Several studies have shown the antimutagenic DNA protective functions of some naturally occurring phenolic phytochemicals. Emerging research also indicates that synergistic functionality of these phytochemicals in whole foods benefits the management of many diseases. This study investigated the potential antimutagenic properties of cranberry phenolics, ellagic acid (EA), rosmarinic acid (RA) and their synergistic interactions on enhancing the antimutagenic properties in Salmonella typhimurium tester system against the mutagens sodium azide and N-methyl-N'-nitro-N-nitrosoguanidine. The ability of these phytochemical treatments to protect oxidative damage to DNA was also investigated using the supercoiled DNA strand scission assay. The results showed that EA was most effective in inhibiting the mutations in S. typhimurium system, whereas RA and EA were equally effective in protecting the DNA from oxidative damage. In addition, the antimutagenic activity of cranberry powder (CP) made from juice extracts was significantly enhanced when 30% (w/w) of phenolics in CP was substituted with RA and EA, possibly because of synergistic redox modulation that can influence mutagen function. It was also suggested that the synergistic mixture of cranberry phenolics with RA could also be protecting the cell from mutations by modulating the DNA repair systems

Cranberry, the fresh or dried ripe fruit of Vaccinium macrocarpon Ait. (Ericaceae), is currently used as adjunct therapy for the prevention and symptomatic treatment of urinary tract infections. Data from clinical trials suggest that extracts of cranberry or cranberry juice reduce the bacterial load of E. coli and also suppress the inflammatory symptoms induced by E. coli infections. A methanol extract prepared from 10 kg of dehydrated cranberries did not directly inhibit the growth of E coli strains ATCC 700336 or ATCC 25922 in concentrations up to 256 mug/mL in vitro. However, the methanol extract (CR-ME) inhibited the activity of cyclooxygenase-2, with an IC(50) of 12.8 mug/mL. Moreover, CR-ME also inhibited the NF-kappabeta transcriptional activation in human T lymphocytes with an IC(50) of 19.4 mug/mL, and significantly (p 0.01) inhibited the release of interleukin (IL)-1beta, IL-6, IL-8 and tumor necrosis factor-alpha from E. coli lipopolysaccharide (LPS)-stimulated human peripheral blood mononuclear cells in vitro, at a concentration of 50 mug/mL. The extract had no effect on inducible nitric oxide synthase activity in the murine macrophage cell line RAW 264.7. The compounds responsible for this activity were identified using a novel LC-MS based assay as ursolic acid and ursolic acid derivatives. Taken together, these data suggest CR-ME and its constituent chemical compounds target specific pathways involved in E. coli-induced inflammation.

CONTEXT: Cranberry juice has long been recognized in folk medicine as a therapeutic agent, mainly in urinary tract infections. Its proposed mechanism of action is antiadhesion of bacteria.

OBJECTIVE: Investigation of the potential antiadhesion effect of nondialyzed material of cranberry (NDM) via its influence on secretion, gene expression, and promoter activity of the fructosyltransferase (FTF), which is among the extracellular enzymes associated with dental biofilm formation and pathogenesis of oral bacteria.

MAIN OUTCOME MEASURES: Secretion of FTF from Streptococcus mutans, in the presence of NDM, was measured by immunoblotting and confocal scanning laser microscopy. Its influence on ftf gene expression was determined by reverse transcription followed by real-time RT-PCR. The luciferase assay was used to detect bioluminescence expressed by the ftf promoter activity of bacteria exposed to NDM.

RESULTS: NDM at concentrations between 0.2/mL and 1mg/mL significantly (P.05) decreased secretion of extracellular FTF, as well as down-regulated ftf expression in a dose-dependent manner. NDM also markedly reduced the luciferase activity under the ftf promoter.

Cranberry juice has long been recognized in folk medicine as a therapeutic agent, mainly in urinary track infections. It acts as an antibiofilm agent against various pathogens. Quorum sensing is process where bacteria communicate with each other via signal molecules known as autoinducers. This process is strongly involved in various bacterial pathological and physiological pathways. Various strains of Vibrio harveyi bacteria were incubated with different concentrations of nondialyzable material of cranberry (NDM) with or without addition of exogenous autoinducer. Bioluminescence regulated by the autoinducers was measured in GENios reader. Effect of NDM alone or NDM supplemented with autoinducer on quorum sensing was determined as change in bioluminescence in each treated sample compared to appropriate control in every strain. Using model of V. harveyi, we found an inhibitory effect of cranberry constituents on bacterial signaling system. This effect was reversible, since exogenous autoinducer was able to recover bioluminescence which was decreased by NDM. We hypothesized that cranberry NDM interacts with V. harveyi quorum sensing by competition with autoinducer

PURPOSE: Vaccinium macrocarpon--the American cranberry--irreversibly inhibits the expression of P-fimbriae of E. coli. Further effects on the function and expression of P-fimbriae were studied by growing P-fimbriated E. coli in solid media laced with cranberry juice.

