Breast cancer is the most common cancer and a major cause of death in women. The present study was designed to evaluate the antioxidant and anticancer potential of cranberry extract against N-methyl-N-nitrosourea (MNU) induced mammary carcinoma in rats. The tumor was induced in Female virgin rats of age 50 days by single dose of MNU (50mg/kg.b.w i.p.). After 85 days; all rats developed at least one tumor. Animals were treated with cranberry extract (400 and 600 mg/kg.b.w.orally) and tamoxifen (2mg/kg.b.w. i.p) for 4 weeks (from day 86 to day 113). MNU treatment resulted in a significant decrease (p < 0.05) in blood hemoglobin (Hb), red blood cells (RBC), platelets (PLTs) as well as blood, liver and breast catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD). However, MNU treatment resulted in a significant increase in White blood cells (WBC) as well as plasma, liver and mammary tissue gamma glutamyl transferase (GGT), lactate dehydrogenase (LDH), hexosamine, sialic acid and thiobarbituric acid reactive substances (TBARs). Upon administration of the cranberry extract, the levels of WBC, GGT, LDH, hexosamine, sialic acid, TBARs, Hb, RBC, PLTs, CAT, GPx and SOD were significantly normalized. Histopathological changes also confirmed the formation of tumor tubules and neovascularization after the MNU treatment. Cranberry extract administration significantly reduces the growth of MNU-induced mammary tumors, and therefore has strong potential as a useful therapeutic regimen for inhibiting breast cancer development. Comparing the beneficial effect of cranberry extract with that of MNU-induced breast cancer, cranberry extract showed antitumor and antioxidant activity indicated by the measured biochemical parameters and the histopathological examination of mammary tissue. The results of the present study indicate that cranberry extract possesses strong anticancer effects through its role in modulating glycoprotein components and the levels of oxidative stress biomarkers. Cranberry exerted a stronger anticancer effect at the dosage of 600 mg/kg body weight than at dosage 400 mg/kg body weight.

Background: Cranberry pomace (CP), an underutilized by-product from juice processing, contains a wide range of biologically active compounds that can be recovered and used in a variety of applications in functional foods and nutraceuticals. Methods: In this study, analytical chemical techniques such as solvent extractions and characterization of extracts in respect with their phenolic content were performed using ultra-high performance liquid chromatography mass spectrometry (UPLC-MS) and spectrophotometry. Crude CP extract and its phenolic acids, flavonols, anthocyanins and proanthocyanidins–rich fractions were then evaluated for their anti-oxidant capacity, tyrosinase inhibitory activity, and anti-proliferation activity against hepatocellular carcinoma HepG2 cells. Results: On a dry weight basis, the different CP fractions contained seven major anthocyanins (0.1-125 mg/g), six major phenolic acids (0.8-31 mg/g), seven flavonols (1-126 mg/g) and five flavan-3-ols (0.1-12 mg/g). Fractions rich in flavonols exhibited the most potent antioxidant capacities with ferric ion reducing antioxidant power values of 1.8-1.9 mmole/g and 2, 2-diphenyl-1-picrylhydrazyl radical scavenging IC50 values of 15.1-15.2 mg/L respectively. On the other hand, fractions rich in phenolic acids and flavan-3-ol monomers demonstrated the most potent anti-tyrosinase activity (IC50=6.1-6.2 mg/L) and anti-proliferative activity (IC50=7.8-15.8 mg/L). Generally, all the fractions exhibited a dose-response relationship in the selected biological activity assays.Conclusion: This study suggests an effective utilization of CP to obtain biologically active fractions with potential to be used in functional foods and nutraceuticals designed for the prevention of chronic diseases associated with oxidative stress.

Cranberries and probiotics are individually considered as functional foods. This study evaluated the potential synergy between bioactive proanthocyanidins (c-PAC) derived from cranberries and probiotics on reducing the invasiveness of extra-intestinal pathogenic Escherichia coli (ExPEC) in a cell culture model. ExPEC can be a component of the gut microbiota in healthy individuals, and reducing the invasiveness of ExPEC is a potential means to lessen the risk of subsequent urinary tract infections (UTI), the most common bacterial infections in women. c-PAC (>92% A-type) concentrations greater than 36 micro g c-PAC/mL significantly (p<0.05) reduced ExPEC invasion, and was not inhibited by the presence of probiotics. Scanning electron microscopy suggests that the mechanism by which c-PAC prevent ExPEC invasion is by cross-linking surface virulence factors. A probiotic blend also significantly reduced invasion, albeit via a different mechanism. This study demonstrated the potential benefit of combining functional A-type c-PAC components in cranberry foods with probiotics.

