steatosis while triggering A. muciniphila blooming in the gut microbiota, thus underscoring the gut-liver axis as a primary target of cranberry polyphenols.

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.

Urinary tract infections are common infectious diseases which can occur in any part of the urinary tract such as bladder, kidney, ureters, and urethra. They are commonly caused by bacteria that enter through the urethra. Urinary tract infections commonly develop in the bladder and spread to renal tissues. Up to now, there are different antimicrobial agents which have beneficial role on urinary tract infections. However, most of them cause different adverse effects and therefore, much attention has been paid to the search for effective therapeutic agents with negligible adverse effects. Cranberry is known as one of the most important edible plants, which possesses potent antimicrobial effects against the bacteria responsible for urinary tract infections. Growing evidence has shown that cranberry suppresses urinary tract infections and eradicates the bacteria. Therefore, the aim of this study is to critically review the available literature regarding the antimicrobial activities of cranberry against urinary tract infection microorganisms. In addition, we discuss etiology, epidemiology, risk factors, and current drugs of urinary tract infections to provide a more complete picture of this disease.

Background: Cranberry (Vaccinium spp.) has been advocated for treatment of urinary tract infection (UTI); however, its efficacy is controversial. Women have a 50% risk of UTI over their lifetime, and ~20-30% experience a subsequent UTI recurrence.Objective: We conducted this meta-analysis to assess the effect of cranberry on the risk of UTI recurrence in otherwise healthy women.Methods: Literature published before January 2011 was obtained from 2 published systematic reviews, and we conducted updated searches in EMBASE and MEDLINE (through July 2017). We included randomized controlled trials that were conducted in generally healthy nonpregnant women aged >=18 y with a history of UTI, compared cranberry intervention to a placebo or control, and reported the outcome as the number of participants experiencing a UTI. Two researchers conducted abstract and full-text screenings, data extractions, and risk of bias assessments independently, and discrepancies were resolved by group consensus. Meta-analyses were performed by using Stata SE software (version 13). We employed a fixed-effect model using the Mantel-Haenszel method to estimate the summary risk if the heterogeneity was low to moderate (I2 50%). Otherwise, we applied a random-effects model using the DerSimonian-Laird method.Results: We identified 7 randomized controlled trials conducted in healthy women at risk of UTI (n = 1498 participants). Results of the meta-analysis showed that cranberry reduced the risk of UTI by 26% (pooled risk ratio: 0.74; 95% CI: 0.55, 0.98; I2 = 54%). Risk of bias indicated that 2 studies had high loss to follow-up or selective outcome reporting. Overall, the studies were relatively small, with only 2 having >300 participants.Conclusion: These results suggest that cranberry may be effective in preventing UTI recurrence in generally healthy women; however, larger high-quality studies are needed to confirm these findings.

It is increasingly perceived that dietary components have been linked with the prevention of intestinal cancer. Cranberry is a rich source of phenolic constituents and non-digestible fermentable dietary fiber, which shows anti-proliferation effect in colorectal cancer cells. Herein, we investigated the efficacy of long-term cranberry diet on intestinal adenoma formation in Apcmin/+ mice. Apcmin/+ mice were fed a basal diet or a diet containing 20% (w/w) freeze-dried whole cranberry powder for 12 weeks, and the number and size of tumors were recorded after sacrifice. Our results showed that cranberry strongly prevented the growth of intestinal tumors by 33.1%. Decreased cell proliferation and increased apoptosis were observed in tumors of cranberry-fed mice. Cranberry diet reduced the expression profile of colonic inflammatory cytokines (IFN-gamma, IL-1beta and TNF-alpha) accompanied with increased levels of anti-inflammatory cytokines (IL-4 and IL-10). Moreover, the number of colonic goblet cells and MUC2 production were increased, and the intestinal barrier function was also improved. In addition, cranberry diet increased caecal short chain fatty acids concentrations, and down-regulated epidermal growth factor receptor signaling pathway. These data firstly show the efficacy and associated mechanisms of cranberry diet on intestinal tumor growth in Apcmin/+ mice, suggesting its chemopreventive potential against intestinal cancer.

