This study was designed to unravel the role of Lactobacillus rhamnosus in the bioconversion of cranberry proanthocyanidins and cytotoxicity of resulting metabolites to hepatocellular carcinoma HepG2 cells. Crude (CR) and flavonol+dihydrochalcone- (FL+DHC-), anthocyanin- (AN-), proanthocyanidin- (PR-), and phenolic acid+catechin- (PA+C-) rich fractions were subjected to fermentation with L. rhamnosus at 37degreeC for 12, 24, and 48 h under anaerobic conditions. The major metabolites produced by bioconversion of polyphenols were 4-hydroxyphenylacetic acid, 3-(4-hydroxyphenyl)propionic acid, hydrocinnamic acid, catechol, and pyrogallol. Furthermore, cytotoxicity of the biotransformed extracts was compared to their parent extracts using human hepatocellular carcinoma HepG2 cells. The results showed that PR-biotransformed extract completely inhibited HepG2 cell proliferation in a dose- and time-dependent manner with IC50 values of 47.8 and 20.1 mug/mL at 24 and 48 h, respectively. An insight into the molecular mechanisms involved revealed that the cytotoxic effects of PR at 24 h incubation were mitochondria-controlled and not by proapoptotic caspase-3/7 dependent. The present findings suggest that the application of a bioconversion process using probiotic bacteria can enhance the pharmacological activities of cranberry proanthocyanidins by generating additional biologically active metabolites.

In the present study, unfermented and fermented cranberry juice in combination with the Antibiotics vancomycin and tigecycline were tested for their antimicrobial activity. Cranberry juice was fermented with a recently isolated potentially probiotic Lactobacillus paracasei K5. The tested strains selected for this purpose were Enterococcus faecalis, E. faecium, Enterobacter cloacae and Staphylococcus aureus. The methods followed were the determination of zones inhibition, Minimum Inhibitory Concentration (MIC) and Fractional Inhibitory Concentration Index (FICI). Tigecycline together with fermented juice exhibited larger Zones of Inhibition (ZOI) in strains of E. faecium (65 +/- 4.8 mm) compared to the respective ZOI with tigecycline and unfermented juice (no zone). The same outcome was also obtained with E. cloacae. Vancomycin together with fermented juice exhibited larger ZOI in strains of E. faecium (28 +/- 2.2 mm) compared to the respective ZOI with vancomycin and unfermented juice (24 +/- 2.3 mm). The lowest MIC values were recorded when tigecycline was combined with fermented cranberry juice against S. aureus strains, followed by the same combination of juice and antibiotic against E. cloacae strains. FICI revealed synergistic effects between fermented juice and tigecycline against a strain of E. faecium (A2020) and a strain of E. faecalis (A1940). Such effects were also observed in the case of fermented juice in combination with vancomycin against a strain of S. aureus (S18), as well as between fermented juice and tigecycline against E. cloacae (E1005 and E1007) strains. The results indicate that the antibacterial activity of juice fermented with the potentially probiotic L. paracasei K5 may be due to synergistic effects between some end fermentation products and the antibiotic agents examined.

BACKGROUND & AIMS: African American and European American individuals have a similar prevalence of gastroesophageal reflux disease (GERD), yet esophageal adenocarcinoma (EAC) disproportionately affects European American individuals. We investigated whether the esophageal squamous mucosa of African American individuals has features that protect against GERD-induced damage, compared with European American individuals. METHODS: We performed transcriptional profile analysis of esophageal squamous mucosa tissues from 20 African American and 20 European American individuals (24 with no disease and 16 with Barrett's esophagus and/or EAC). We confirmed our findings in a cohort of 56 patients and analyzed DNA samples from patients to identify associated variants. Observations were validated using matched genomic sequence and expression data from lymphoblasts from the 1000 Genomes Project. A panel of esophageal samples from African American and European American subjects was used to confirm allele-related differences in protein levels. The esophageal squamous-derived cell line Het-1A and a rat esophagogastroduodenal anastomosis model for reflux-generated esophageal damage were used to investigate the effects of the DNA-damaging agent cumene-hydroperoxide (cum-OOH) and a chemopreventive cranberry proanthocyanidin (C-PAC) extract, respectively, on levels of protein and messenger RNA (mRNA).RESULTS: We found significantly higher levels of glutathione S-transferase theta 2 (GSTT2) mRNA in squamous mucosa from African American compared with European American individuals and associated these with variants within the GSTT2 locus in African American individuals. We confirmed that 2 previously identified genomic variants at the GSTT2 locus, a 37-kb deletion and a 17-bp promoter duplication, reduce expression of GSTT2 in tissues from European American individuals. The nonduplicated 17-bp promoter was more common in tissue samples from populations of African descendant. GSTT2 protected Het-1A esophageal squamous cells from cum-OOH-induced DNA damage. Addition of C-PAC increased GSTT2 expression in Het-1A cells incubated with cum-OOH and in rats with reflux-induced esophageal damage. C-PAC also reduced levels of DNA damage in reflux-exposed rat esophagi, as observed by reduced levels of phospho-H2A histone family member X.CONCLUSIONS: We found GSTT2 to protect esophageal squamous cells against DNA damage from genotoxic stress and that GSTT2 expression can be induced by C-PAC. Increased levels of GSTT2 in esophageal tissues of African American individuals might protect them from GERD-induced damage and contribute to the low incidence of EAC in this population.

