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In Vitro Activity of Vaccinium Macrocarpon (cranberry) on Urinary Tract Pathogens in Uncomplicated Urinary Tract Infection.

Posted: March 23, 2016
Authors: Bukhari S, Chiragh S, Tariq S, Alam MA, Wazir MS, Suleman M.
Journal: J Ayub Med Coll Abbottabad 27(3):660-3.

Abstract: Background: Urinary tract infection is the most common bacterial infection in the community, mainly caused by Escherichia coli (E. coli). Due to its high incidence and recurrence, problems are faced in the treatment with antibiotics. Cranberry being herbal remedy have long been the focus of interest for their beneficial effects in preventing urinary tract infections. This study was conducted to analyse in vitro activity of cranberry (Vaccinium macrocarpon) on uropathogenic E. coli in uncomplicated urinary tract infections. Methods: In this laboratory based single group experimental study, anti-bacterial activity of Vaccinium macrocarpon concentrate on urinary tract E. coli was investigated, in vitro. Ninety-six culture positive cases of different uropathogens were identified. Vaccinium macrocarpon concentrate at different concentrations was prepared in distilled water and put in wells punched in nutrient agar. E. coli isolates were inoculated on the plates and incubated at 37 oC for 24 hours. A citric acid solution of the same pH as that of Vaccinium macrocarpon was used and put in a well on the same plate to exclude the effect of pH. Results: A total of 35 isolates of E. coli were identified out of 96 culture positive specimens of urine and found sensitive to Vaccinium macrocarpon (p<0.000). Results revealed that Vaccinium macrocarpon has antibacterial effect against E. coli. Furthermore the antibacterial activity of Vaccinium macrocarpon has dose response relationship. Acidic nature of Vaccinium macrocarpon due to its pH is not contributory towards its antibacterial effect. Conclusion: Vaccinium macrocarpon concentrate may be used in urinary tract infection caused by E. coli.

Anti-Adhesive Activity of Cranberry Phenolic Compounds and Their Microbial-Derived Metabolites against Uropathogenic Escherichia coli in Bladder Epithelial Cell Cultures

Posted: September 28, 2015
Authors: de Llano DG, Esteban-Fernandez A, Sanchez-Patan F, Martinlvarez PJ, Moreno-Arribas MV, Bartolome B
Journal: Int J Mol Sci 16(6):12119-30

Abstract: Cranberry consumption has shown prophylactic effects against urinary tract infections (UTI), although the mechanisms involved are not completely understood. In this paper, cranberry phenolic compounds and their potential microbial-derived metabolites (such as simple phenols and benzoic, phenylacetic and phenylpropionic acids) were tested for their capacity to inhibit the adherence of uropathogenic Escherichia coli (UPEC) ATCC53503TM to T24 epithelial bladder cells. Catechol, benzoic acid, vanillic acid, phenylacetic acid and 3,4-dihydroxyphenylacetic acid showed anti-adhesive activity against UPEC in a concentration-dependent manner from 100-500 micro M, whereas procyanidin A2, widely reported as an inhibitor of UPEC adherence on uroepithelium, was only statistically significant (p < 0.05) at 500 micro M (51.3% inhibition). The results proved for the first time the anti-adhesive activity of some cranberry-derived phenolic metabolites against UPEC in vitro, suggesting that their presence in the urine could reduce bacterial colonization and progression of UTI.

Cranberry Xyloglucan Structure and Inhibition of Escherichia coli Adhesion to Epithelial Cells.

Posted: September 28, 2015
Authors: Hotchkiss AT Jr, Nunez A, Strahan GD, Chau HK, White AK, Marais JP, Hom K, Vakkalanka MS, Di R, Yam KL, Khoo C
Journal: J Agric Food Sci 63(23):5622-33

Abstract: Cranberry juice has been recognized as a treatment for urinary tract infections on the basis of scientific reports of proanthocyanidin anti-adhesion activity against Escherichia coli as well as from folklore. Xyloglucan oligosaccharides were detected in cranberry juice and the residue remaining following commercial juice extraction that included pectinase maceration of the pulp. A novel xyloglucan was detected through tandem mass spectrometry analysis of an ion at m/z 1055 that was determined to be a branched, three hexose, four pentose oligosaccharide consistent with an arabino-xyloglucan structure. Two-dimensional nuclear magnetic resonance spectroscopy analysis provided through-bond correlations for the alpha-l-Araf (1->2) alpha-d-Xylp (1->6) beta-d-Glcp sequence, proving the S-type cranberry xyloglucan structure. Cranberry xyloglucan-rich fractions inhibited the adhesion of E. coli CFT073 and UTI89 strains to T24 human bladder epithelial cells and that of E. coli O157:H7 to HT29 human colonic epithelial cells. SSGG xyloglucan oligosaccharides represent a new cranberry bioactive component with E. coli anti-adhesion activity and high affinity for type 1 fimbriae.

Inhibition of Pseudomonas aeruginosa PAO1 adhesion to and invasion of A549 lung epithelial cells by natural extracts.

Posted: April 1, 2015
Authors: Ahmed GF, Elkhatib WF, Noreddin AM
Journal: J Infect Public Health 7(5):436-44.

Abstract: Pseudomonas aeruginosa colonizes the lungs in cystic fibrosis (CF) and mechanically ventilated patients by binding to the cellular receptors on the surface of the lung epithelium. Studies have shown that blocking this interaction could be achieved with sub-minimum inhibitory concentrations of antibiotics such as ciprofloxacin. The development of bacterial resistance is a probable drawback of such an intervention. The use of natural extracts to interfere with bacterial adhesion and invasion has recently gained substantial attention and is
hypothesized to inhibit bacterial binding and consequently prevent or reduce pathogenicity. This study used an A549 lung epithelial cell infection model, and the results revealed that a combination of aqueous cranberry extract with ciprofloxacin could completely prevent the adhesion and invasion of P. aeruginosa PAO1 compared to the untreated control. All of the natural extracts (cranberry, dextran, and soybean extracts) and ciprofloxacin showed a significant reduction (P<0.0001) in P. aeruginosa PAO1 adhesion to and invasion of lung epithelial
cells relative to the control. The cranberry, dextran, and soybean extracts could substantially increase the anti-adhesion and anti-invasion effects of ciprofloxacin to the averages of 100% (P<0.0001), 80% (P<0.0001), and 60%
(P<0.0001), respectively. Those extracts might result in a lower rate of the development of bacterial resistance; they are relatively safe and inexpensive agents, and utilizing such extracts, alone or in combination with ciprofloxacin,
as potential anti-adhesion and anti-invasion remedies, could be valuable in preventing or reducing P. aeruginosa lung infections.

Microbial catabolism of procyanidins by human gut microbiota.

Posted: April 1, 2015
Authors: Ou K, Sarnoski P, Schneider KR, Song K, Khoo C, Gu L
Journal: Mol Nutr Food Res 58(11):2196-205.

Abstract: SCOPE: A major portion of ingested procyanidins is degraded by human microbiota in the colon into various phenolic compounds. These microbial metabolites are thought to contribute to the health benefits of procyanidins in vivo. The
objective of this study was to identify and quantify the microbial metabolites of procyanidins after anaerobic fermentation with human microbiota.
METHODS AND RESULTS: (-)-Epicatechin, (+)-catechin, procyanidin B2, procyanidin A2, partially purified apple and cranberry procyanidins were incubated with human
microbiota at a concentration equivalent to 0.5 mM epicatechin. GC-MS analysis showed that common metabolites of all six substrates were benzoic acid, 2-phenylacetic acid, 3-phenylpropionic acid, 2-(3'-hydroxyphenyl)acetic acid,
2-(4'-hydroxyphenyl)acetic acid, 3-(3'-hydroxyphenyl)propionic acid, and hydroxyphenylvaleric acid. 5-(3',4'-Dihydroxyphenyl)-&#947;-valerolactones and 5-(3'-hydroxyphenyl)-&#947;-valerolactones were identified as the microbial metabolites of epicatechin, catechin, procyanidin B2, and apple procyanidins but not from the procyanidin A2 or cranberry procyanidin ferments. 2-(3',4'-Dihydroxyphenyl)acetic acid was only found in the fermented broth of procyanidin B2, A2, apple, and cranberry procyanidins. The mass recoveries of microbial metabolites range from 20.0 to 56.9% for the six substrates after 24 h
of fermentation.
CONCLUSION: Procyanidins, both B-type and A-type can be degraded by human gut microbiota. The microbial metabolites may contribute to the bioactivities of procyanidins.

Non-toxic plant metabolites regulate Staphylococcus viability and biofilm formation: a natural therapeutic strategy useful in the treatment and prevention of skin infections.

Posted: April 1, 2015
Authors: Morán A, Gutiérrez S, Martínez-Blanco H, Ferrero MA, Monteagudo-Mera A, Rodríguez-Aparicio LB.
Journal: Biofouling 30(10):1175-82.

Abstract: In the present study, the efficacy of generally recognised as safe (GRAS) antimicrobial plant metabolites in regulating the growth of Staphylococcus aureus and S. epidermidis was investigated. Thymol, carvacrol and eugenol showed the
strongest antibacterial action against these microorganisms, at a subinhibitory concentration (SIC) of &#8804; 50 &#956;g ml(-1). Genistein, hydroquinone and resveratrol showed antimicrobial effects but with a wide concentration range (SIC = 50-1,000 &#956;g ml(-1)), while catechin, gallic acid, protocatechuic acid, p-hydroxybenzoic acid and cranberry extract were the most biologically compatible molecules (SIC &#8805; 1000 &#956;g ml(-1)). Genistein, protocatechuic acid, cranberry extract, p-hydroxybenzoic acid and resveratrol also showed anti-biofilm activity against S. aureus, but not against S. epidermidis in which, surprisingly, these metabolites stimulated biofilm formation (between 35% and 1,200%). Binary combinations of cranberry extract and resveratrol with genistein, protocatechuic or p-hydroxibenzoic acid enhanced the stimulatory effect on S. epidermidis biofilm formation and maintained or even increased S. aureus anti-biofilm

Anti-adhesion activity of A2-type proanthocyanidins (a cranberry major component) on uropathogenic E. coli and P. mirabilis strains.

Posted: July 25, 2014
Authors: Nicolosi D, Tempera G, Genovese C, Furneri PM
Journal: Antibiotics 3(2):143-54

Abstract: Urinary tract infections (UTIs) are relatively common in women and may be classified as uncomplicated or complicated, depending upon the urinary tract anatomy and physiology. Acute uncomplicated cystitis (AUC) occurs when urinary pathogens from the bowel or vagina colonize the periurethral mucosa and reach the bladder. The vast majority of episodes in healthy women involving the same bacterial strain that caused the initial infection are thought to be reinfections. About 90% of AUC are caused by uropathogenic Escherichia coli (UPEC), but Proteus mirabilis also plays an important role. Several studies support the importance of cranberry (Vaccinium macrocarpon) proanthocyanidins in preventing adhesion of P-fimbriated UPEC to uroepithelial cells. In this study, we evaluated the in vitro anti-adhesion activity of A2-linked proanthocyanidins from cranberry on a UPEC and Proteus mirabilis strains and their possible influence on urease activity of the latter. A significant reduction of UPEC adhesion (up to 75%) on the HT1376 cell line was observed vs. control. For the strains of P. mirabilis there was also a reduction of adhesion (up to 75%) compared to controls, as well as a reduction in motility and urease activity. These results suggest that A2-type cranberry proanthocyanidins could aid in maintaining urinary tract health.

Cranberry-derived proanthocyanidins prevent formation of Candida albicans biofilms in artificial urine through biofilm- and adherence-specific mechanisms.

Posted: July 25, 2014
Authors: Rane HS, Bernardo SM, Howell AB, Lee SA
Journal: J Antimicrob Chemother 69(2):428-36

Abstract: OBJECTIVES: Candida albicans is a common cause of nosocomial urinary tract infections (UTIs) and is responsible for increased morbidity and healthcare costs. Moreover, the US Centers for Medicare & Medicaid Services no longer reimburse for hospital-acquired catheter-associated UTIs. Thus, development of specific approaches for the prevention of Candida urinary infections is needed. Cranberry juice-derived proanthocyanidins (PACs) have efficacy in the prevention of bacterial UTIs, partially due to anti-adherence properties, but there are limited data on their use for the prevention and/or treatment of Candida UTIs. Therefore, we sought to systematically assess the in vitro effect of cranberry-derived PACs on C. albicans biofilm formation in artificial urine.

METHODS: C. albicans biofilms in artificial urine were coincubated with cranberry PACs at serially increasing concentrations and biofilm metabolic activity was assessed using the XTT assay in static microplate and silicone disc models.

RESULTS: Cranberry PAC concentrations of >16 mg/L significantly reduced biofilm formation in all C. albicans strains tested, with a paradoxical effect observed at high concentrations in two clinical isolates. Further, cranberry PACs were additive in combination with traditional antifungals. Cranberry PACs reduced C. albicans adherence to both polystyrene and silicone. Supplementation of the medium with iron reduced the efficacy of cranberry PACs against biofilms.

CONCLUSIONS: These findings indicate that cranberry PACs have excellent in vitro activity against C. albicans biofilm formation in artificial urine. We present preliminary evidence that cranberry PAC activity against C. albicans biofilm formation is due to anti-adherence properties and/or iron chelation.

Evaluating the binding of selected biomolecules to cranberry derived proanthocyanidins using the quartz crystal microbalance.

Posted: July 25, 2014
Authors: Weckman NE, Olsson AL, Tufenkji N
Journal: Biomacromolecules 15(4):1375-81

Abstract: Despite cranberry being associated with the prevention of bacterial infections for over a century, our understanding of the bioavailability and mechanisms by which cranberry prevents infection is limited. This study investigates the interactions between cranberry proanthocyanidins (CPAC) and human serum proteins (albumin, alpha-1-acid glycoprotein, and fibrinogen) that may be encountered during CPAC metabolism following ingestion. To better understand how CPAC might interfere with bacterial infection, we also examined the interactions between CPAC and selected bacterial virulence factors; namely, lipopolysaccharide (LPS) and rhamnolipid. The binding of CPAC to the serum proteins, rhamnolipids and LPS from Escherichia coli O111:B4 can be described by Langmuir-type isotherms, allowing the determination of the apparent adsorption affinity constants, with CPAC interacting most strongly with fibrinogen with a binding constant of 2.2 x 10(8) M(-1). These binding interactions will limit the bioavailability of the CPAC at the site of action, an important consideration in designing further clinical trials. Furthermore, CPAC interacts with Pseudomonas aeruginosa 10 LPS, E. coli O111:B4 LPS, and P. aeruginosa rhamnolipids in fundamentally different manners, supporting the theory that cranberry prevents bacterial infections via multiple mechanisms.