Background: Catheter-associated urinary tract infections (CAUTIs) represent over 30% of hospital-acquired infections with an annual incidence of 560,000 CAUTIs per year in the United States. An estimated 13,000 deaths are attributable to CAUTIs annually. Standard prevention strategies frequently fail to eliminate CAUTI in intensive care units. The effectiveness of a hospital-based program of cranberry products (CP) and meatal antimicrobials to prevent CAUTI in a heterogeneous ICU population has not been evaluated. Methods: Data of Foley days and incidence of CAUTI in the Critical Care Unit (CCU) and the general wards (GW) in a single 245-bed suburban medical center were collected as a part of routine infection control surveillance. Standard CAUTI prevention bundles were applied throughout the hospital in 2009. In May 2012 an intervention of applying Bacitracin ointment to the urinary meatus-Foley junction and oral cranberry juice or tablets was started only in the CCU. A retrospective review of the data collected before and after the intervention in both the GW and CCU was completed. Results: Prior to the QI intervention in May 2012, average CAUTI rates were 2.8 CAUTIs per 1000 catheter days (CI 0.26-1.89) in the CCU and 1.6 CAUTIs per 1000 catheter days (CI 0.71-4.97) on the GW (p = 0.28). After the intervention, the average number of CAUTIs/1000 days in the CCU was 0, which was significantly different from the average of 1.52 CAUTIs/1000 days (CI 0.78-2.26) on the GW (p < 0.001). Conclusion: Our data indicate that the addition of cranberry-containing products and antimicrobial meatal care may further reduce incidence of CAUTI when added to standard recommendations. Further research will be necessary to determine if these interventions could be effective in a wider population.

Cranberry products have long been used to treat urinary tract infections. It is believed that the A-type proanthocyanidins in cranberries contribute to this function. Peanut is one of the other, few food sources that primarily contain A-type proanthocyanidins. The skin on the outside of the peanut kernels (testa), which is treated as an agriculture waste product, contains high levels of A-type proanthocyanidins. In this study, an HPLC diol column separation method and MALDI-TOF MS were used to characterize and compare the proanthocyanidin compositions of peanut skins and cranberries. MALDI-TOF MS in linear mode was able to detect a group of proanthocyanidins with DP (degree of polymerization) 10 in peanut skin extract, but was only able to detect DP 8 in cranberry extract.The reflectron mode showed clusters of clear narrow peaks at DP 7 in peanut skin extract, while the highest DP resolved for cranberry extract was only 3 in reflectron mode. This might be due to the low response intensity of the cranberry samples with the current cleanup method and the matrix. Based on the resolved peaks in reflectron mode, peanut skins and cranberries have similar proanthocyanidins composition; they contain both A-type and B-type proanthocyanidins, with the A-type being predominant. This result may inspire future studies on the comparison of biological functions between peanut skins and cranberries and further comparison of their polymeric proanthocyanidin composition.

Cranberries are rich in bioactive constituents reported to influence a variety of health benefits, ranging from improved immune function and decreased infections to reduced cardiovascular disease and more recently cancer inhibition. A review of cranberry research targeting cancer revealed positive effects of cranberries or cranberry derived constituents against 17 different cancers utilizing a variety of in vitro techniques, whereas in vivo studies supported the inhibitory action of cranberries toward cancers of the esophagus, stomach, colon, bladder, prostate, glioblastoma and lymphoma. Mechanisms of cranberry-linked cancer inhibition include cellular death induction via apoptosis, necrosis and autophagy; reduction of cellular proliferation; alterations in reactive oxygen species; and modification of cytokine and signal transduction pathways. Given the emerging positive preclinical effects of cranberries, future clinical directions targeting cancer or premalignancy in high risk cohorts should be considered.