INTRODUCTION: Catheter-associated urinary tract infections (CA-UTIs) are a prevalent and costly condition, with very few therapeutic options. We sought to evaluate the efficacy of an oral cranberry supplement on CA-UTIs over a six-month period. METHODS: Subjects with long-term indwelling catheters and recurrent symptomatic CA-UTIs were enrolled to take a once-daily oral cranberry supplement with 36 mg of the active ingredient proanthocyanidin (PACs). Primary outcome was reducing the number of symptomatic CA-UTIs. This was defined by >=103 (cfu)/mL of >=1 bacterial species in a single catheter urine specimen and signs and symptoms compatible with CA-UTI. Secondary outcomes included bacterial counts and resistance patterns to antibiotics. RESULTS: Thirty-four patients were enrolled in the trial; 22 patients (mean age 77.22 years, 77.27% were men) completed the study. Cranberry was effective in reducing the number of symptomatic CA-UTIs in all patients (n=22). Resistance to antibiotics was reduced by 28%. Furthermore, colony counts were reduced by 58.65%. No subjects had adverse events while taking cranberry. CONCLUSIONS: The cranberry supplement reduced the number of symptomatic CA-UTIs, antibiotic resistances, and major causative organisms in this cohort. Larger, placebo-controlled studies are needed to further define the role of cranberry in CA-UTIs.

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.

BACKGROUND: Individuals with spinal cord injury (SCI) consume more dietary supplements than the general population. However, there is limited information regarding the clinical effectiveness of dietary supplements in SCI population. OBJECTIVE: To systematically review the effectiveness of dietary supplements for the prevention or treatment of health-related conditions associated with SCI. METHODS: Randomized or non-randomized controlled clinical trials were selected, comparing the effect of any dose and form of a dietary supplement (defined by the Dietary Supplement Health and Education Act), with either no treatment, placebo, or other medication. Data Sources included the Cochrane Database, DARE, LILACS, CINAHL, EMBASE, MEDLINE, OTSeeker, PEDro, PsycINFO, SpeechBITE, ScienceDirect, Scopus, clinicaltrials.gov, Google Scholar, and OpenGrey. Two reviewers independently classified articles from January 1970 through October 2015, and 18 articles were selected. RESULTS: Due to the heterogeneity of outcome measures across studies, a meta-analysis was not conducted. However, high-quality evidence showed that cranberry supplementation is not effective for prevention of urinary tract infections (UTIs) in SCI. Moderate-quality evidence supported a beneficial effect of vitamin D, alpha-lipoic acid, and omega-3 supplementation, although replication of results is needed. There were conflicting results for the effect of creatine supplementation on improvement of motor outcomes. Low-quality evidence does not permit assessment of the effectiveness of melatonin, whey protein, vitamin C, and Chinese herb in SCI. CONCLUSIONS: There is sufficient data suggesting that cranberry supplementation is ineffective for prevention of UTIs in individuals with SCI. There is insufficient data to support or refute the use of any other dietary supplement in individuals with SCI.

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.

Green tea (GT), cranberry (CR), and tart cherry extracts were evaluated for their ability to inhibit yeast alpha-glucosidase, relevant to glucose uptake. The total phenolic content (TPC), antioxidant activity, and in vitro inhibitory activity of yeast alpha-glucosidase were examined for the extracts in the present study. GT had higher TPC and antioxidant activity, but CR demonstrated a greater alpha-glucosidase inhibitory activity, on phenolic basis. CR was fractionated using LH-20 column chromatography into two fractions: 30% methanol (CME) and 70% acetone (CAE). TPC, antioxidant activity, and yeast alpha-glucosidase inhibitory activity were determined for the fractions. CAE had a greater TPC and antioxidant activity than CME, but the two fractions had a synergistic effect when inhibiting yeast alpha-glucosidase. Our findings suggest that CR has the greatest potential to possibly manage post-prandial blood glucose levels via the inhibition of alpha-glucosidase, and that the effect is through synergistic activity of the extract's phenolic compounds.