Ratio of "A-type" to "B-type" proanthocyanidin interflavan bonds affects extra-intestinal pathogenic Escherichia coli invasion of gut epithelial cells.

Posted: July 25, 2014
Authors: Feliciano RP, Meudt JJ, Shanmuganayagam D, Krueger CG, Reed JD
Journal: J Agric Food Chem 62(18):3919-25

Abstract: Gut colonization by extra-intestinal pathogenic Escherichia coli (ExPEC) increases the risk of subsequent infections, including urinary tract infection and septicemia. Previous work suggests that cranberry proanthocyanidins (PAC) interact with bacterial surface factors, altering bacterial interaction with host cells. Methods were developed to determine if ratios of "A-type" to "B-type" interflavan bonds in PAC affect ExPEC agglutination and invasion of enterocytes. In cranberries, 94.5% of PAC contain one or more "A-type" bonds, whereas in apples, 88.3% of PAC contain exclusively "B-type" bonds. Results show that cranberry "A-type" PAC have greater bioactivity than apple "B-type" PAC for increasing ExPEC agglutination and decreasing ExPEC epithelial cell invasion.

Cranberry impairs selected behaviors essential for virulence in Proteus mirabilis HI4320

Posted: September 15, 2013
Authors: McCall J, Hidalgo G, Asadishad B, Tufenkji N
Journal: Can J Microbiol 59(6):430-436

Abstract: Proteus mirabilis is an etiological agent of complicated urinary tract infections. North American cranberries (Vaccinium macrocarpon) have long been considered to have protective properties against urinary tract infections. This work reports the effects of cranberry powder (CP) on the motility of P. mirabilis HI4320 and its expression of flaA, flhD, and ureD. Our results show that swimming and swarming motilities and swarmer-cell differentiation were inhibited by CP. Additionally, transcription of the flagellin gene flaA and of flhD, the first gene of the flagellar master operon flhDC, decreased during exposure of P. mirabilis to various concentrations of CP. Moreover, using ureD-gfp, a fusion of the urease accessory gene ureD with gfp, we show that CP inhibits urease expression. Because we demonstrate that CP does not inhibit the growth of P. mirabilis, the observed effects are not attributable to toxicity. Taken together, our results demonstrate that CP hinders motility of P. mirabilis and reduces the expression of important virulence factors.

Inhibition of bacterial motility and spreading via release of cranberry derived materials from silicone substrates

Posted: September 15, 2013
Authors: Chan M, Hidalgo G, Asadishad B, Almeida S, Muja N, Mohammadi MS, Nazhat SN, Tufenkji N
Journal: Colloid Surface B 110:275-80

Abstract: The motility of bacteria plays a key role in their colonization of surfaces during infection. Derivatives of cranberry fruit have been shown to interfere with bacterial motility. Herein, we report on the incorporation of cranberry derived materials (CDMs) into silicone substrates with the aim of impairing bacterial pathogen motility and spreading on the substrate surface. The release of CDMs from the silicone substrates when soaking in an aqueous medium was quantified for a period of 24h. Next, we showed that CDMs released from two silicone substrates remain bioactive as they downregulate the expression of the flagellin gene of two key uropathogens - Escherichia coli CFT073 and Proteus mirabilis HI4320. Furthermore, we demonstrate that CDM-modified silicone inhibits the swarming motility of P. mirabilis, an aggressive swarmer. The bioactive, CDM-modified substrates can find broad applications in the medical device and food industries where the impairment of bacterial colonization of surfaces is of paramount importance.

The effect of American cranberry (Vaccinium macrocarpon) constituents on the growth inhibition, membrane integrity, and injury of Escherichia coli O157:H7 and Listeria monocytogenes in comparison to Lactobacillus rhamnosus.

Posted: September 15, 2013
Authors: Lacombe A, McGivney C, Tadepalli S, Sun XiaoHong Wu VCH
Journal: Food Microbiol 34(2):352-359

Abstract: 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.

The specific degree-of-polymerization of A-type proanthocyanidin oligomers impacts Streptococcus mutans glucan-mediated adhesion and transcriptome responses within biofilms

Posted: September 15, 2013
Authors: Feng G, Klein MI, Gregoire S, Singh AP, Vorsa N, Koo H
Journal: Biofouling 29(6):629-40

Abstract: 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.

Capability of Lactobacillus plantarum IFPL935 To Catabolize Flavan-3-ol Compounds and Complex Phenolic Extracts

Posted: October 30, 2012
Authors: Sanchez-Patan F, Tabasco R, Monagas M, Requena T, Pelaez C, Moreno-Arribas MV, Bartolome B
Journal: J Agric Food Chem 60(29):7142-51

Abstract: 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 (&#8722;)-epicatechin-3-O-gallate and B-type dimeric procyanidins. Despite these findings, the strain was capable of rapidly degrading (&#8722;)-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&#8242;,4&#8242;-dihydroxyphenyl)-3-(2&#8243;,4&#8243;,6&#8243;-trihydroxyphenyl)propan-2-ol, activity exhibited by only a few human intestinal bacteria.

Effects of a Variety of Food Extracts and Juices on the Specific Binding Ability of Norovirus GII.4 P Particles

Posted: October 30, 2012
Authors: Li D, Baert L, Xia M, Zhong W, Jiang X, Uyttendaele M
Journal: J Food Prot 75(7): 1350-4

Abstract: The effects of 13 food extracts and juices, including shellfish, fruits, and vegetables, on the binding ability of human norovirus (NoV) were examined, using P particles of human NoV GII.4 as a research surrogate. The enhancements (positive values) or reductions (negative values) of NoV P particle detection (changes in optical density at 450 nm) in the presence of different
food extracts and juices as compared with P particles diluted in phosphate-buffered saline were tested by saliva-binding, enzymelinked immunosorbent assay in triplicate. In the presence of different food extracts and juices at different concentrations, an increase or decrease of the receptor-binding ability of the NoV P particles was observed. Due to a higher specific binding and thus a higher
accumulation of the viral particles, oysters may be contaminated with human NoV more often than other shellfish species (mussel, hard clams, and razor clams). Cranberry and pomegranate juices were shown to reduce the specific binding ability of human NoV P particles. No such binding inhibition effects were observed for the other tested extracts of fresh produce (strawberry, blackberry,
blueberry, cherry tomato, spinach, romaine lettuce) or, notably, for raspberry, which has been associated with human NoV outbreaks.

Tannin derived materials can block swarming motility and enhance biofilm formation in Pseudomonas aeruginosa

Posted: October 30, 2012
Authors: O'May C, Ciobanu A, Lam H, Tufenkiji N
Journal: Biofouling 28(10):1063-76

Abstract: Surface-associated swarming motility is implicated in enhanced bacterial spreading and virulence, hence it follows
that anti-swarming effectors could have clinical benefits. When investigating potential applications of anti-swarming
materials it is important to consider whether the lack of swarming corresponds with an enhanced sessile biofilm
lifestyle and resistance to antibiotics. In this study, well-defined tannins present in multiple plant materials (tannic
acid (TA) and epigallocathecin gallate (EGCG)) and undefined cranberry powder (CP) were found to block swarming motility and enhance biofilm formation and resistance to tobramycin in Pseudomonas aeruginosa. In contrast, gallic acid (GA) did not completely block swarming motility and did not affect biofilm formation or tobramycin resistance. These data support the theory that nutritional conditions can elicit an inverse relationship between swarming motility and biofilm formation capacities. Although anti-swarmers exhibit the potential to yield clinical benefits, it is important to be aware of possible implications regarding biofilm formation and antibiotic resistance.

Antibacterial effects of plant-derived extracts on methicillin-resistant Staphylococcus aureus.

Posted: July 31, 2012
Authors: Su XW, Howell AB, D'Souza DH
Journal: Foodborne Pathog Dis 9(6):573-8

Abstract: Natural chemicals have been reported to have antibacterial effects against a variety of bacteria. The present study evaluated the antibacterial effects of commercially available grape-seed extract (GSE), pomegranate polyphenols (PP), and lab-prepared cranberry proanthocyanidins (C-PAC) against two strains of methicillin-resistant Staphylococcus aureus (MRSA). GSE, PP, and C-PAC at concentrations of 2 mg/mL, 10 mg/mL, or controls were mixed with equal volumes of overnight cultures of MRSA at ~6 log10 colony-forming units (CFU)/mL and incubated for 0, 1, 2, 8, and 24 h at 37 degrees C. Treatments were neutralized/stopped using tryptic soy broth containing 3% beef extract. Serial dilutions of the treated MRSA strains and controls were spread-plated on trypticase soy agar and incubated for 24-48 h at 37 degrees C and colonies were counted. Among the three tested agents, GSE at 1 and 5 mg/mL was found to be most effective against MRSA, resulting in a 2.9-4.0 log10 CFU/mL reduction of both strains after 2 h at 37 degrees C. PP at 1 and 5 mg/mL was found to cause 1.1-2.3 log10 CFU/mL reduction, while C-PAC at 1 mg/mL caused <1 log10 CFU/mL reduction of the two MRSA strains after 2 h at 37 degrees C. All three extracts at the tested concentrations decreased the two MRSA strains to undetectable levels within 24 h, with the exception of 1 mg/mL PP for strain 33591. Scanning electron microscopy of MRSA after 2 h of treatment showed that GSE and PP caused bacterial cell wall alteration, with negligible effect observed by C-PAC treatment. However, the in vivo activity and clinical safety applications of GSE, PP, and C-PAC need to be evaluated before suggestion for use as a treatment/control measure.

Comparison of isolated cranberry (Vaccinium macrocarpon Ait.) proanthocyanidins to catechin and procyanidins A2 and B2 for use as standards in the 4-(dimethylamino)cinnamaldehyde assay

Posted: July 31, 2012
Authors: Feliciano RP, Shea MP, Shanmuganayagam D, Krueger CG, Howell AB, Reed JD
Journal: J Agric Food Chem 60(18):4578-85

Abstract: The 4-(dimethylamino)cinnamaldehyde (DMAC) assay is currently used to quantify proanthocyanidin (PAC) content in cranberry products. However, this method suffers from issues of accuracy and precision in the analysis and comparison of PAC levels across a broad range of cranberry products. Current use of procyanidin A2 as a standard leads to an underestimation of PACs content in certain cranberry products, especially those containing higher molecular weight PACs. To begin to address the issue of accuracy, a method for the production of a cranberry PAC standard, derived from an extraction of cranberry (c-PAC) press cake, was developed and evaluated. Use of the c-PAC standard to quantify PAC content in cranberry samples resulted in values that were 2.2 times higher than those determined by procyanidin A2. Increased accuracy is critical for estimating PAC content in relationship to research on authenticity, efficacy, and bioactivity, especially in designing clinical trials for determination of putative health benefits.

Cranberry proanthocyanidins act in synergy with licochalcone A to reduce Porphyromonas gingivalis growth and virulence properties, and to suppress cytokine secretion by macrophages

Posted: July 31, 2012
Authors: Feldman M, Grenier D
Journal: J Appl Microbiol 113(2):438-47

Abstract: "Aims:&#8194; Periodontitis is an inflammatory disease of polymicrobial origin that affects the tooth-supporting tissues. With the spread of antibiotic resistance among pathogenic bacteria, alternative strategies are required to better control infectious diseases such as periodontitis. The aim of our study was to investigate whether two natural compounds, A-type cranberry proanthocyanidins (AC-PACs) and licochalcone A, act in synergy against Porphyromonas gingivalis and the host inflammatory response of a macrophage model.

Methods and Results:&#8194; Using a checkerboard microtitre test, AC-PACs and licochalcone A were found to act in synergy to inhibit P. gingivalis growth and biofilm formation. Fluorescein isothiocyanate-labelled P. gingivalis adhesion to oral epithelial cells was also inhibited by a combination of the two natural compounds in a synergistic manner. Fluorometric assays showed that although AC-PACs and licochalcone A reduced both MMP-9 and P. gingivalis collagenase activities, no synergy was obtained with a combination of the compounds. Lastly, AC-PACs and licochalcone A also acted in synergy to reduce the lipopolysaccharide (LPS)-induced secretion of the pro-inflammatory mediators IL-1&#946;, TNF-&#945;, IL-6 and IL-8 in a macrophage model.

Conclusions:&#8194; A-type cranberry proanthocyanidins and licochalcone A, natural compounds from cranberry and licorice, respectively, act in synergy on both P. gingivalis and the host immune response, the two principal etiological factors of periodontitis.

Significance and Impact of the Study:&#8194; The combined use of AC-PACs and licochalcone A may be a potential novel therapeutic strategy for the treatment and prevention of periodontal disease."

Effects of Cranberry Extracts on Growth and Biofilm Production of Escherichia coli and Staphylococcus species

Posted: July 31, 2012
Authors: LaPlante KL, Sarkisian SA, Woodmansee S, Rowley DC, Seeram NP
Journal: Phytother Res doi: 10.1002/ptr.4592

Abstract: Biofilm producing bacteria such as Staphylococcus species and Escherichia coli are the most common cause of catheter related urinary tract infections (UTIs). The American cranberry (Vaccinium macrocarpon) is utilized widely as a prophylaxis for UTIs due to its prevention of microbial adhesion. Cranberry contains proanthocyanidins (PACs), which have been implicated as active constituents responsible for its bacterial antiadhesive properties. Despite overwhelming data supporting cranberry's beneficial effects against human pathogenic bacteria, there is limited information regarding its effects on biofilm formation. This study evaluated the effects of three proprietary PAC-standardized cranberry extracts on the inhibition of bacterial growth and biofilm production against a panel of clinically relevant pathogens: Staphylococcus epidermidis, Staphylococcus aureus, clinical methicillin-resistant S. aureus (MRSA), Staphylococcus saprophyticus and Escherichia coli. The extracts inhibited the growth of the Gram-positive bacteria (Staphylococcus spp.) but not the Gram-negative species (E. coli) with minimum inhibitory concentrations in the range 0.02–5&#8201;mg/mL. The extracts also inhibited biofilm production by the Gram-positive bacteria but did not eradicate their established biofilm. These results suggest that cranberry may have beneficial effects against the growth and biofilm producing capability of Gram-positive bacteria pathogens.

