The antimicrobial properties of the American cranberry were studied against Escherichia coli O157:H7, Listeria monocytogenes, and Lactobacillus rhamnosus to determine the effects on growth inhibition, membrane permeability, and injury. Cranberry powder was separated using a C-18 Sep-Pak cartridge into sugars plus organic acids (F1), monomeric phenolics (F2), and anthocyanins plus proanthocyanidins (F3). Fraction 3 was further separated into anthocyanins (F4) and proanthocyanidins (F5) using an LH-20 Sephadex column. Each fraction was diluted in the brain heart infusion (BHI) broth to determine the minimum inhibitory/bactericidal concentrations (MIC/MBC). L. monocytogenes was the most susceptible to cranberry fraction treatment with the lowest MIC/MBC for each treatment, followed by E. coli O157:H7 and L. rhamnosus. Membrane permeability and potential was studied using LIVE/DEAD viability assay and using Bis (1, 3-dibutylbarbituric acid) trimethine oxonol (DiBAC4), respectively. L. rhamnosus demonstrated the highest permeability followed by E. coli O157:H7, and L. monocytogenes. L. rhamnosus demonstrated the highest recovery followed by E. coli O157:H7, and L. monocytogenes. Each cranberry fraction demonstrated membrane hyperpolarization at their native pH, while F2, F3, and F5 demonstrated membrane depolarization at neutral pH. With this knowledge cranberry compounds may be used to prevent maladies and potentially substitute for synthetic preservatives and antibiotics.

Cranberry A-type proanthocyanidins (PACs) have been recognized for their inhibitory activity against bacterial adhesion and biofilm-derived infections. However, the precise identification of the specific classes of degree-of-polymerization (DP) conferring PACs bioactivity remains a major challenge owing to the complex chemistry of these flavonoids. In this study, chemically characterized cranberries were used in a multistep separation and structure-determination technique to isolate A-type PAC oligomers of defined DP. The influences of PACs on the 3D architecture of biofilms and Streptococcus mutans-transcriptome responses within biofilms were investigated. Treatment regimens that simulated topical exposures experienced clinically (twice-daily, 60s each) were used over a saliva-coated hydroxyapatite biofilm model. Biofilm accumulation was impaired, while specific genes involved in the adhesion of bacteria, acid stress tolerance, and glycolysis were affected by the topical treatments (vs the vehicle-control). Genes (rmpC, mepA, sdcBB, and gbpC) associated with sucrose-dependent binding of bacteria were repressed by PACs. PACs of DP 4 and particularly DP 8 to 13 were the most effective in disrupting bacterial adhesion to glucan-coated apatitic surface (>85% inhibition vs vehicle control), and gene expression (eg rmpC). This study identified putative molecular targets of A-type cranberry PACs in S. mutans while demonstrating that PAC oligomers with a specific DP may be effective in disrupting the assembly of cariogenic biofilms.

A method to deconvolute overlapping isotope patterns in positive mode matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was developed to determine ratios of A- to B-type interflavan bonds in proanthocyanidins that were isolated from cranberry (Vaccinium macrocarpon, Ait.) press cake (c-PAC). Precision and accuracy was validated for binary mixtures of procyanidins A2 and B2. Deconvolution of c-PAC spectra indicated that oligomers with one or more A-type interflavan bonds occur in a higher proportion than oligomers with all B-type interflavan bonds. c-PAC with at least one A-type bond accounted for more than 91% of the oligomers between trimers and undecamers. The c-PAC isotope patterns are highly repeatable, suggesting that the method can be applied to authentication, standardization and efficacy of cranberry products in relationship to urinary tract health. This is the first time MALDI-TOF MS has been used for estimating ratios of A- to B-type bonds in PAC.