METHODS: Cranberry concentrate at pH 7.0 was added to CFA medium to a final concentration of 25%. E. coli strains JR1 and DS17 were plated on this medium with a plain CFA control and incubated at 37C. Cultures were tested for ability to agglutinate P-receptor specific beads. Bacteria were washed in PBS and agglutination retested. Cultures were also replated on plain CFA agar and rechecked for their ability to agglutinate. Transmission electron micrographs were performed on positive control and test bacteria.

RESULTS: For E. coli strain JR1, P-fimbrial agglutination was inhibited after the third plating. DS17 was fully inhibited after the second plating. Washing in PBS did not affect agglutination, but replating on CFA agar allowed agglutination to recur. Electron micrographic study of control populations confirmed fimbriae. Fully inhibited bacteria had a 100% reduction in expression of fimbriae. Additionally, inhibited bacteria showed cellular elongation.

CONCLUSIONS: Cranberry juice irreversibly inhibits P-fimbriae. Electron micrographic evidence suggests that cranberry juice acts on the cell wall preventing proper attachment of the fimbrial subunits or as a genetic control preventing the expression of normal fimbrial subunits or both.

Because previous studies have shown that a high molecular mass constituent of cranberry juice inhibited adhesion of Escherichia coli to epithelial cells and coaggregation of oral bacteria, we have examined its effect on the adhesion of Helicobacter pylori to immobilized human mucus and to erythrocytes. We employed three strains of H. pylori all of which bound to the mucus and agglutinated human erythrocytes via a sialic acid-specific adhesin. The results showed that a high molecular mass constituent derived from cranberry juice inhibits the sialic acid-specific adhesion of H. pylori to human gastric mucus and to human erythrocytes.

Bacterial surface properties, such as electrostatic potential play an important role in the bacterial adhesion process, which is widely considered as the first step leading to infections. Cranberry juice and its compound A-type proanthocyanidins (PACs) were used to treat two isogenic E. coli strains and human uroepithelial cells and the zeta potentials were measured at several cranberry juice or PACs concentrations. P fimbriae were shown to be slightly positively charged, which helps bacteria adhere onto mammalian cells. PACs significantly decreased the bacterial zeta potentials from -15.6 ± 0.9 mV to -41.5 ± 0.7 mV, which increased the electrostatic repulsion forces to mammalian cells. Cranberry juice treatment did not change bacterial zeta potentials significantly, ranging from -14.9 ± 1.8 mV to -16.3 ± 0.8 mV. The abundance of other compounds in cranberry juice may have blocked the influence of PACs, considering the relatively small proportion of PACs in cranberry juice.

An extract from fresh cranberries was shown to decrease the strength of attachment of Escherichia coli to glass coverslips when incubated together for 2 h. Pre-conditioning of the surface prior to biofilm formation also significantly weakened the strength of attached cells.

BACKGROUND: The inhibition of Escherichia coli growth in the presence of Vaccinium macrocarpon has been extensively described; however, the mechanisms of this activity are not well characterized.

FINDINGS: Here, E. coli was grown in media spiked with cranberry juice. The growth rate and media pH were monitored over more than 300 generations. The pH of the growth media was found to decrease during cell growth. This result was unique to media spiked with cranberry juice and was not reproduced through the addition of sugars, proanthocyanidins, or metal chelators to growth media.

CONCLUSION: This study demonstrated that factors other than sugars or proanthocyanidins in cranberry juice result in acidification of the growth media. Further studies are necessary for a complete understanding of the antimicrobial activity of cranberry products.

An ethanolic extract of Cranberry exerted a significant antimicrobial effect on Saccharomyces bayanus and Pseudomonas fluorescens. The antimicrobial properties of cranberries were due to a number of factors. First, the low pH (2.6) inhibited many microorganisms per se, and its effect on the dissociation of benzoic acid made the inhibition more drastic. Secondly, after raising the pH to 5.2, cranberry juice still did not support the growth of S. bayanus. Growth did occur at pH 5.2 after 0.3% yeast nitrogen base was added. Thirdly, proanthocyanidins and flavonols were found to be the major microbial inhibitors other than benzoic acid. The results showed that proanthocyanidins provided 21.3% of the inhibition, the flavonols 18.5% and benzoic acid 15.6%.