High molecular weight constituents of cranberry interfere with influenza virus neuraminidase activity

Posted: July 31, 2012
Authors: Oiknine-Djian E, Houri-Haddad Y, Weiss EI, Ofek I, Greenbaum E, Hartshorn K, Zakay-Rones Z
Journal: Planta Med 78(10):962-7

Abstract: Cranberry juice contains high molecular weight non-dialyzable material (NDM) which was found to inhibit hemagglutination induced by the influenza virus (IV) as well as to neutralize the cytotoxicity of IV in cell cultures. Because influenza virus surface glycoproteins hemagglutinin (HA) and neuraminidase (NA) are involved in viral replication and in the infectious process, we sought in the present study to examine the effect of NDM on neuraminidases which are the target of most anti-influenza drugs today. NDM inhibited the NA enzymatic activity of influenza A and B strains as well as that of Streptococcus pneumoniae. This finding is of importance considering the emergence of influenza isolates resistant to antiviral drugs, reaching 90 % in some places. The anti-NA activity of NDM, evaluated by the MUNANA method and expressed as the concentration required for 50 % inhibition (IC50), was most potent against N1 (IC50, 192 microg/mL), less active against BN and N2 (IC50, 509 microg/mL and 1128 microg/mL, respectively), and moderately active against Streptococcus pneumoniae NA (IC50, 594 microg/mL). The in vitro findings of the present study suggest that cranberry constituents may have a therapeutic potential against both A and B influenza virus infections and might also interfere with the development of secondary bacterial complications

Impact of cranberry juice on initial adhesion of the EPS producing bacterium Burkholderia cepacia

Posted: July 31, 2012
Authors: Yang X, Teng F, Zeng H, Liu Y
Journal: Biofouling 28(5):417-31

Abstract: The impact of cranberry juice was investigated with respect to the initial adhesion of three isogenic strains of the bacterium Burkholderia cepacia with different extracellular polymeric substance (EPS) producing capacities, viz. a wild-type cepacian EPS producer PC184 and its mutant strains PC184rml with reduced EPS production and PC184bceK with a deficiency in EPS production. Adhesion experiments conducted in a parallel-plate flow chamber demonstrated that, in the absence of cranberry juice, strain PC184 had a significantly higher adhesive capacity compared to the mutant strains. In the presence of cranberry juice, the adhesive capacity of the EPS-producing strain PC184 was largely reduced, while cranberry juice had little impact on the adhesion behavior of either mutant strain. Thermodynamic modeling supported the results from adhesion experiments. Surface force apparatus (SFA) and scanning electron microscope (SEM) studies demonstrated a strong association between cranberry juice components and bacterial EPS. It was concluded that cranberry juice components could impact bacterial initial adhesion by adhering to the EPS and impairing the adhesive capacity of the cells, which provides an insight into the development of novel treatment strategies to block the biofilm formation associated with bacterial infection.

Antimicrobial effects of fractions from cranberry products on the growth of seven

Posted: April 30, 2012
Authors: Caillet S, Côté J, Sylvain JF, Lacroix M
Journal: Food Control 23;419-428

Abstract: The antimicrobial effect of thirty HPLC fractions of different polarity obtained from two cranberry juices and three extracts (anthocyanins, water-soluble and apolar phenolic compounds) isolated from frozen cranberries and pomace was investigated against seven bacterial strains Enterococcus faecium resistant to vancomycin (ERV), Escherichia coli O157:H7 EDL 933, Escherichia coli ATCC 25922, Listeria monocytogenes HPB 2812, Pseudomonas aeruginosa ATCC 15442; Salmonella Typhimurium SL1344 and Staphylococcus aureus ATCC 29213) The minimum inhibitory concentration (MIC) and the maximal tolerated concentration (MTC) of each fraction were determined for each pathogen using a 96-well microtiter plate method. The results, reported in mg phenol/mL, indicated that all the bacterial strains, both Gram-positive and Gram-negative, were selectively inhibited by the cranberry phenolic compounds. All pathogens were very sensitive to at least seven fractions with MTCs below 2 mg phenol/mL and five fractions with MICs below 10 mg phenol/mL. In addition, four fractions rich in apolar phenolic compounds were very efficient against all bacteria with MICs below 10 mg phenol/mL, and twenty five fractions completely inhibited microbial growth with MICs below100 mg phenol/well. L. monocytogenes exhibited the highest sensitivity with twelve very active fractions (MTCs and MICs below 1 and
10 mg phenol/mL, respectively) while E. coli O157H7 was the least sensitive to twenty seven fractions (with the highest MICs). Also, it appears that the technological process to manufacture cranberry juice can reduce the antimicrobial activity of phenolic fractions.

Comprehensive assessment of the quality of commercial cranberry products. Phenolic characterization and in vitro bioactivity

Posted: April 30, 2012
Authors: Sánchez-Patán F, Bartolomé B, Martín-Alvarez PJ, Anderson M, Howell A, Monagas M
Journal: J Agric Food Chem 60(13):3396-408

Abstract: Cranberry ( Vaccinium macrocarpon ) products have been widely recommended in traditional American medicine for the treatment of urinary tract infection (UTI). A total of 19 different commercial cranberry products from American and European markets have been analyzed by different global phenolic methods and by UPLC-DAD-ESI-TQ MS. In addition, in vitro antioxidant capacity and uropathogenic bacterial antiadhesion activity tests have been performed. Results revealed that products found in the market widely differed in their phenolic content and distribution, including products completely devoid of flavan-3-ols to highly purified ones, either in A-type proanthocyanidins (PACs) or in anthocyanins. The product presentation form and polyphenolic profile widely affected the antiadhesion activity, ranging from a negative (nulel) effect to a MIC = 0.5 mg/mL for cranberry powders and a MIC=112 mg/mL for gel capsule samples. Only 4 of 19 products would provide the recommended dose of intake of 36 mg total PACs/day. Of most importance was the fact that this dose would actually provide as low as 0.00 and up to 205 &#956;g/g of procyanidin A2, indicating the lack of product standardization and incongruence between global and individual compound analysis.

Cranberry proanthocyanidins inhibit the adherence properties of Candida albicans

Posted: April 30, 2012
Authors: Feldman M, Tanabe S, Howell A, Grenier D
Journal: BMC Complement Altern Med 16;12(1):6

Abstract: ABSTRACT: BACKGROUND: Oral candidiasis is a common fungal disease mainly caused by Candida albicans. The aim of this study was to investigate the effects of A-type cranberry proanthocyanidins (AC-PACs) on pathogenic properties of C. albicans as well as on the inflammatory response of oral epithelial cells induced by this oral pathogen. METHODS: Microplate dilution assays were performed to determine the effect of AC-PACs on C. albicans growth as well as biofilm formation stained with crystal violet. Adhesion of FITC-labeled C. albicans to oral epithelial cells and to acrylic resin disks was monitored by fluorometry. The effects of AC-PACs on C. albicans-induced cytokine secretion, nuclear factor-kappa B (NF-kappaB) p65 activation and kinase phosphorylation in oral
epithelial cells were determined by immunological assays. RESULTS: Although AC-PACs did not affect growth of C. albicans, it prevented biofilm formation and reduced adherence of C. albicans to oral epithelial cells and saliva-coated acrylic resin discs. In addition, AC-PACs significantly decreased the secretion of IL-8 and IL-6 by oral epithelial cells stimulated with C. albicans. This
anti-inflammatory effect was associated with reduced activation of NF-kappaB p65 and phosphorylation of specific signal intracellular kinases. CONCLUSION: AC-PACs by affecting the adherence properties of C. albicans and attenuating the inflammatory response induced by this pathogen represent potential novel therapeutic agents for the prevention/treatment of oral candidiasis.

Inhibition of adherence of multi-drug resistant E. coli by proanthocyanidin

Posted: April 30, 2012
Authors: Gupta A, Dwivedi M, Mahdi AA, Nagana Gowda GA, Khetrapal CL, Bhandari M
Journal: Urol Res 40(2):143-50

Abstract: Proanthocyanidin is commonly used for inhibiting urinary tract infection (UTI) of sensitive strains of Escherichia coli. The aim of this study was to investigate the effect of proanthocyanidin on adherence of uropathogenic multi-drug resistant E. coli to uroepithelial cells, which has not yet been investigated so far. Extracts of the purified proanthocyanidin were prepared from dried cranberry juice. Purity and structural assignment of proanthocyanidin was assessed using high performance liquid chromatography and (13)C nuclear magnetic resonance spectroscopy, respectively. Subsequently, its affect on multi-drug resistant bacteria as well as quantification of anti-adherence bioactivity on human vaginal and bladder epithelial cells was appraised. Inhibition of adherence to an extent of about 70% with multi-drug resistant E. coli strains was observed on uroepithelial cell. The anti-adherence bioactivity of the proanthocyanidin was detected at concentrations of 10-50 µg/ml with significant bacteriuria. Probable proanthocyanidin through A-type linkages either combines to P-fimbriae of bacterial cells or modifies the structural entity of P-fimbriae and inhibits bacterial adherence to uroepithelial cells. The proanthocyanidin exhibited anti-adherence property with multi-drug resistant strains of uropathogenic P-fimbriated E. coli with in vitro study. Hence proanthocyanidin may be considered as an inhibitory agent for multi-drug resistant strains of E. coli adherence to uroepithelial cells.

Inhibition of Streptococcus gordonii metabolic activity in biofilm by cranberry juice high-molecular-weight component

Posted: April 30, 2012
Authors: Babu J, Blair C, Jacob S, Itzhak O.
Journal: J Biomed Biotechnol 2012:590384

Abstract: Previous studies demonstrated that a cranberry high-molecular-mass, nondialyzable material (NDM) can inhibit adhesion of numerous species of bacteria and prevents bacterial coaggregation of bacterial pairs. Bacterial coaggregation leads to plaque formation leading to biofilm development on surfaces of oral cavity. In the present study, we evaluated the effect of low concentrations of NDM on Streptococcus gordonii metabolic activity and biofilm formation on restorative dental surfaces. We found that the NDM selectively inhibited metabolic activity of S. gordonii, without affecting bacterial viability. Inhibiting the metabolic activity of bacteria in biofilm may benefit the health of the oral cavity.

Study on the influence of cranberry extract &#379;uravit S·O·S(®) on the properties of uropathogenic Escherichia coli strains, their ability to form biofilm and its antioxidant properties.

Posted: April 30, 2012
Authors: Wojnicz D, Sycz Z, Walkowski S, Gabrielska J, Aleksandra W, Alicja K, Anna S&#321;, Hendrich AB
Journal: Phytomedicine 19(6):506-14

Abstract: Consumption of cranberries is known to exert positive health effects, especially against urinary tract infections. For this reason, presumably, they are widely used in folk medicine. Different aspects of cranberry phenolics activity were studied in individual papers but complex study in this matter is missing. The aim of the present study is to provide complex data concerning various aspects of cranberry extract activity. We studied the effects of subinhibitory concentrations of commercially available extract (&#379;uravit S·O·S(®)) against two Escherichia coli strains isolated from urine of patients with pyelonephritis. Additionally the main extract anthocyanins were characterized. The activity of extract against lipid peroxidation and its radical scavenging ability were also assessed. &#379;uravit S·O·S(®) decreased the hydrophobicity of one of the studied E. coli strains, reduced swimming motility and adhesion to epithelial cells of both studied strains, it also limited the ability of bacteria to form biofilm. Expression of curli was not affected by cranberry extract, the assessment of P fimbriae expression was not reliable due to extract-induced agglutination of erythrocytes. Cranberry extract caused filamentation in both studied E. coli strains. It also showed pronounced antioxidant and radical scavenging properties. The properties of the studied cranberry extract show that it could be effectively used in prevention and/or elimination of urinary tract infections, specially the recurrent ones.

The antimicrobial effects of cranberry against Staphylococcus aureus

Posted: April 30, 2012
Authors: Lian PY, Maseko T, Rhee M, Ng K.
Journal: Food Sci Technol Int 18(2):179-86

Abstract: The antimicrobial effects of the American cranberry (Vaccinium macrocarpon) on a major food-borne pathogen, Staphylococcus aureus, were investigated using commercially obtained Lakewood® organic cranberry juice and Ocean Spray® cranberry juice cocktail and four other berry fruit extracts (acai berry, strawberry, raspberry, and blueberry). The results showed that cranberry is a potent antimicrobial against S. aureus and the most potent among the berries studied. The order of percentage inhibition of bacterial growth at the same concentration of phenolic materials as gallic acid equivalents was Lakewood cranberry juice&#8201;>&#8201;Ocean Spray cranberry juice&#8201;&#8811;&#8201;blueberry&#8201;>&#8201;acai berry&#8201;&#8811;&#8201;raspberry&#8201;&#8811;&#8201;strawberry. The antimicrobial effect was not due to the acidity of the berries as NaOH-neutralized samples were almost as effective in terms of percentage inhibition of viable cell growth. Solid-phase extraction of cranberry juice using C18 solid phase showed that the antimicrobial effects reside exclusively with the C18-bound materials.

Inhibition of Adhesion of Uropathogenic Escherichia coli Bacteria to Uroepithelial Cells by Extracts from Cranberry

Posted: January 26, 2012
Authors: Ermel G, Georgeault S, Inisan C, Besnard M
Journal: J Med Food 15(2):126-34

Abstract: ABSTRACT Cranberry extract has been reported as a therapeutic agent, mainly in urinary tract infections due to its antiadhesive capacity. In order to compare the effects of proanthocyanidin (procyanidin) (PAC)-standardized cranberry extracts and commercial PAC A2, we first investigated the presence of genes encoding known adhesins on 13 strains of uropathogenic strains coming from patients with cystisis. After this characterization, the anti-adhesive effects of PAC A2 were assayed on selected uropathogenic Escherichia coli strains before testing cranberry extracts. Before checking inhibitory effect on bacterial adhesion to cells, we showed that neither PAC A2 or three cranberry extracts (A, B, and C) specifically inhibited the growth and did not supply any potential nutrient to E. coli strains, including the unrelated control strain. PAC A2 exhibited an inhibitory effect on the adhesion of two selected uropathogenic strains of E. coli. This work also showed that a preliminary exposure of bacteria to PAC A2 significantly reduced the adhesion. This phenomenon has been also observed with a lesser impact when uroepithelial cells were pretreated with PAC A2. Moreover, the assays were more robust when bacteria were in fast growing conditions (exponential phase): the adhesion to uroepithelial cells was greater. Significant reduction of adhesion to urepithelial cells was observed: around 80% of inhibition of adhesion with the cranberry extracts at equivalent PAC concentration of 50 µg/mL. The effects of the different assayed extracts were not obviously different except for extract B, which inhibited approximately 55% of adhesion at an equivalent PAC concentration of 5 µg/mL

Proanthocyanidin-rich Extracts from Cranberry Fruit ( Vaccinium macrocarpon Ait.) Selectively Inhibit the Growth of Human Pathogenic Fungi Candida spp. and Cryptococcus neoformans.