BACKGROUND: Recurrent urinary tract infections (UTIs) increase mortality and reduce graft survival after renal transplantation. Strategies to prevent recurrent UTIs include L-methionine, cranberry juice, and antibiotics. Data on the efficacy of cranberry and L-methionine, however, are controversial in the general population; there are few data in renal transplant recipients.
METHODS: We performed a retrospective analysis of 82 transplant recipients with recurrent UTIs, who underwent prophylaxis with cranberry juice (2 x 50 mL/d, n = 39, 47.6%), or L-methionine (3 x 500 mg/d, n = 25, 30.5%), or both modalities (n = 18, 21.9%). Thirty patients without prophylaxis served as controls. We analyzed symptoms, pyuria/nitrituria, and incidence of UTI events during 1 year before versus after initiation of prophylaxis.
RESULTS: Prophylaxis highly significantly decreased the annual UTI incidence by 58.3% (P .001) in the study population with no change in the control group (P = .85); in addition, 53.7% of symptomatic patients reported relief of symptoms and pyuria/nitrituria disappeared in 42.4% of the dipstick-positive patients (P .001 each). Cranberry reduced the annual number of UTI episodes by 63.9% from 3.6 +/- 1.4 to 1.3 +/- 1.3/year (P .001) and L-methionine by 48.7% from 3.9 +/- 1.8 to 2.0 +/- 1.3/year (P .001).
CONCLUSION: Cranberry juice and L-methionine successfully reduced the incidence of UTI after renal transplantation.

Epidemiological evidence supports inverse associations between fruit and vegetable intake and incidence of
cardiovascular disease and neurodegeneration. Dietary botanicals with salient health benefits include berries and leafy vegetables. Molecular pharmacology research has ascribed these benefits primarily to phenolic constituents and antioxidant activity. The current investigation sought to eluicidate pharmacologic activity of two novel preparations of berry and spinach extracts in vitro. Blueberry and cranberry exhibited the greatest antioxidant activity. In a dose-dependent manner, a proprietary mixture of cranberry and blueberry extracts inhibited inhibitor of jB kinase b, a central node in inflammatory signal transduction. A proprietary mixture of blueberry, strawberry, and spinach extracts inhibited prolyl endopeptidase, a regulator
of central neuropeptide stability and an emerging therapeutic target in neurology and psychiatry. These results indicate specific molecular targets of blended dietary plants with potential relevance to inflammation and neurological health.

Diets rich in fruit and vegetables promote health and delay the onset of diseases associated with oxidative stress. The benefit, especially of different berries, has been largely attributed to their content of numerous phytochemicals, and their effects in terms of antioxidant capacity are often evaluated chemically by different methods. We have instead used a highly relevant biological model, a modified CAP-e assay (Cell-based Antioxidant Protection in erythrocytes), to evaluate bioefficacy of antioxidants in Swedish berries. Extracts of twelve fruit and berries were analysed both by chemical and biological analyses: apple (Malus domestica, peel), bilberry (Vaccinium myrtillus), black currant (Ribes nigrum), purple chokeberry (Aronia x prunifolia), cranberry (Vaccinium macrocarpon), elderberry (Sambucus nigra), lingonberry (Vaccinium vitis-idaea), raspberry (Rubus idaeus), rose hips (Rosa spp.), sea buckthorn (Hippohae rhamnoides), sloe (Prunus spinosa) and strawberry (Fragaria x ananassa). Purple chokeberry, sloe and rose hips showed high antioxidant capacity in the chemical assays. Rose hips showed the highest degree of antioxidant protection also in the biological model, however, chokeberry and sloe showed medium or low protection. Furthermore, strawberry showed overall high protection in the biological assay but low antioxidant capacity in the chemical assays. The chemical and biological models showed different results and future studies of the biological model and in vivo situations are necessary.

Lactobacillus plantarum IFPL935 was incubated with individual monomeric flavan-3-ols and dimeric A- and B-type procyanidins to identify new metabolites and to determine the effect of compound structural features on bacterial growth and catabolism. Complex extracts rich in A-type proanthocyanidins and phenolic acids from cranberry were also tested. The results showed that L. plantarum IFPL935 exhibited higher resistance to nongalloylated monomeric flavan-3-ols, A-type dimeric procyanidins, and cranberry extract than to (−)-epicatechin-3-O-gallate and B-type dimeric procyanidins. Despite these findings, the strain was capable of rapidly degrading (−)-epicatechin-3-O-gallate, but not A- or B-type dimeric procyanidins. However, it
was able to produce large changes in the phenolic profile of the cranberry extract mainly due to the catabolism of
hydroxycinnamic and hydroxybenzoic acids. Of most relevance was the fact that L. plantarum IFPL935 cleaved the heterocyclic ring of monomeric flavan-3-ols, giving rise to 1-(3′,4′-dihydroxyphenyl)-3-(2″,4″,6″-trihydroxyphenyl)propan-2-ol, activity exhibited by only a few human intestinal bacteria.