Patients with chronic kidney disease (CKD) present many complications that potentially could be linked to increased cardiovascular mortality such as inflammation, oxidative stress, cellular senescence and gut dysbiosis. There is growing evidence suggesting that nutritional strategies may reduce some of these complications. Clinical studies suggest that supplementation of cranberries may have beneficial effects on human health such as prevention of urinary tract infections. More recently, the anti-inflammatory and anti-oxidant effects as well as modulation of gut microbiota provided by cranberry phytochemicals have drawn more attention. A better understanding of possible effects and mechanisms of action of cranberry supplementation in humans could inform researchers about warranted future directions for clinical studies targeting these complications in CKD patients by applying nutritional strategies involving cranberry supplementation.

Alcoholic steatohepatitis is an important medical problem but its effective therapies are still not available. Plant polyphenols are widely used for prevention of toxic liver damages. The aim of the study was to evaluate the hepatoprotective mechanism(s) of a cranberry peel polyphenol-rich extract, focusing on the effects of the polyphenols on the mitochondrial function.The main components of cranberry peel phenolic compounds were anthocyanins, flavan-3-ols, procyanidins, flavonols, phenolic acids, as was detected using UHPLC-ESI-QTOF-MS. The treatment of rats receiving ethanol (4 g/kg bw, 8 weeks) with cranberry polyphenols (daily, 4 mg/kg bw) partially prevented alcoholic liver damage, ameliorating steatosis and inflammatory signs in the liver, decreasing serum and liver triglyceride contents, ALT and AST activities, as well as diminishing TNFα and TGFβ levels in serum. The polyphenols inhibited Ca2+ - induced mitochondrial permeability transition, free radical generation in mitochondria during intoxication. The polyphenols (25 µg/ml) prevented mitochondrial oxidative impairments in vitro. In conclusion, the cranberry peel polyphenols with antioxidant properties exerted a hepatoprotective and anti-inflammatory effects in the model of alcoholic steatohepatitis via prevention of liver mitochondria dysfunction.

Obesity is characterized by abnormal or excessive fat accumulation, which leads to the development of metabolic syndrome. Because oxidative stress is increased in obesity, antioxidants are regarded as suitable agents for preventing metabolic syndrome. Here, we examined the impact of cranberry, which contains various antioxidants, on metabolic profiles, including that during the progression of non-alcoholic fatty liver disease (NAFLD), in high-fat diet (HFD)-fed C57BL/6 mice. We observed that oxidative stress was diminished in mice that were fed HFD diets supplemented with 1 and 5% cranberry powder as compared with that in HFD-fed control mice. Notably, from 1 week after beginning the diets to the end of the study, the body weight of mice in the cranberry-treatment groups was significantly lower than that of mice in the HFD-fed control group; during the early treatment phase, cranberry suppressed the elevation of serum triglycerides; and adipocytes in the adipose tissues of cranberry-supplemented-HFD-fed mice were smaller than these cells in HFD-fed control mice. Lastly, we examined the effect of cranberry on NAFLD, which is one of the manifestations of metabolic syndrome in the liver. Histological analysis of the liver revealed that lipid-droplet formation and hepatocyte ballooning, which are key NAFLD characteristics, were both drastically decreased in cranberry-supplemented-HFD-fed mice relative to the levels in HFD-fed control mice. Our results suggest that cranberry ameliorates HFD-induced metabolic disturbances, particularly during the early treatment stage, and exhibits considerable potential for preventing the progression of NAFLD.