Posted: January 26, 2012
Authors: Patel KD. Scarano FJ. Kondo M. Hurta RA. Neto CC.
Journal: J Agric Food Chem 59(24):12864-73

Abstract: Cranberry ( Vaccinium macrocarpon ) has been shown in clinical studies to reduce infections caused by Escherichia coli and other bacteria, and proanthocyanidins are believed to play a role. The ability of cranberry to inhibit the growth of opportunistic human fungal pathogens that cause oral, skin, respiratory, and systemic infections has not been well-studied. Fractions from whole cranberry fruit were screened for inhibition of five Candida species and Cryptococcus neoformans , a causative agent of fungal meningitis. Candida glabrata , Candida lusitaniae , Candida krusei , and Cryptococcus neoformans showed significant susceptibility to treatment with cranberry proanthocyanidin fractions in a broth microdilution assay, with minimum inhibitory concentrations as low as 1 mug/mL. MALDI-TOF MS analysis of subfractions detected epicatechin oligomers of up to 12 degrees of polymerization. Those containing larger oligomers caused the strongest inhibition. This study suggests that cranberry has potential as an antifungal agent.

The effect of nondialyzable material (NDM) cranberry extract on formation of contact lens biofilm by Staphylococcus epidermidis

Posted: January 26, 2012
Authors: Leshem R, Maharshak I, Ben Jacob E, Ofek I, Kremer I
Journal: Invest Ophthalmol Vis Sci 52(7):4929-34

Abstract: PURPOSE: To assess the effects of NDM from cranberries on Staphylococcus epidermidis biofilm formed on soft contact lenses.

METHODS: Soft contact lenses were incubated in Tryptic Soy Broth (TSB) together with S. epidermidis (ATCC35984/RP62A) and various concentrations of NDM, and inspected by scanning electron and confocal microscopy. The TSB was collected after sonification and monitored turbidometrically.

RESULTS: NDM at >=500 mug/mL concentration caused a significant (P < 0.01) reduction of biofilm. Scanning electron microscopy of biofilm in the presence of 500 to 1000 mug/mL NDM confirmed these results. In control lenses, multilayered mushroom-shaped biofilm and complete coverage of the lens surface were seen, whereas after incubation with 500 mug NDM per mL TSB, the biofilm was thinner with smaller protuberances, and exposed lens surface was partially seen. In samples incubated with 1000 mug NDM per mL TSB, the lens surface was clearly seen between sporadic microcolonies.

CONCLUSIONS: NDM reduces formation of biofilm on soft contact lenses. This has important implications for the prevention of contact lens-related corneal infections caused by S. epidermidis.

The swarming motility of Pseudomonas aeruginosa is blocked by cranberry proanthocyanidins and other tannin-containing materials

Posted: January 26, 2012
Authors: O'May C, Tufenkji N
Journal: Appl Environ Microbiol 77(9):3061-7

Abstract: Bacterial motility plays a key role in the colonization of surfaces by bacteria and the subsequent formation of resistant communities of bacteria called biofilms. Derivatives of cranberry fruit, predominantly condensed tannins called proanthocyanidins (PACs) have been reported to interfere with bacterial adhesion, but the effects of PACs and other tannins on bacterial motilities remain largely unknown. In this study, we investigated whether cranberry PAC (CPAC) and the hydrolyzable tannin in pomegranate (PG; punicalagin) affected the levels of motilities exhibited by the bacterium Pseudomonas aeruginosa. This bacterium utilizes flagellum-mediated swimming motility to approach a surface, attaches, and then further spreads via the surface-associated motilities designated swarming and twitching, mediated by multiple flagella and type IV pili, respectively. Under the conditions tested, both CPAC and PG completely blocked swarming motility but did not block swimming or twitching motilities. Other cranberry-containing materials and extracts of green tea (also rich in tannins) were also able to block or impair swarming motility. Moreover, swarming bacteria were repelled by filter paper discs impregnated with many tannin-containing materials. Growth experiments demonstrated that the majority of these compounds did not impair bacterial growth. When CPAC- or PG-containing medium was supplemented with surfactant (rhamnolipid), swarming motility was partially restored, suggesting that the effective tannins are in part acting by a rhamnolipid-related mechanism. Further support for this theory was provided by demonstrating that the agar surrounding tannin-induced nonswarming bacteria was considerably less hydrophilic than the agar area surrounding swarming bacteria. This is the first study to show that natural compounds containing tannins are able to block P. aeruginosa swarming motility and that swarming bacteria are repelled by such compounds.

Effect of juice processing on cranberry antibacterial properties

Posted: January 22, 2012
Authors: Cote J, Caillet S, Dussault D, Sylvain JF, Lacroix M
Journal: Food Res Int 44: 9, 2922-2929

Abstract: The effects of the industrial juice process on the ability of neutralized cranberry samples and extracts (polar, apolar and anthocyanins) to inhibit the growth of Enterococcus faecium resistant to vancomycin (ERV), Escherichia coli O157:H7 EDL 933, E. coli ATCC 25922, Listeria monocytogenes HPB 2812, Pseudomonas aeruginosa ATCC 15442, Salmonella Typhimurium SL1344 and Staphylococcus aureus ATCC 29213 were investigated. The juice process appeared to have a general enhancing effect on the antibacterial properties of cranberry polar and anthocyanin extracts. The lowest minimum inhibitory concentrations (MICs) (1.80-7.0 micro g phenol/well) were obtained when S. aureus, S. Typhimurium, and ERV were exposed to the juice concentrate. The growth of P. aeruginosa, L. monocytogenes, E. coli ATCC, and E. coli O157:H7 was not inhibited by the juice concentrate, but did show sensitivity (maximal tolerated concentrations of 0.007-0.4 micro g phenol/well). The lowest MICs (22.6-90.5 micro g phenol/well) for P. aeruginosa, S. aureus, S. Typhimurium, and ERV were observed when they were exposed to the cranberry anthocyanin extract obtained from cranberry pomace. The results also showed a negative effect of the juice process on the antibacterial properties of the cranberry apolar extracts: the one obtained from frozen cranberries was most efficient against P. aeruginosa, S. aureus, L. monocytogenes and S. Typhimirium (MIC of 45.50 micro g phenol/well). The tested bacteria showed the greatest resistance toward the cranberry extracts obtained from the mash and the macerated and depectinized mash

Induction of a state of iron limitation in uropathogenic Escherichia coli CFT073 by cranberry-derived proanthocyanidins as revealed by microarray analysis

Posted: January 22, 2012
Authors: Hidalgo G, Ponton A, Fatisson J, O'May C, Asadishad B, Schinner T, Tufenkji N.
Journal: Appl Environ Microbiol 77(4):1532-5.

Abstract: Transcriptional profiles of uropathogenic Escherichia coli CFT073 exposed to cranberry-derived proanthocyanidins (PACs) were determined. Our results indicate that bacteria grown on media supplemented with PACs were iron deprived. To our knowledge, this is the first time that PACs have been shown to induce a state of iron limitation in this bacterium.

Inhibition of Escherichia coli CFT073 fliC expression and motility by cranberry materials.

Posted: January 22, 2012
Authors: Hidalgo G, Chan M, Tufenkji N
Journal: Appl Environ Microbiol 77(19):6852-7

Abstract: In humans, uropathogenic Escherichia coli (UPEC) is the most common etiological agent of uncomplicated urinary tract infections (UTIs). Cranberry extracts have been linked to the prevention of UTIs for over a century; however, a mechanistic understanding of the way in which cranberry derivatives prevent bacterial infection is still lacking. In this study, we used a fliC-lux reporter as well as quantitative reverse transcription-PCR to demonstrate that when UPEC strain CFT073 was grown or exposed to dehydrated, crushed cranberries or to purified cranberry-derived proanthocyanidins (cPACs), expression of the flagellin gene (fliC) was inhibited. In agreement with these results, transmission electron microscopy imaging of bacteria grown in the presence of cranberry materials revealed fewer flagella than those in bacteria grown under control conditions. Furthermore, we showed that swimming and swarming motilities were hindered when bacteria were grown in the presence of the cranberry compounds. Because flagellum-mediated motility has been suggested to enable UPEC to disseminate to the upper urinary tract, we propose that inhibition of flagellum-mediated motility might be a key mechanism by which cPACs prevent UTIs. This is the first report to show that cranberry compounds inhibit UPEC motility via downregulation of the fliC gene. Further studies are required to establish whether these inhibitors play a role in vivo.

Iron chelation by cranberry juice and its impact on Escherichia coli growth.

Posted: January 22, 2012
Authors: Lin B, Johnson BJ, Rubin RA, Malanoski AP, Ligler FS
Journal: Biofactors 37(2):121-30.

Abstract: The various health benefits of Vaccinium macrocarpon (cranberry) are well documented and have been attributed mainly to its antioxidant capacity and anti-adhesive activity. Several different mechanisms have been proposed to explain the possible role of cranberries, cranberry juice, and cranberry extracts in inhibiting bacterial growth. These mechanisms of action (i.e., inhibition of the microbial growth) have not been thoroughly studied. Here, we took advantage of current advances in microarray technology and used GeneChip® Escherichia coli genome 2.0 arrays to gain insight into the molecular mechanisms involved in the impact of cranberry juice on the properties of E. coli growth. The inclusion of cranberry juice in bacterial growth media was found to significantly impact the doubling time of E. coli. The gene expression results revealed altered expression of genes associated with iron transport and essential metabolic enzymes as well as with adenosine triphosphate (ATP) synthesis and fumarate hydratase in these cultures. The altered expression of genes associated with iron transport was consistent with the strong iron chelating capability of proanthocyanidins, a major constituent of cranberry juice. The iron depletion effect was confirmed by adding exogenous iron to the growth media. This addition partially reversed the inhibitory effect on bacterial growth observed in the presence of cranberry juice/extracts.

A-type cranberry proanthocyanidins inhibit the RANKL-dependent differentiation and function of human osteoclasts.

Posted: January 14, 2012
Authors: Tanabe S, Santos J, La VD, Howell AB, Grenier D
Journal: Molecules. 16(3):2365-74

Abstract: This study investigated the effect of A-type cranberry proanthocyanidins (AC-PACs) on osteoclast formation and bone resorption activity. The differentiation of human pre-osteoclastic cells was assessed by tartrate-resistant acid phosphatase (TRAP) staining, while the secretion of interleukin-8 (IL-8) and matrix metalloproteinases (MMPs) was measured by ELISA. Bone resorption activity was investigated by using a human bone plate coupled with an immunoassay that detected the release of collagen helical peptides. AC-PACs up to 100 microg/mL were atoxic for osteoclastic cells. TRAP staining evidenced a dose-dependent inhibition of osteoclastogenesis. More specifically, AC-PACs at 50 microg/mL caused a 95% inhibition of RANKL-dependent osteoclast differentiation. This concentration of AC-PACs also significantly increased the secretion of IL-8 (6-fold) and inhibited the secretion of both MMP-2 and MMP-9. Lastly, AC-PACs (10, 25, 50 and 100 microg/ml) affected bone degradation mediated by mature osteoclasts by significantly decreasing the release of collagen helical peptides. This study suggests that AC-PACs can interfere with osteoclastic cell maturation and physiology as well as prevent bone resorption. These compounds may be considered as therapeutic agents for the prevention and treatment of periodontitis.

Anti-Helicobacter activity of certain food plant extracts and juices and their composition in vitro

Posted: January 14, 2012
Authors: Babarikina A, Nikolajeva V, Babarykin D
Journal: Food Nut Sci 2, 868-877

Abstract: Plant material screening was performed to study anti-Helicobacter pylori activity in vitro using an agar diffusion method on Columbia blood agar. 33 substances, juices and plant extracts and 35 of their combinations were tested. Quince (Cydonia oblonga) juice demonstrated the strongest anti-H. pylori activity followed by cranberry juice. Concentrated apple juice, plum, red currant, black chokeberry, raspberry and bilberry juice also showed significant activity. Green tea and apple pomace extract as well as sweet flag rhizome, ginger and wild bergamot extract, cherry syrup, red beet juice and whey did not exhibit anti-Helicobacter activity. Quince juice in combination with bilberry, black chokeberry, red currant juice, green tea, sweet flag rhizome or apple pomace extract as well as cranberry juice in combination with sweet flag rhizome extract demonstrated a synergistic effect on inhibition of H. pylori. The obtained results offer new perspectives for development of functional anti-Helicobacter food product(s) for dietary management of H. pylori infection. The essential components of these products could be the most active juices and extracts like quince and cranberry juice supplemented with a corresponding synergist. Further studies are required to investigate the mechanism of antibacterial action of plant products and their efficacy in vivo.

Antimicrobial effect of cranberry juice and extracts

Posted: January 14, 2012
Authors: Cote, J. Caillet, S. Doyon, G. Dussault, D. Sylvain, J. F. Lacroix, M
Journal: Food Control 22: 8, 1413-1418.

Abstract: The antimicrobial effect of cranberry juice and of three cranberry extracts (water-soluble (E1) and apolar phenolic compounds (E2), and anthocyanins (E3)) was investigated against seven bacterial strains (Enterococcus faecium resistant to vancomycin (ERV), Escherichia coli O157:H7 EDL 933, Escherichia coli ATCC 25922, Listeria monocytogenes HPB 2812, Pseudomonas aeruginosa ATCC 15442, Salmonella Typhimurium SL1344, and Staphylococcus aureus ATCC 29213). Each cranberry sample was analyzed to determine the minimum inhibitory concentration (MIC) and the maximal tolerated concentration (MTC) at neutral pH. The results, reported in micro g phenol/mL, indicated that all the bacterial strains, both Gram-positive and Gram-negative, were selectively inhibited by the cranberry phenolic compounds. The extract rich in water-soluble phenolic compounds caused the most important growth inhibitions. The bacteria ERV, and to a lesser degree, P. aeruginosa, S. aureus and E. coli ATCC 25922, were the most sensitive to the antimicrobial activity of extract E1. The growth of P. aeruginosa and E. coli ATCC was also affected by the presence of the anthocyanin-rich cranberry extract E3, although the observed antibacterial effect was not as important as with extract E1. In general, L. monocytogenes, E. coli O157:H7 and S. Typhimurium were the most resistant to the antibacterial activity of the cranberry extracts. Within 30 min of exposure with pure neutralized cranberry juice, L. monocytogenes and ERV were completely inactivated.