Cranberry (Vaccinium macrocarpon) consumption has been associated with health beneficial effects. Nonalcoholic fatty liver disease (NAFLD) is a comorbidity of obesity. In the present study, we investigated the effect of a polyphenol-rich cranberry extract (CBE) on hepatic inflammation in high fat (HF)-fed obese C57BL/6J mice. Following dietary treatment with 0.8% CBE for 10 weeks, we observed no change in body weight or visceral fat mass in CBE-supplemented mice compared to HF-fed control mice. We did observe a significant decrease in plasma alanine aminotransferase (31%) and histological severity of NAFLD (33% decrease in area of involvement, 29% decrease in lipid droplet size) compared to HF-fed controls. Hepatic protein levels of tumor necrosis factor alpha and C-C chemokine ligand 2 were reduced by 28% and 19%, respectively, following CBE supplementation. CBE significantly decreased hepatic mRNA levels of toll-like receptor 4 (TLR4, 63%) and nuclear factor kappa B (NF kappa B, 24%), as well as a number of genes related to the nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing 3 inflammasome. In conclusion, CBE reduced NAFLD and hepatic inflammation in HF-fed obese C57BL/6J mice. These effects appear to be related to mitigation of TLR4-NF kappa B related signaling; however, further studies into the underlying mechanisms of these hepatoprotective effects are needed.

A growing body of evidence suggests that nutraceuticals with prolongevity properties may delay the onset of Alzheimer's disease (AD). We recently demonstrated that a proanthocyanidins-standardized cranberry extract has properties that prolong life span and promote innate immunity in Caenorhabditis elegans. In this article, we report that supplementation of this cranberry extract delayed A beta toxicity-triggered body paralysis in the C. elegans AD model. Genetic analyses indicated that the cranberry-mediated A beta toxicity alleviation required heat shock transcription factor (HSF)-1 rather than DAF-16 and SKN-1. Moreover, cranberry supplementation increased the transactivity of HSF-1 in an IIS-dependent manner. Further studies found that the cranberry extract relies on HSF-1 to significantly enhance the solubility of proteins in aged worms, implying an improved proteostasis in AD worms. Considering that HSF-1 plays a pivotal role in maintaining proteostasis, our results suggest that cranberry maintains the function of proteostasis through HSF-1, thereby protecting C. elegans against A beta toxicity. Together, our findings elucidated the mechanism whereby cranberry attenuated A beta toxicity in C. elegans and stressed the significance of proteostasis in the prevention of age-related diseases from a practical point of view.

Background and Objectives. Recently, we described an inverse association between cranberry supplementation and serum prostate specific antigen (PSA) in patients with negative biopsy for prostate cancer (PCa) and chronic nonbacterial prostatitis. This double blind placebo controlled study evaluates the effects of cranberry consumption on PSA values and other markers in men with PCa before radical prostatectomy. Methods: Prior to surgery, 64 patients with prostate cancer were randomized to a cranberry or placebo group. The cranberry group (n=32) received a mean 30 days of 1500 mg cranberry fruit powder. The control group (n=32) took a similar amount of placebo. Selected blood/urine markers as well as free and total phenolics in urine were measured at baseline and on the day of surgery in both groups. Prostate tissue markers were evaluated after surgery. Results: The serum PSA significantly decreased by 22.5% in the cranberry arm (n=31, P<0.05). A trend to down-regulation of urinary beta-microseminoprotein (MSMB) and serum gamma-glutamyltranspeptidase, as well as upregulation of IGF-1 was found after cranberry supplementation. There were no changes in prostate tissue markers or, composition and concentration of phenolics in urine. Conclusions: Daily consumption of a powdered cranberry fruit lowered serum PSA in patients with prostate cancer. The whole fruit contains constituents that may regulate the expression of androgen-responsive genes.

Background: Due to the higher susceptibility of metabolic syndrome (MS)-afflicted patients to different metabolic abnormalities, treatment programs are vital parts of MS management. One of the possible adjunctive therapies is taking cranberry supplements as important sources of polyphenols that bear antioxidative and health-promoting properties.Objectives: The aim of this study was to evaluate the effect of cranberry extract on some components of metabolic syndrome.Patients and Methods: In a randomized, double-blind placebo-controlled clinical trial, 48 obese and overweight females diagnosed with MS were assigned into two groups to receive cranberry supplement or placebo for an eight-week period. Serum glucose, lipoproteins, inflammatory markers and blood pressure were evaluated at the baseline and at the end of the treatment phase.Results: Cranberry supplements had no effect on any of the variables including glucose, insulin, malondialdehyde (MDA), high-sensitive C-reactive protein (hs-CRP), interleukin-6 (IL-6), and blood pressure, except for high-density lipoprotein cholesterol (HDL-c), which significantly increased (P < 0.05) at the eighth-week period compared with the placebo samples.Conclusions: The results of the present study revealed that cranberry supplement might only ameliorate low HDL-c as a component of metabolic syndrome, and not the other risk factors of MS.