Cranberry has been widely utilized as a popular botanical dietary supplement to prevent urinary tract infection. The study aims to evaluate the enhanced bactericidal activities of cranberry against uropathogenic Escherichia coli (UPEC) by adding a small quantity of naturally derived antimicrobials. The antibacterial effect was examined with cranberry extract alone (15 and 20%), three kinds of medium-chain fatty acids alone (caprylic, capric, and lauric acid; 0.05–1.0 mM), essential oils alone (carvacrol and thymol; 0.5–1.0 mM), and cranberry extract containing medium-chain fatty acids or essential oils at 37 °C for 1 min. The survivors were remarkably reduced with cranberry extract containing any of the antimicrobials. For example, cranberry extract (15 and 20%) with 1.0 mM of each caprylic acid, lauric acid, and carvacrol resulted in the complete eradication of UPEC (7.55 log reduction). Flow cytometry analysis of UPEC cells exposed to combined treatment showed clear membrane disruption and cell death (>95% of damage). Adding antimicrobials to cranberry extract did not affect (P > 0.05) the characteristics of the cranberry extract (Color, °Brix, pH). The present method may be more acceptable to consumers, who tend to avoid products containing synthetic chemicals and prefer the use of natural agents.

Bioactive polyphenol components of cranberry (Vaccinium macrocarpon) are known to have virulence attenuating effects against several cariogenic virulence properties responsible for dental caries pathogenesis. In particular, cranberry A-type proanthocyanidins and flavonols have demonstrated potent inhibitory effects against cariogenic virulence targets such as bacterial acidogenicity, aciduricity, glucan synthesis, and hydrophobicity. Cranberry phenols have the ability to disrupt these cariogenic virulence properties without being bactericidal, a key quality essential for retaining the benefits of the symbiotic resident oral microbiome and preventing the emergence of resistant microbes. This review discusses the cariostatic mechanisms of specific cranberry phytochemicals and their potential use as therapeutic agents against cariogenic bacteria in the prevention and control of dental caries.

Cranberry proanthocyanidins (PACs) can be partitioned into soluble PACs, which are extracted with solvents, and insoluble PACs, which remain associated with fibers and proteins after extraction. Most research on cranberry products only quantifies soluble PACs because proper standards for quantifying insoluble PACs are lacking. In this study, we evaluated the ability of a cranberry PAC (c-PAC) standard, reflective of the structural heterogeneity of PACs found in cranberry fruit, to quantify insoluble PACs by the butanol-hydrochloric acid (BuOH-HCl) method. For the first time, a c-PAC standard enabled conversion of BuOH-HCl absorbance values (550 nm) to a weight (milligram) basis, allowing for quantification of insoluble PACs in cranberries. The use of the c-PAC reference standard for sequential analysis of soluble PACs by the method of 4-(dimethylamino)cinnamaldehyde and insoluble PACs by the method of BuOH-HCl provides analytical tools for the standardization of cranberry-based ingredients.

OBJECTIVE: To investigate the effect of cranberry extracts on saliva-derived polymicrobial biofilms with regards to biofilm biomass, acidogenicity, exopolysaccharide (EPS)/microbial biovolumes, colony forming unit (CFU) counts, and the relative abundance of specific caries- and health-associated bacteria.METHODS: Saliva-derived polymicrobial biofilms were grown for 96 h in a cariogenic environment and treated for 2 min every 12 h over the entire biofilm growth period with 500 mug/mL cranberry extract or vehicle control. The effect of the cranberry extract on biofilm behaviour was evaluated using different assays and its influence on key cariogenic and health-associated bacterial populations was assessed with a microarray real-time quantitative PCR method.RESULTS: Cranberry-treated biofilms showed significant drops in biomass (38% reduction, P < 0.001), acidogenicity (44% reduction, P < 0.001), EPS/microbial biovolume ratios (P = 0.033), and CFU counts (51% reduction, P = 0.001). Furthermore, the cranberry extracts effected a significantly lower relative abundance of caries-associated Streptococcus sobrinus (fold change 0.004, P = 0.002) and Provotella denticola (0.002, P < 0.001), and a significantly higher relative abundance of the health-associated Streptococcus sanguinis (fold change 90.715, P = 0.001).CONCLUSIONS: The cranberry extract lowered biofilm biomass, acidogenicity, EPS/microbial biovolumes, CFU counts, and modulated a beneficial microbial ecological change in saliva-derived polymicrobial biofilms.