Cranberry and Grape Juices Affect Tight Junction Function and Structural Integrity of Rotavirus-Infected Monkey Kidney Epithelial Cell Monolayers

Posted: January 14, 2012
Authors: Lipson SM, Gordon RE, Ozen FS, Karthikeyan L, Kirov N, Stotzky G
Journal: Food Environ Virol 3:46–54

Abstract: Cranberry juice (CJ) and grape juice (GJ) from Vaccinium macrocarpon and Vitis labrusca, respectively, and purified proanthocyanidins (PACs) from these species are recognized to possess antiviral activity. The effects of CJ and GJ on tight junction (TJ) structure and function among rotavirus-infected monkey kidney epithelial cells (MA-104) in monolayer cultures were evaluated. Antiviral activity by cranberry PACs of rotavirus in cell-free suspension was investigated by a rotavirus antigen [i.e., viral capsid protein 6 (VP6)] capture enzyme-linked immunosorbent assay (ELISA) and by transmission electron microscopy (TEM). MA-104 monolayers were treated with CJ, GJ, or cranberry juice cocktail (CJC) drink before inoculation with rotavirus. TJ function and structural integrity were measured by changes in transepithelial electrical resistance (TEER) and by reduction of signal intensity of the TJ &#945;-claudin 1 by immunofluorescence. The inhibitory activity of CJ and GJ on viral RNA synthesis, as a function of viral concentration, was determined by reverse transcription polymerase chain reaction (rtPCR). After 4 days, virus-infected monolayers pretreated with GJ (Concord and Niagara GJs) had TEER readings similar to uninfected controls. CJ and CJC also had a significant protective effect (P < 0.05) on TJ function, but to a lesser extent than GJ. Disorganization of TJ integrity commenced at 24- to 36-h post-viral inoculation, but this effect was reduced by pretreatment with CJ or GP of monolayer cultures. TEM showed aggregation of rotavirus by cranberry PACs. The destruction of rotavirus capsid proteins VP6, in cell-free suspension was inversely related to the concentration of cranberry PACs (C-PAC). Loss of rotavirus RNA by CJ or GJ was inversely related to viral infectivity titers. CJ, GJ, or PAC-associated antiviral activity has been linked to modifications in cellular physiologic events and to physical factors (e.g., PAC-mediated viral aggregation) that probably compromise viral infectivity. Multiple cell physiological and physical events must be considered when determining the mechanisms associated with the antiviral (i.e., rotavirus) activity of CJ, GJ, and PACs.

Impact of cranberry juice and proanthocyanidins on the ability of Escherichia coli to form biofilms

Posted: January 14, 2012
Authors: Pinzón-Arango PA, Holguin K, Camesano TA
Journal: Food Sci Biotechnol 20(5): 1315-1321

Abstract: The effects of cranberry juice cocktail (CJC) and proanthocyanidins (PACs) on biofilm formation were investigated. Escherichia coli strain HB101pDC1 and nonfimbriated strain HB101 were grown in 10 wt% CJC or 120 &#956;g/mL PACs for 12 consecutive cultures. Biofilm formation was investigated by incubating bacteria in 96-well polyvinyl chloride (PVC) plates and studying the optical density of the solution using the crystal violet method. We suspect that biofilm formation occurred due to non-specific interactions between the bacteria and the polymer. Both P-fimbriated E. coli HB101pDC1 and the non-fimbriated strain HB101 formed biofilms. E. coli strain HB101pDC1 formed a thicker and more mature biofilm. Cranberry juice inhibited biofilm formation after the first culture; however, for bacteria grown in PACs, a decrease in biofilm formation was observed with increasing number of cultures. The inhibitory effect was reversible. These results demonstrate that CJC is more effective than isolated PACs at preventing biofilm formation, possibly suggesting that other cranberry compounds also play a role in anti-biofilm activity.

Inhibition activity of wild berry juice fractions against Streptococcus pneumoniae binding to human bronchial cells

Posted: January 12, 2011
Authors: Huttunen S, Toivanen M, Arkko S, Ruponen M, Tikkanen-Kaukanen C.
Journal: Phytother Res 25(1):122-7

Abstract: Bacterial adhesion to the cell surface is a crucial step before infection can take place. Inhibition of bacterial binding offers a novel preventive approach against infections. Cranberry (Vaccinium macrocarpon Ait.) juice has been found to have antiadhesive activity against different bacteria. Streptococcus pneumoniae is an important pathogen and the most common cause for pneumonia, meningitis, and otitis media. In this study the inhibitory activity of cranberry (Vaccinium oxycoccos L.), bilberry (Vaccinium myrtillus L.) and crowberry (Empetrum nigrum and Empetrum hermaphroditum L.) juice fractions against pneumococcal binding was tested using human bronchial cells (Calu-3) as an adhesion model. In addition, the antimicrobial activity of the berry juice fractions was tested. It was found that the studied berry juice fractions had antiadhesion activity and cranberry juice was the most active. The adhesion inhibition activity of cranberry juice was nearly 90% at a concentration of 8.7mg/g of soluble solids. The antimicrobial activity of the studied berry juice fractions was found to be remarkable; pneumococcal growth was inhibited totally at a concentration of ~86mg/g. Both antiadhesion and antimicrobial activities were reduced after solid-phase extraction of the berry juices, which may suggest molecular synergistic effects of the berry juice molecules against S. pneumoniae. The findings indicate that cranberry, bilberry and crowberry juices have potential against pneumococcal infections.

Cranberry derived proanthocyanidins can prevent pathogen invasion of kidney epithelial cells

Posted: January 11, 2011
Authors: Tufenkji N, Rifai OJ, Harmidy K, Eydelnant IA
Journal: Food Res Int 43 (3):922-924

Abstract: The in vitro effectivity of cranberry derived proanthocyanidins (PACs) for the mitigation of kidney cell
infection by selected uro- and entero-pathogens is examined with an adhesion/invasion assay and confocal
microscopy. This study demonstrates that PACs effectively reduce invasion of canine kidney cells by
pathogenic bacteria: Escherichia coli CFT073 and O157:H7, Enterococcus faecalis 29212, and Pseudomonas
aeruginosa 10145. These effects demonstrate the potential for cranberry derived PACs as a useful tool in
the prevention of kidney infection

In vitro activity of cranberry extract against etiological agents of urinary tract infections

Posted: January 11, 2011
Authors: Rahbar M, Diba K
Journal: Afr J Pharm Pharmacol 4(5):286-288

Abstract: Cranberries have long been the focus of interest for their beneficial effects in preventing urinary tract infections (UTIs). The objective of this study was to determine in vitro activity of cranberry extract on common etiologic agents of urinary tract infections isolated from patients. Filter sterilized methanol extract of cranberry was prepared and used in the present study. The minimum inhibitory concentration (MIC) was evaluated for active crude extract. The MIC value of methanol extract were 0.391 mg/ml for
Enterobacter aerogenes and Staphylococcus aureus whereas the MIC of methanol extract of cranberry were 1.2500 and 0.0195 mg/ml for Escherichia coli and Klebsiella pneumoniae respectively. The lower MIC value of cranberry extract against K. pneumoniae in comparison to other three organisms suggests that K. pneumoniae showed greater sensitivity towards the extracts of the cranberry extract.

The structure of cranberry proanthocyanidins which inhibit adherence of uropatogenic Escherichia coli in vitro

Posted: January 7, 2011
Authors: Foo LY, Lu Y, Howell AB, Vorsa N.
Journal: Phytochemistry 54(2):173-181

Abstract: Ethyl acetate extracts of Sephadex LH20-purified proanthocyanidins of American cranberry (Vaccinium macrocarpon Ait.) exhibited potent biological activity by inhibiting adherence of uropathogenic isolates of P-fimbriated Escherichia coli bacteria to cellular surfaces containing a-Gal(1 4 4)b-Gal receptor sequences similar to those on epithelial cells in the urinary tract. The chemical structures of the proanthocyanidins were determined by 13C NMR, electrospray mass spectrometry, matrix-assisted
laser absorption time-of-flight mass spectrometry and by acid catalyzed degradation with phloroglucinol. The proanthocyanidin molecules consisted predominantly of epicatechin units with mainly DP of 4 and 5 containing at least one A-type linkage. The procyanidin A2 was the most common terminating unit occurring about four times as frequently as the epicatechin monomer

Cranberry synergies for dietary management of Helicobacter pylori infections

Posted: December 17, 2010
Authors: Vattem DA, Lin YT, Ghaedian R, Shetty K
Journal: Process Biochem 40(5):1583-1592

Abstract: Cranberry and its products are important components of the cranberry processing industry and have historically been associated with positive health benefits such as preventing urinary tract infections. These health benefits are associated with phenolic phytochemicals in the juice which are now known to have potential for inhibition of development and progression of cancer and cardiovascular diseases. Helicobacter pylori is an important human pathogen linked to peptic ulcer and now to cardiovascular diseases. Control of this pathogen using synthetic antimicrobials such as currently approved antibiotics has limitations due to potential development of resistance and low compliance. We believe a profile of antimicrobials compared to a single compound could be potentially more effective in managing H. pylori infections. We have investigated the effect of cranberry, blueberry and grape seed extracts on inhibiting H. pylori have been investigated. The ability of blueberry, grape seed and oregano extract on enhancing the antioxidant and anti-H. pylori activity of cranberry powder in a mixture was also investigated. The anti-H. pylori activity of the cranberry fruit extracts and their synergies correlated with antioxidant activity and the presence of biphenyls as well as polyphenolic phytochemicals. The anti-H. pylori activity of cranberry juice extract was significantly improved by its synergistic blending with blueberry, grape seed and oregano extract. The lower efficacy of purified phenolics in inhibiting H. pylori compared with fruit powder at similar dosage levels suggests a synergistic mode of functionality of these individual phenolics in whole food background. Consumption of blends of fruit juices with other fruit as well as herb extracts can impart unique functional attributes and could be an effective strategy in developing diet-based management of H. pylori infections as well as other oxidation linked diseases.

Inhibitory effects of cranberry polyphenols on formation and acidogenicity of Streptococcus mutans biofilms

Posted: December 17, 2010
Authors: Duarte S, Gregoire S, Singh AP, Vorsa N, Schaich K, Bowen WH, Koo H
Journal: FEMS Microbiol Lett 257(1):50-56

Abstract: Cranberry fruit is a rich source of polyphenols, and has shown biological activities against Streptococcus mutans. In the present study, we examined the influence of extracts of flavonols (FLAV), anthocyanins (A) and proanthocyanidins (PAC) from cranberry on virulence factors involved in Streptococcus mutans biofilm development and acidogenicity. PAC and FLAV, alone or in combination, inhibited the surface-adsorbed glucosyltransferases and F-ATPases activities, and the acid production by S. mutans cells. Furthermore, biofilm development and acidogenicity were significantly affected by topical applications of PAC and FLAV (P<0.05). Anthocyanins were devoid of any significant biological effects. The flavonols are comprised of mostly quercetin glycosides, and the PAC are largely A-type oligomers of epicatechin. Our data show that proanthocyanidins and flavonols are the active constituents of cranberry against S. mutans.

Synergism of cranberry phenolics with ellagic acid and rosmarinic acid for antimutagenic and DNA protection functions

Posted: December 17, 2010
Authors: Vattem DA, Jang HD, Levin R, Shetty K
Journal: J Food Biochem 30(1):98-116

Abstract: 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

Effects of cranberry extracts and ursolic acid derivatives on P-fimbriated Escherichia coli, COX-2 activity, pro-inflammatory cytokine release and the NF-kappabeta transcriptional response in vitro

Posted: December 16, 2010
Authors: Huang Y, Nikolic D, Pendland S, Doyle BJ, Locklear TD, Mahady GB
Journal: Pharmaceut Biol 47(1):18-25

Abstract: 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.

Cranberry constituents affect fructosyltransferase expression in Streptococcus mutans

Posted: November 22, 2010
Authors: Feldman M, Weiss E, Shemesh M, Ofek I, Bachrach G, Rozen R, Steinberg D
Journal: Alternative Ther Health Med 15(2):32-8

Abstract: 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.

Interference of cranberry constituents in cell-cell signaling system of Vibrio harveyi

Posted: November 22, 2010
Authors: Feldman M, Weiss EI, Ofek I, Steinberg D
Journal: Curr Microbiol 59(4):469-74

Abstract: 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

Loss of fimbrial adhesion with the addition of Vaccinum macrocarpon to the growth medium of P-fimbriated Escherichia coli

Posted: November 19, 2010
Authors: Ahuja S, Kaack B, Roberts J.
Journal: J Urol 159(2):559-62

Abstract: 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.

A high molecular mass constituent of cranberry juice inhibits helicobacter pylori adhesion to human gastric mucus.

Posted: November 17, 2010
Authors: Burger O, Ofek I, Tabak M, Weiss EI, Sharon N, Neeman I
Journal: FEMS Immunol Med Microbiol 29(4):295-301

Abstract: 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.

Impact of cranberry juice and proanthocyanidins (PACs) on the zeta potentials of Escherichia coli and uroepithelial cells

Posted: November 17, 2010
Authors: Liu YT, Pinzon-Arango PA, Camesano TA, Patil B, Murano P, Amiot-Carlin MJ
Journal: Acta Hort 841:259-264

Abstract: 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.

Influence of cranberry juice on attachment of Escherichia coli to glass

Posted: November 17, 2010
Authors: Allison DG, Cronin MA, Hawker J, Freeman S
Journal: J Basic Microbiol 40(1):3-6

Abstract: 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.

Media acidification by Escherichia coli in the presence of cranberry juice

Posted: November 17, 2010
Authors: Johnson BJ, Lin B, Rubin RA, Malanoski AP
Journal: BMC Res Notes 2:226.

Abstract: 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.

Microbial inhibitors of cranberries

Posted: November 17, 2010
Authors: Marwan AG, Nagel CW
Journal: J Food Sci 51(4):1009-1013

Abstract: 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%.

Anti-Escherichia coli adhesin activity of cranberry and blueberry juices

Posted: November 15, 2010
Authors: Ofek I, Goldhar J, Sharon N
Journal: Adv Exp Med Biol 408:179-83.

Abstract: No abstract

Does cranberry juice have antibacterial activity?

Posted: November 15, 2010
Authors: Lee YL, Owens J, Thrupp L and Cesario TC
Journal: JAMA 283(13):1691

Abstract: No abstract - Methods: We tested a 5-fold concentrated preparation of the juice to simulate the cranberry concentrate currently available commercially. The concentrate was diluted 1:1 with trypticase soy broth and adjusted to a pH of 7.0 to ensure that the results would not be confounded by the acidity of the medium. We added an inoculum of approximately 104 colony-forming units per milliliter from an overnight culture of a variety of American Type Culture Collection–quality control strains both to plain broth and the broth to which the cranberry juice had been added. Both cultures were incubated at 35°C and bacterial counts performed in duplicate at 90 minutes and 24 hours.