Cranberry procyanidins have been associated with an effect against urinary tract infections (UTI) for decades, and
European health claims are requested. This study compares the procyanidin profiles and concentrations of American cranberry (Vaccinium macrocarpon Ait.), European cranberry (Vaccinium oxycoccus L.), and lingonberry (Vaccinium vitis-idaea L.) analyzed using ultrahigh-performance liquid chromatoraphy coupled to a triple-quadrupole mass spectrometer with electrospray interface
(UHPLC-MS2). Concentrations of A-type trimers, procyanidin A2, catechin, epicatechin, and B-type dimers and trimers have been evaluated and compared for the first time in the three berries. The data clearly show remarkable differences in the procyanidin profiles and concentrations, especially the lack of A-type trimers in V. oxycoccus; thus, the effectiveness against UTI may vary among the Vaccinium species. These differences can be used to prove authenticity.

The human health benefits from consumption of cranberry products have been associated with the fruits’ unique flavonoid composition, including a complex profile of anthocyanins and proanthocyanidins. However, when
processed by techniques such as pressing, canning, concentrating, or drying, a number of these natural components may be compromised or inactivated due to physical separation, thermal degradation, or oxidation. Fresh cranberries were compared to freeze-dried berries and individual fruit tissues (skin and peeled fruit). Products examined included cranberry juices (commercial and prepared from concentrate), cranberry sauces (commercial and homemade), and sweetened-dried cranberries (commercial). Freeze-drying resulted in no detectable losses of anthocyanins or proanthocyanidins from cranberry
fruits. Anthocyanins were localized in the skin. Proanthocyanins were higher in the skin than in the flesh, with the exception of procyanidin A-2 dimer which was concentrated in the flesh. Anthocyanins were significantly higher in not-from-concentrate juice than in reconstituted juice from concentrate (8.3 mg and 4.2 mg/100 mL, respectively). Similarly, proanthocyanidins were markedly higher in not-from-concentrate juice compared to juice from concentrate (23.0 mg and 8.9 mg/100 mL, respectively). Homemade sauce contained far higher anthocyanins and proanthocyanidins (15.9 and 87.9 mg/100 g, respectively) than canned sauces processed with whole berries (9.6 and 54.4 mg/100 g, respectively) or jelled-type (1.1 and 16 mg/100 g, respectively). Sweetened-dried cranberries were quite low in anthocyanins
(7.9 mg/100 g), but they still retained considerable proanthocyanidins (64.2 mg/100 g). Commercially processed products contained significantly lower levels of polyphenols as compared to fresh and home-processed preparations. Anthocyanins were more sensitive to degradation than proanthocyanidins.

Purpose: Proanthocyanidins found in cranberry have been reported to have in vitro and in vivo antibacterial activity. We determined the effectiveness of cranberry juice for the prevention of urinary tract infections in children.
Materials and Methods: A total of 40 children were randomized to receive daily cranberry juice with high concentrations of proanthocyanidin vs cranberry
juice with no proanthocyanidin for a 1-year period. The study was powered to detect a 30% decrease in the rate of symptomatic urinary tract infection with type I and II errors of 0.05 and 0.2, respectively. Toilet trained children up to age 18 years were eligible if they had at least 2 culture
documented nonfebrile urinary tract infections in the calendar year before enrollment. Patients with anatomical abnormalities (except for primary vesicoureteral
reflux) were excluded from study. Subjects were followed for 12 months. The participants, clinicians, outcome assessor and statistician were all blinded to treatment allocation.
Results: Of the children 39 girls and 1 boy were recruited. Mean and median patient age was 9.5 and 7 years, respectively (range 5 to 18). There were 20 patients with comparable baseline characteristics randomized to each group. After 12 months of followup the average incidence of urinary tract infection in the treatment group was 0.4 per patient per year and 1.15 in the placebo group
(p 0.045), representing a 65% reduction in the risk of urinary tract infection.
Conclusions: Cranberry juice with high concentrations of proanthocyanidin appears to be effective in the prevention of pediatric nonfebrile urinary tract infections. Further studies are required to determine the cost-effectiveness of this approach.