Anti-inflammatory activity of a high-molecular-weight cranberry fraction on macrophages stimulated by lipopolysaccharides from periodontopathogens

Posted: November 13, 2010
Authors: Bodet C, Chandad F, Grenier D
Journal: J Dent Res 85(3):235-9

Abstract: Periodontitis is a chronic inflammatory disease affecting oral tissues. The continuous, high production of cytokines by host cells triggered by periodontopathogens is thought to be responsible for the destruction of tooth-supporting tissues. Macrophages play a critical role in this host inflammatory response to periodontopathogens. The aim of this study was to investigate the effect of non-dialyzable material prepared from cranberry juice concentrate on the pro-inflammatory cytokine response of macrophages induced by lipopolysaccharides (LPS) from Actinobacillus actinomycetemcomitans, Fusobacterium nucleatum subsp. nucleatum, Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia, and Escherichia coli. Interleukin-1 beta (IL-1beta), IL-6, IL-8, tumor necrosis factor alpha (TNF-alpha), and Regulated on Activation Normal T-cell Expressed and Secreted (RANTES) production by macrophages treated with the cranberry fraction prior to stimulation by LPS was evaluated by ELISA. Our results clearly indicate that the cranberry fraction was a potent inhibitor of the pro-inflammatory cytokine and chemokine responses induced by LPS. This suggests that cranberry constituents may offer perspectives for the development of a new therapeutic approach to the prevention and treatment of periodontitis.

Cranberry extract inhibits low density lipoprotein oxidation

Posted: November 13, 2010
Authors: Wilson T, Porcari JP, Harbin D
Journal: Life Sci 62(24):A381-6

Abstract: Cranberry juice consumption is often used for the treatment of urinary tract infections, but the effect of cranberry juice on heart disease has not been investigated. We evaluated how a cranberry extract containing 1,548 mg gallic acid equivalents/liter (initial pH=2.50) affected low density lipoprotein (LDL) oxidation induced by 10 micromolar cupric sulfate. When LDL oxidation took place in the presence of diluted cranberry extracts, the formation of thiobarbituric acid reactive substances (TBARS) and LDL electrophoretic mobility were reduced. LDL electrophoretic migration was also reduced when the cranberry extract had a pH of 7.00 prior to dilution. This study suggests that cranberry extracts have the ability to inhibit the oxidative modification of LDL particles.

Effects of a high-molecular-weight cranberry fraction on growth, biofilm formation and adherence of Porphyromonas gingivalis

Posted: November 13, 2010
Authors: Labrecque J, Bodet C, Chandad F, Grenier D
Journal: J Antimicrob Chemother 58(2):439-43

Abstract: BACKGROUND: Porphyromonas gingivalis is a major aetiological agent of periodontitis, a destructive disease affecting the tooth-supporting tissues. Recent reports have indicated that high-molecular-weight molecules from cranberry juice concentrate can prevent the attachment of human pathogens to host tissues.

OBJECTIVES: The aim of the present study was to investigate the effect of non-dialysable material (NDM) prepared from cranberry juice concentrate on growth, biofilm formation and adherence properties of P. gingivalis.

METHODS: The effect of cranberry NDM on biofilm formation was studied using a polystyrene microplate assay and by scanning electron microscopy. The effect of cranberry NDM on the attachment properties of P. gingivalis was evaluated by a microplate assay in which mammalian proteins were immobilized into wells.

RESULTS: Our results indicated that cranberry NDM is a potent inhibitor of biofilm formation by P. gingivalis. However, it has no effect on growth and viability of bacteria. Cranberry NDM also prevented significantly the attachment of P. gingivalis to surfaces coated with type I collagen, fibrinogen or human serum.

CONCLUSIONS: Our data suggest that cranberry constituents may have a beneficial effect for the prevention and treatment of periodontitis by reducing the capacity of P. gingivalis to colonize periodontal sites.

Inhibiting interspecies coaggregation of plaque bacteria with a cranberry juice constituent

Posted: November 13, 2010
Authors: Weiss EI, Lev-Dor R, Kashamn Y, Goldhar J, Sharon N, Ofek I
Journal: J Am Dent Assoc 129(12):1719-23

Abstract: Dental plaque stability depends on bacterial adhesion to acquired pellicle, and on interspecies adhesion (or coaggregation). A high-molecular-weight cranberry constituent at 0.6 to 2.5 milligrams per milliliter reversed the coaggregation of 49 (58 percent) of 84 coaggregating bacterial pairs tested. It acted preferentially on pairs in which one or both members are gram-negative anaerobes frequently involved in periodontal diseases. Thus, the anticoaggregating cranberry constituent has the potential for altering the subgingival microbiota, resulting in conservative control of gingival and periodontal diseases. However, the high dextrose and fructose content of the commercially available cranberry juice makes it unsuitable for oral hygiene use, and the beneficial effect of the high-molecular-weight constituent requires animal and clinical studies.

Inhibition of Helicobacter pylori adhesion to human gastric mucus by a high-molecular-weight constituent of cranberry juice.

Posted: November 13, 2010
Authors: Burger O, Weiss E, Sharon N, Tabak M, Neeman I and Ofek I
Journal: Crit Rev Food Sci Nutr 42(3 Suppl):279-84

Abstract: A high-molecular-weight constituent of cranberry juice has been found to inhibit the sialyllactose specific adhesion of Helicobacter pylori strains to immobilized human mucus, erythrocytes, and cultured gastric epithelial cells. Different isolates of H. pylori differ in their affinity to the cranberry juice constituent. Cranberry juice may also inhibit adhesion of bacteria to the stomach in vivo, and may prove useful for the prevention of stomach ulcer that is caused by H. pylori.

Inhibition of host extracellular matrix destructive enzyme production and activity by a high-molecular-weight cranberry fraction

Posted: November 13, 2010
Authors: Bodet C, Chandad F, Grenier D
Journal: J Periodontal Res 42(2):159-68

Abstract: BACKGROUND AND OBJECTIVE: Periodontal diseases are a group of inflammatory disorders that are initiated by specific gram-negative bacteria and lead to connective tissue destruction. Proteolytic enzymes, including matrix metalloproteinases (MMPs) and elastase, produced by resident and inflammatory cells in response to periodontopathogens and their products, play a major role in gingival tissue destruction. The aim of this study was to investigate the effect of a high-molecular-weight fraction prepared from cranberry juice concentrate on MMP-3, MMP-9 and elastase activities, as well as on MMP production by human cells stimulated with lipopolysaccharide of Actinobacillus actinomycetemcomitans.

MATERIAL AND METHODS: MMP-3 and MMP-9 production by gingival fibroblasts and macrophages treated with the cranberry fraction and then stimulated with lipopolysaccharide was measured by enzyme-linked immunosorbent assay. MMP-3, MMP-9 and elastase activities in the presence of the cranberry fraction were evaluated using colorimetric or fluorogenic substrates. The changes in expression and phosphorylation state of fibroblast intracellular signaling proteins induced by A. actinomycetemcomitans lipopolysaccharide and the cranberry fraction were characterized by antibody microarrays.

RESULTS: The lipopolysaccharide-induced MMP-3 and MMP-9 responses of fibroblasts and macrophages were inhibited in a dose-dependent manner by the cranberry fraction. This fraction was found to inhibit fibroblast intracellular signaling proteins, a phenomenon that may lead to a down-regulation of activating protein-1 activity. MMP-3, MMP-9 and elastase activities were also efficiently inhibited by the cranberry fraction, even when it was used at low concentrations.

CONCLUSION: These results suggest that cranberry compounds offer promising perspectives for the development of novel host-modulating strategies for an adjunctive treatment of periodontitis.

Inhibition of periodontopathogen-derived proteolytic enzymes by a high-molecular-weight fraction isolated from cranberry

Posted: November 13, 2010
Authors: Bodet C, Piché M, Chandad F, Grenier D
Journal: J Antimicrob Chemother 57(4):685-90

Abstract: BACKGROUND: Porphyromonas gingivalis, Tannerella forsythia and Treponema denticola are three major aetiological agents of chronic periodontitis. The strong proteolytic activities of these bacteria are critical to their survival since their energy source is obtained from peptides and amino acids derived from proteins. In addition, proteases are important factors contributing to periodontal tissue destruction by a variety of mechanisms, including direct tissue degradation and modulation of host inflammatory responses.

OBJECTIVES: The aim of this study was to investigate the effect of non-dialysable material (NDM) prepared from cranberry juice concentrate on the proteolytic activities of P. gingivalis, T. forsythia and T. denticola.

METHODS: The effect of NDM on gingipain and dipeptidyl peptidase IV (DPP IV) activities of P. gingivalis, trypsin-like activity of T. forsythia and chymotrypsin-like activity of T. denticola was evaluated using synthetic chromogenic peptides. In addition, the capacity of P. gingivalis to degrade fluorescein-labelled type I collagen and fluorescein-labelled transferrin in the presence of NDM was evaluated by fluorometry.

RESULTS: NDM dose-dependently inhibited the proteinases of P. gingivalis, T. forsythia and T. denticola as well as type I collagen and transferrin degradation by P. gingivalis.

CONCLUSIONS: These results suggest that NDM has the potential to reduce either the proliferation of P. gingivalis, T. forsythia and T. denticola in periodontal pockets or their proteinase-mediated destructive process occurring in periodontitis.

Inhibitory activity of cranberry juice on adherence of type 1 and type P fimbriated Escherichia coli to eucaryotic cells

Posted: November 13, 2010
Authors: Zafriri D, Ofek I, Adar R, Pocino M, Sharon N

Abstract: Inhibition of bacterial adherence to bladder cells has been assumed to account for the beneficial action ascribed to cranberry juice and cranberry juice cocktail in the prevention of urinary tract infections (A. E. Sobota, J. Urol. 131:1013-1016, 1984). We have examined the effect of the cocktail and juice on the adherence of Escherichia coli expressing surface lectins of defined sugar specificity to yeasts, tissue culture cells, erythrocytes, and mouse peritoneal macrophages. Cranberry juice cocktail inhibited the adherence of urinary isolates expressing type 1 fimbriae (mannose specific) and P fimbriae [specific for alpha-D-Gal(1----4)-beta-D-Gal] but had no effect on a diarrheal isolate expressing a CFA/I adhesin. The cocktail also inhibited yeast agglutination by purified type 1 fimbriae. The inhibitory activity for type 1 fimbriated E. coli was dialyzable and could be ascribed to the fructose present in the cocktail; this sugar was about 1/10 as active as methyl alpha-D-mannoside in inhibiting the adherence of type 1 fimbriated bacteria. The inhibitory activity for the P fimbriated bacteria was nondialyzable and was detected only after preincubation of the bacteria with the cocktail. Cranberry juice, orange juice, and pineapple juice also inhibited adherence of type 1 fimbriated E. coli, most likely because of their fructose content. However, the two latter juices did not inhibit the P fimbriated bacteria. We conclude that cranberry juice contains at least two inhibitors of lectin-mediated adherence of uropathogens to eucaryotic cells. Further studies are required to establish whether these inhibitors play a role in vivo.

A-type cranberry proanthocyanidins and uropathogenic bacterial anti-adhesion activity

Posted: November 10, 2010
Authors: Howell AB, Reed JD, Krueger CG, Winterbottom R, Cunningham DG, Leahy M
Journal: Phytochemistry 66(18):2281-91

Abstract: Clinical, epidemiological and mechanistic studies support the role of cranberry (Vaccinium macrocarpon Ait.) in maintaining urinary tract health. Cranberry proanthocyanidins contain A-type linkages and have been associated with preventing adhesion of P-fimbriated uropathogenic Escherichia coli to uroepithelial cells. It is not known if the presence of the A-type linkage is a prerequisite for anti-adhesion activity. Other commercial sources of proanthocyanidins with all B-type linkages have not previously been screened for this activity. The goals of this study were to compare the in vitro anti-adhesion activity of A-linked proanthocyanidins from cranberry juice cocktail with the anti-adhesion activities of B-linked proanthocyanidins from commercial grape and apple juices, green tea and dark chocolate, and determine if anti-adhesion activity is detectable in human urine following consumption of single servings of each commercial food product. Structural heterogeneity and presence of the A-type linkage in cranberry proanthocyanidins was confirmed utilizing MALDI-TOF/MS and DI/ESI MS, as was the presence of all B-type linkages in the proanthocyanidins from the other commercial products. The isolated A-type proanthocyanidins from cranberry juice cocktail elicited in vitro anti-adhesion activity at 60 microg/ml, the B-type proanthocyanidins from grape exhibited minor activity at 1200 microg/ml, while other B-type proanthocyanidins were not active. Anti-adhesion activity in human urine was detected following cranberry juice cocktail consumption, but not after consumption of the non-cranberry food products. Results suggest that presence of the A-type linkage in cranberry proanthocyanidins may enhance both in vitro and urinary bacterial anti-adhesion activities and aid in maintaining urinary tract health.

Cranberry products inhibit adherence of p-fimbriated Escherichia coli to primary cultured bladder and vaginal epithelial cells.

Posted: November 10, 2010
Authors: Gupta K, Chou MY, Howell A, Wobbe C, Grady R, Stapleton AE
Journal: J Urol 177(6):2357-60

Abstract: PURPOSE: Cranberry proanthocyanidins have been identified as possible inhibitors of Escherichia coli adherence to uroepithelial cells. However, little is known about the dose range of this effect. Furthermore, it has not been studied directly in the urogenital system. To address these issues we tested the effect of a cranberry powder and proanthocyanidin extract on adherence of a P-fimbriated uropathogenic E. coli isolate to 2 new urogenital model systems, namely primary cultured bladder epithelial cells and vaginal epithelial cells.

MATERIALS AND METHODS: E. coli IA2 was pre-incubated with a commercially available cranberry powder (9 mg proanthocyanidin per gm) or with increasing concentrations of proanthocyanidin extract. Adherence of E. coli IA2 to primary cultured bladder epithelial cells or vaginal epithelial cells was measured before and after exposure to these products.

RESULTS: Cranberry powder decreased mean adherence of E. coli IA2 to vaginal epithelial cells from 18.6 to 1.8 bacteria per cell (p <0.001). Mean adherence of E. coli to primary cultured bladder epithelial cells was decreased by exposure to 50 mug/ml proanthocyanidin extract from 6.9 to 1.6 bacteria per cell (p <0.001). Inhibition of adherence of E. coli by proanthocyanidin extract occurred in linear, dose dependent fashion over a proanthocyanidin concentration range of 75 to 5 mug/ml.

CONCLUSIONS: Cranberry products can inhibit E. coli adherence to biologically relevant model systems of primary cultured bladder and vaginal epithelial cells. This effect occurs in a dose dependent relationship. These findings provide further mechanistic evidence and biological plausibility for the role of cranberry products for preventing urinary tract infection.

Effects of cranberry juice on uropathogenic Escherichia coli in vitro biofilm formation

Posted: November 10, 2010
Authors: Di Martino P, Agniel R, Gaillard JL, Denys P
Journal: J Chemother 17(5):563-5

Abstract: No abstract

Influence of cranberry phenolics on glucan synthesis by glucosyltransferases and Streptococcus mutans acidogenicity

Posted: November 10, 2010
Authors: Gregoire S, Singh AP, Vorsa N, Koo H
Journal: J Appl Microbiol 103(5):1960-8

Abstract: "AIMS: To investigate the influence of several phenolic compounds isolated from cranberry fruit (Vaccinium macrocarpon) on some of the virulence properties of Streptococcus mutans associated with glucan synthesis and acidogenicity.

METHODS AND RESULTS: Individual phenolic acids, flavonols and proanthocyanidins were isolated by semi-preparative high-performance liquid chromatography from fresh cranberry fruit. Flavonols and proanthocyanidins (at 500 micromol l(-1)) moderately inhibited the activity of surface-adsorbed glucosyltransferases (GTFs) B and C and F-ATPases (15-35% inhibition; P < 0.05), and also disrupted acid production by S. mutans cells without affecting bacterial viability. Phenolic acids displayed minimal biological effects. Quercetin-3-arabinofuranoside, myricetin and procyanidin A2 displayed the most inhibition of S. mutans virulence traits; a combination of these compounds displayed enhanced effects.

CONCLUSIONS: Specific flavonoids from cranberries exhibit statistically significant but moderate biological activity against S. mutans. The biological activity of cranberry extracts may be a result from the complex mixture of flavonoids rather than a single active compound.

SIGNIFICANCE AND IMPACT OF STUDY: This is the first study to identify the bioactive constituents in cranberry against an oral bacterium using highly purified isolated compounds. The combined effects of specific flavonols and proanthocyanidins from cranberry on GTFs activity, acid production and acid tolerance of S. mutans make them attractive compounds to fully explore for their anti-biofilm and cariostatic properties."

Prevention of nonspecific bacterial cell adhesion in immunoassays by use of cranberry juice.

Posted: November 10, 2010
Authors: Johnson-White B, Buquo L, Zeinali M, Ligler FS
Journal: Anal Chem 78(3):853-7

Abstract: The ability of Vaccinum macrocarpon, the North American cranberry, to prevent bacterial adhesion has been used to advantage in the prevention of urinary tract infections and has recently been described for the prevention of adhesion of bacteria responsible for oral infections and stomach ulcers. This report documents the ability of cranberry juice to reduce nonspecific adhesion of bacteria to the borosilicate glass microscope slides used in an immunoarray biosensor format. Nonspecific binding of analytes in the array sensor leads to high background signals that cause increased detection limits and false positives. Reduction in background-to-signal ratios can be seen as the juice concentration is increased from 0 to 50% of the sample. This impact cannot be duplicated with grape, orange, apple, or white cranberry juice. Sugar content and pH have been eliminated as the agents in the juice responsible for the anti-adhesive activity.

Antiviral effects on bacteriophages and rotavirus by cranberry juice.

Posted: November 9, 2010
Authors: Lipson SM, Sethi L, Cohen P, Gordon RE, Tan IP, Burdowski A, Stotzky G.
Journal: Phytomedicine 14(1):23-30

Abstract: Studies were undertaken to investigate the antiviral effects of comestible juices, especially cranberry juice, on non-related viral species. After exposure of bacteriophage T2 to a commercially available cranberry (Vaccinium macrocarpon) juice cocktail (CJ), virus infectivity titer was no longer detectible. After a 60-min exposure to orange (OJ) and grapefruit juices (GJ), phage infectivity was reduced to 25-35% of control, respectively. Similar data were observed for the bacteriophage T4. CJ inactivation of phage T4 was rapid, dose-dependent, and occurred at either 4 or 23 degrees C. Neither pH nor differences in sugar/carbohydrate levels among the juices may be ascribed to the recognized antiviral effects. Further studies were performed to identify the occurrence of antiviral activity by CJ to a mammalian enteric virus. The treatment of the simian rotavirus SA-11 with a 20% CJ suspension was sufficient to inhibit hemagglutination. Under scanning and transmission electron microscopy, CJ was observed to inhibit the adsorption of phage T4 to its bacterial host cells and prevented the replication of rotavirus in its monkey kidney (MA-104) host cells, respectively. The data suggest, for the first time, a non-specific antiviral effect towards unrelated viral species (viz., bacteriophages T2 and T4 and the simian rotavirus SA-11) by a commercially available cranberry fruit juice drink.

Impact of cranberry on Escherichia coli cellular surface characteristics

Posted: November 9, 2010
Authors: Johnson BJ, Lin B, Dinderman MA, Rubin RA, Malanoski AP, Ligler FS
Journal: Biochem Biophys Res Comm 377(3):992-4

Abstract: The anti-adhesive effects of cranberry have been attributed to both interactions of its components with the surface of bacterial cells and to inhibition of p-fimbriae expression. Previous reports also suggested that the presence of cranberry juice changed the Gram stain characteristics of Escherichia coli. Here, we show that the morphology of E. coli is changed when grown in the presence of juice or extract from Vaccinium macrocarpon (cranberry). Gene expression analysis indicates the down regulation of flagellar basal body rod and motor proteins. Consistent with this finding and previous reports, the SEM images indicate a decrease in the visible p-fimbriae. The iodine used in Gram-staining protocols was found to interact differently with the bacterial membrane when cells were cultured in spiked media. Slight alterations in the Gram stain protocol demonstrated that culturing in the presence of cranberry juice does not change the Gram stain characteristics contradicting other reports.

An examination of the anti-adherence activity of cranberry juice on urinary and nonurinary bacterial isolates

Posted: November 8, 2010
Authors: Schmidt DR, Sobota AE
Journal: Microbios 55(224-225):173-81

Abstract: In a previous investigation it was demonstrated that cranberry juice cocktail was able to inhibit adherence in 77 clinical isolates of Escherichia coli obtained from patients with diagnosed urinary tract infections. This work has been extended to include clinical isolates of E. coli, Proteus, Klebsiella, Enterobacter and Pseudomonas isolated from urine, sputum, wound and stool. Bacterial strains isolated from urine adhere in greater numbers to urinary tract epithelial cells than organisms isolated from sputum, stool and wound sources. E. coli, isolated from urine, adheres to urinary epithelial cells, in numbers three times greater than E. coli isolated from other clinical sources, and thus appears to represent a unique population of cells in terms of adherence. Cranberry juice cocktail and urine and urinary epithelial cells obtained after drinking the cocktail all demonstrate antiadherence activity against Gram-negative rods isolated from urine and other clinical sources. Drinking the cocktail may be useful in managing urinary tract infections in certain patients.

Cranberry changes the physicochemical surface properties of E. coli and adhesion with uroepithelial cells

Posted: November 8, 2010
Authors: Liu Y, Gallardo-Moreno AM, Pinzon-Arango PA, Reynolds Y, Rodriguez G, Camesano TA.
Journal: Colloids Surface B 65(1):35-42

Abstract: Cranberries have been suggested to decrease the attachment of bacteria to uroepithelial cells (UC), thus preventing urinary tract infections, although the mechanisms are not well understood. A thermodynamic approach was used to calculate the Gibbs free energy of adhesion changes (DeltaG(adh)) for bacteria-UC interactions, based on measuring contact angles with three probe liquids. Interfacial tensions and DeltaG(adh) values were calculated for Escherichia coli HB101pDC1 (P-fimbriated) and HB101 (non-fimbriated) exposed to cranberry juice (0-27 wt.%). HB101pDC1 can form strong bonds with the Gal-Gal disaccharide receptor on uroepithelial cells, while HB101-UC interactions are only non-specific. For HB101 interacting with UC, DeltaG(adh) was always negative, suggesting favorable adhesion, and the values were insensitive to cranberry juice concentration. For the HB101pDC1-UC system, DeltaG(adh) became positive at 27wt.% cranberry juice, suggesting that adhesion was unfavorable. Acid-base (AB) interactions dominated the interfacial tensions, compared to Lifshitz-van der Waals (LW) interactions. Exposure to cranberry juice increased the AB component of the interfacial tension of HB101pDC1. LW interactions were small and insensitive to cranberry juice concentration. The number of bacteria attached to UC was quantified in batch adhesion assays and quantitatively correlated with DeltaG(adh). Since the thermodynamic approach should not agree with the experimental results when specific interactions are present, such as HB101pDC-UC ligand-receptor bonds, our results may suggest that cranberry juice disrupts bacterial ligand-UC receptor binding. These results help form the mechanistic explanation of how cranberry products can be used to prevent bacterial attachment to host tissue, and may lead to the development of better therapies based on natural products.

Direct adhesion force measurements between E. coli and human uroepithelial cells in cranberry juice cocktail

Posted: November 8, 2010
Authors: Liu Y, Pinzón-Arango PA, Gallardo-Moreno AM, Camesano TA
Journal: Mol Nutr Food Res 54(12):1744-1752

Abstract: Scope: Atomic force microscopy (AFM) was used to directly measure the nanoscale adhesion forces between P-fimbriated Escherichia coli (E. coli) and human uroepithelial cells exposed to cranberry juice, in order to reveal the molecular mechanisms by which cranberry juice cocktail (CJC) affects bacterial adhesion.Methods and results: Bacterial cell probes were created by attaching P-fimbriated E. coli HB101pDC1 or non-fimbriated E. coli HB101 to AFM tips, and the cellular probes were used to directly measure the adhesion forces between E. coli and uroepithelial cells in solutions containing: 0, 2.5, 5, 10, and 27 wt% CJC. Macroscale attachment of E. coli to uroepithelial cells was measured and correlated to nanoscale adhesion force measurements. The adhesion forces between E. coli HB101pDC1 and uroepithelial cells were dose-dependent, and decreased from 9.32+/-2.37 nN in the absence of CJC to 0.75+/-0.19 nN in 27 wt% CJC. Adhesion forces between E. coli HB101 and uroepithelial cells were low in buffer (0.74+/-0.18 nN), and did not change significantly in CJC (0.78+/-0.18 nN in 27 wt% CJC; P=0.794).Conclusion: Our study shows that CJC significantly decreases nanoscale adhesion forces between P-fimbriated E. coli and uroepithelial cells.

Inhibition of Helicobacter pylori and associated urease by oregano and cranberry phytochemical synergies.

Posted: November 8, 2010
Authors: Lin YT, Kwon YI, Labbe RG, Shetty K
Journal: Appl Environ Microbiol 71(12):8558-64

Abstract: Ulcer-associated dyspepsia is caused by infection with Helicobacter pylori. H. pylori is linked to a majority of peptic ulcers. Antibiotic treatment does not always inhibit or kill H. pylori with potential for antibiotic resistance. The objective of this study was to determine the potential for using phenolic phytochemical extracts to inhibit H. pylori in a laboratory medium. Our approach involved the development of a specific phenolic profile with optimization of different ratios of extract mixtures from oregano and cranberry. Subsequently, antimicrobial activity and antimicrobial-linked urease inhibition ability were evaluated. The results indicated that the antimicrobial activity was greater in extract mixtures than in individual extracts of each species. The results also indicate that the synergistic contribution of oregano and cranberry phenolics may be more important for inhibition than any species-specific phenolic concentration. Further, based on plate assay, the likely mode of action may be through urease inhibition and disruption of energy production by inhibition of proline dehydrogenase at the plasma membrane.

Role of cranberry juice on molecular-scale surface characteristics and adhesion behavior of Escherichia coli.

Posted: November 8, 2010
Authors: Liu Y, Black MA, Caron L, Camesano TA
Journal: Biotechnol Bioeng 93(2):297-305

Abstract: Cranberry juice has long been believed to benefit the prevention and treatment of urinary tract infections (UTIs). As the first step in the development of infection, bacterial adhesion is of great research interest, yet few studies have addressed molecular level adhesion in this context. P-fimbriated Escherichia coli play a major role in the development of a serious type of UTI, acute pyelonephritis. Experiments were conducted to investigate the molecular-scale effects of cranberry juice on two E. coli strains: HB101, which has no fimbriae, and the mutant HB101pDC1 which expresses P-fimbriae. Atomic force microscopy (AFM) was used to investigate both bacterial surface characteristics and adhesion forces between a probe surface (silicon nitride) and the bacteria, providing a direct evaluation of bacterial adhesion and interaction forces. Cranberry juice affected bacterial surface polymer and adhesion behavior after a short exposure period (<3 h). Cranberry juice affected the P-fimbriated bacteria by decreasing the adhesion forces between the bacterium and tip and by altering the conformation of the surface macromolecules on E. coli HB101pDC1. The equilibrium length of polymer (P-fimbriae) on this bacterium decreased from approximately 148 to approximately 48 nm upon being exposed to cranberry juice. Highly acidic conditions were not necessary for the prevention of bacterial adhesion, since neutralization of cranberry juice solutions to pH = 7.0 allowed us to observe differences in adhesion between the E. coli strains. Our results demonstrate molecular-level changes in the surfaces of P-fimbriated E. coli upon exposure to neutralized cranberry juice.

Berry phenolics selectively inhibit the growth of intestinal pathogens

Posted: November 6, 2010
Authors: Puupponen-Pimiä R, Nohynek L, Hartmann-Schmidlin S, Kähkönen M, Heinonen M, Määttä-Riihinen K, Oksman-Caldentey KM.
Journal: J Appl Microbiol 98(4):991-1000

Abstract: AIMS: To investigate the effects of berries and berry phenolics on pathogenic intestinal bacteria and to identify single phenolic compounds being responsible for antimicrobial activity.

METHODS AND RESULTS: Antimicrobial activity of eight Nordic berries and their phenolic extracts and purified phenolic fractions were measured against eight selected human pathogens. Pathogenic bacterial strains, both Gram-positive and Gram-negative, were selectively inhibited by bioactive berry compounds. Cloudberry and raspberry were the best inhibitors, and Staphylococcus and Salmonella the most sensitive bacteria. Phenolic compounds, especially ellagitannins, were strong inhibitory compounds against Staphylococcus bacteria. Salmonella bacteria were only partly inhibited by the berry phenolics, and most of the inhibition seemed to originate from other compounds, such as organic acids. Listeria strains were not affected by berry compounds, with the exception of cranberry. Phenolic compounds affect the bacteria in different mechanisms.

CONCLUSIONS: Berries and their phenolics selectively inhibit the growth of human pathogenic bacteria.

SIGNIFICANCE AND IMPACT OF THE STUDY: Antimicrobial properties of berries could be utilized in functional foods. Furthermore these compounds would be of high interest for further evaluation of their properties as natural antimicrobial agents for food and pharmaceutical industry

Fighting infectious diseases with inhibitors of microbial adhesion to host tissues

Posted: November 6, 2010
Authors: Sharon N, Ofek I
Journal: Crit Rev Food Sci Nutr 42(3 Suppl):267-72

Abstract: The majority of infectious diseases are initiated by the adhesion of pathogenic organisms to the tissues of the host. In many cases this adhesion is mediated by lectins present on the surface of the infectious organism that bind to complementary carbohydrates on the surface of the host tissues. Soluble carbohydrates recognized by the bacterial lectins block the adhesion of the bacteria to animal cells in vitro. Moreover, such carbohydrates have been shown to protect against experimental infection by lectin-carrying bacteria of different mammals, such as mice, rabbits, calves, and monkeys. Agents other than carbohydrates also block adhesion, as demonstrated with cranberry juice as well as with low and high molecular weight preparations isolated from the juice. Both kinds of preparation inhibited the adhesion in vitro of Escherichia coli to different animal cells. In addition, the high molecular weight material acted similarly on the adhesion of Helicobacter pylori to human gasrointenstinal cells, and on the coaggregation of oral bacteria. Furthermore, in limited clinical studies regular drinking of cranberry juice had a significant preventive effect on bacteriuria, and the high molecular weight constituent of the juices was also effective in decreasing the salivary level of Streptococus mutans, the major cause of tooth decay. Because the inhibitors of adhesion examined are not bactericidal, the selection of resistant inhibitor strains is unlikely to occur. Together, these findings may lead to new therapeutic strategies that are in dire need because of the world-wide increase in antibiotic resistant bacteria.

Susceptibility of Helicobacter pylori isolates to the antiadhesion activity of a high-molecular-weight constituent of cranberry

Posted: November 6, 2010
Authors: Shmuely H, Burger O, Neeman I, Yahav J, Samra Z, Niv Y, Sharon N, Weiss E, Athamna A, Tabak M, Ofek I
Journal: Diagn Microbiol Infect Dis 50(4):231-5

Abstract: The sensitivity of a large number of antibiotic-resistant and nonresistant Helicobacter pylori isolates to the antiadhesion effect of a high-molecular-mass, nondialysable constituent of cranberry juice was tested. Confluent monolayers of gastric cell line in microtiter plate wells were exposed to bacterial suspensions prepared from 83 H. pylori isolates from antibiotic-treated and untreated patients in the presence and absence of the cranberry constituent. Urease assay was used to calculate the percentage of adhesion inhibition. In two thirds of the isolates, adhesion to the gastric cells was inhibited by 0.2 mg/mL of the nondialysable material. There was no relationship between the antiadhesion effect of the cranberry material and metronidazole resistance in isolates from either treated or untreated patients (N=35). Only 13 isolates (16%) were resistant to both the nondialysable material and metronidazole, and 30 (36%) were resistant to the nondialysable material alone. There was no cross-resistance to the nondialysable material and metronidazole. These data suggest that a combination of antibiotics and a cranberry preparation may improve H. pylori eradication.

Anti-Escherichia coli adhesin activity of cranberry and blueberry juices.

Posted: November 5, 2010
Authors: Ofek I, Goldhar J, Zafriri D, Lis H, Adar R, Sharon N.
Journal: N Engl J Med 324(22):1599

Abstract: No abstract - The high-molecular-weight inhibitor of adhesin was partially purified from cranberry juice by gel-filtration chromatography. The product was heat-stable, resistant to trypsin, and nondialysable, and it inhibited the MR adhesin of al 20 urinary isolates tested in concentrations of 12 to 25 µg per milliliter. On the basis of these results, together with those of earlier studies, we suggest that the antiadhesive agents in juices from vaccinium berries may act in the gut (the source of most uropathogens), in the bladder, or both by preventing colonization of these sites.

Cranberry high molecular weight constituents promote Streptococcus sobrinus desorption from artificial biofilm

Posted: November 5, 2010
Authors: Steinberg D, Feldman M, Ofek I, Weiss EI
Journal: Int J Antimicrob Agents 5(3):247-51

Abstract: Dental biofilm harbouring oral bacteria is highly correlated with the progression of dental diseases. Disruption of biofilm formation via anti-adhesion agents is an alternative means to the antibacterial approach. Previous studies have shown that high molecular weight non-dialysable material (NDM) derived from cranberry juice inhibits the adhesion of Escherichia coli and the coaggregation of a variety of oral bacteria. In addition, it inhibits the formation of glucans and fructans synthesised by GTF and FTF. In the present study, we examined the anti-adhesion effect of NDM on S. sobrinus. NDM promoted desorption of S. sobrinus from biofilm in the presence and absence of extracellular glucans and fructans, although the effect was more pronounced in the absence of these polysaccharides. Precoating of the bacteria with NDM reduced their ability to form biofilm. Our results indicate that NDM could be exploited as an anti-biofilm agent.

Cranberry juice constituents affect influenza virus adhesion and infectivity

Posted: November 5, 2010
Authors: Weiss EI, Houri-Haddad Y, Greenbaum E, Hochman N, Ofek I, Zakay-Rones Z.
Journal: Antiviral Res 66(1):9-12

Abstract: Cranberry juice contains high molecular weight materials (NDM) that inhibit bacterial adhesion to host cells as well as the co-aggregation of many oral bacteria. Because of its broad-spectrum activity, we investigated NDM's potential for inhibiting influenza virus adhesion to cells, and subsequent infectivity. Hemagglutination (HA) of red blood cells (RBC) caused by representatives of both influenza virus A subtypes (H1N1)and H3N2) and the B type was inhibited by NDM at concentrations of 125 microg/ml or lower, which is at least 20-fold lower than that usually found in cranberry juice. A dose-response effect of NDM on HA was demonstrated. The infectivity of the A and B types was significantly reduced by preincubation with NDM (250 microg/ml), as reflected by the lack of cytopathic effect on Madine-Darby canine kidney (MDCK) cells and the lack of HA activity in the media of infected cells. The effect of NDM was also tested after A or B type viruses were allowed to adsorb to and penetrate the cells. Various levels of reduction in virus tissue culture infective dose TCID50 were observed. The effect was most pronounced when NDM was added several times to the infected MDCK cells. Our cumulative findings indicate that the inhibitory effect of NDM on influenza virus adhesion and infectivity may have a therapeutic potential.

Effect of a high-molecular-weight component of cranberry on constituents of dental biofilm

Posted: November 5, 2010
Authors: Steinberg D, Feldman M, Ofek I, Weiss EI
Journal: J Antimicrob Chemother 54(1):86-9

Abstract: BACKGROUND: Previous studies have shown that high molecular-weight non-dialysable material derived from cranberry juice (NDM) inhibits co-aggregation of a variety of oral bacteria.

OBJECTIVES: In the present study, we examined the effect of NDM on several constituents of the dental biofilm, glucosyltransferase (GTF) and fructosyltransferase (FTF), as well as on the adhesion of Streptococcus sobrinus.

RESULTS: The activity of immobilized and soluble GTF and FTF was inhibited by NDM (P > 0.05). NDM also inhibited adhesion of S. sobrinus to hydroxyapatite (P < 0.05).

CONCLUSIONS: Our results indicate that NDM may affect biofilm formation. One of the proposed mechanisms is via inhibition of extracellular polysaccharide synthesis, which promote the sucrose-dependent adhesion of oral bacteria as S. sobrinus.

Anti-Porphyromonas gingivalis and anti-inflammatory activities of A-type cranberry proanthocyanidins.

Posted: November 4, 2010
Authors: La VD, Howell AB, Grenier D
Journal: Antimicrob Agents Chemother 54(5):1778-84

Abstract: A-type cranberry proanthocyanidins (AC-PACs) have recently been reported to be beneficial for human health, especially urinary tract health. The effect of these proanthocyanidins on periodontitis, a destructive disease of tooth-supporting tissues, needs to be investigated. The purpose of this study was to investigate the effects of AC-PACs on various virulence determinants of Porphyromonas gingivalis as well as on the inflammatory response of oral epithelial cells stimulated by this periodontopathogen. We examined the effects of AC-PACs on P. gingivalis growth and biofilm formation, adherence to human oral epithelial cells and protein-coated surfaces, collagenase activity, and invasiveness. We also tested the ability of AC-PACs to modulate the P. gingivalis-induced inflammatory response by human oral epithelial cells. Our results showed that while AC-PACs neutralized all the virulence properties of P. gingivalis in a dose-dependent fashion, they did not interfere with growth. They also inhibited the secretion of interleukin-8 (IL-8) and chemokine (C-C motif) ligand 5 (CCL5) but did not affect the secretion of IL-6 by epithelial cells stimulated with P. gingivalis. This anti-inflammatory effect was associated with reduced activation of the nuclear factor-kappaB (NF-kappaB) p65 pathway. AC-PACs may be potentially valuable bioactive molecules for the development of new strategies to treat and prevent P. gingivalis-associated periodontal diseases.

Cranberry derived proanthocyanidins reduce bacterial adhesion to selected biomaterials.

Posted: November 4, 2010
Authors: Eydelnant IA, Tufenkji N

Abstract: Catheter associated urinary tract infections (CAUTI) linked with the uropathogens Escherichia coli (E. coli) and Enterococcus faecalis (E. faecalis) account for the majority of nosocomial infections acquired in the clinical environment. Because these infections develop following initial adhesion of the bacterial pathogens to the catheter surface, there is increased interest in developing effective methods to inhibit attachment of cells to biomaterials used in the manufacture of indwelling devices. High molecular weight proanthocyanidins (PAC) extracted from the North American cranberry (Vaccinium macrocarpon) were examined for their potential to reduce the initial adhesion of uropathogenic bacteria (E. coli CFT073 and E. faecalis 29212) to two model biomaterials, poly(vinyl chloride) (PVC) and polytetrafluoroethylene (PTFE). Well-controlled experiments conducted in a parallel-plate flow chamber (PPFC) demonstrated decreased attachment of both bacteria to PVC and PTFE when either the bacteria, biomaterial or both surfaces were treated with PAC. Most significant inhibition of bacterial adhesion was observed for the condition where both the bacteria and biomaterial surfaces were coated with PAC. Additional experiments conducted with nonbiological model particles demonstrate comparable extents of adhesion inhibition, supporting a nonbiospecific mechanism of PAC action. The results of this study are promising for the implementation of PAC in the clinical milieu for prevention of device associated infection as the proposed functional modification is independent of antibacterial mechanisms that may give rise to resistant strains.

Cranberry proanthocyanidins inhibit MMP production and activity

Posted: November 4, 2010
Authors: La VD, Howell AB, Grenier D
Journal: J Dent Res 88(7):627-32

Abstract: Matrix metalloproteinases (MMPs) produced by resident and inflammatory cells in response to periodontopathogens play a major role in periodontal tissue destruction. Our aim was to investigate the effects of A-type cranberry proanthocyanidins (AC-PACs) on: (i) the production of various MMPs by human monocyte-derived macrophages stimulated with Aggregatibacter actinomycetemcomitans lipopolysaccharide (LPS), and (ii) the catalytic activity of recombinant MMP-1 and MMP-9. The effects of AC-PACs on the expression of 5 protein kinases and the activity of nuclear factor-kappa B (NF-kappaB) p65 in macrophages stimulated with LPS were also monitored. Our results indicated that AC-PACs inhibited the production of MMPs in a concentration-dependent manner. Furthermore, the catalytic activity of MMP-1 and MMP-9 was also inhibited. The inhibition of MMP production was associated with reduced phosphorylation of key intracellular kinases and the inhibition of NF-kappaB p65 activity. AC-PACs thus show potential for the development of novel host-modulating strategies to inhibit MMP-mediated tissue destruction during periodontitis.

Cytoprotective effect of proanthocyanidin-rich cranberry fraction against bacterial cell wall-mediated toxicity in macrophages and epithelial cells.

Posted: November 4, 2010
Authors: La VD, Labrecque J, Grenier D
Journal: Phytother Res 23(10):1449-52

Abstract: Recent studies brought evidence regarding the potential beneficial effects of cranberry polyphenols for periodontal infections. In this study, we evaluated the capacity of a proanthocyanidin-rich cranberry fraction to protect macrophages and oral epithelial cells against cytotoxicity induced by bacterial components. U937 cells, differentiated into adherent macrophage-like cells, as well as oral epithelial cells were treated with cell wall or lipopolysaccharide preparations from periodontopathogens. Cell viability was monitored using a commercial MTT (3-[4,5-diethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay. The cytoprotective effect was evaluated by pre-incubating human cells with a proanthocyanidin-rich cranberry fraction prior to treatment with the bacterial components at toxic concentrations. Among the various bacterial components tested, Peptostreptotoccus micros cell wall was found to be the most toxic for macrophages and epithelial cells and was thus selected for further analyses. Treatment of monocyte-derived macrophages with cell wall of P. micros (20 microg/ml) decreased the cell viability by approximately 50%. Adding the cranberry fraction prior to treating cells with P. micros cell wall dose-dependently protected monocyte-derived macrophages from the toxic effect. A dose-dependent cytoprotective effect of the cranberry fraction was also observed with oral epithelial cells treated with P. micros cell wall. This study suggests that cranberry polyphenols may exert a protective effect for host cells against the toxicity induced by bacterial components

Influence of cranberry juice on glucan-mediated processes involved in Streptococcus mutans biofilm development.

Posted: November 4, 2010
Authors: Koo H, Nino de Guzman P, Schobel BD, Vacca Smith AV, Bowen WH.
Journal: Caries Res 40(1):20-27

Abstract: Cranberry juice (CJ) has biological properties that may provide health benefits. In this study, we investigated the influence of CJ (pH 5.5) on several activities in vitro associated with the development of Streptococcus mutans UA159 biofilms. The ability of CJ to influence the adherence of S. mutans to either saliva- (sHA) or glucan-coated hydroxyapatite (gsHA), and to inhibit the glucan production by purified glucosyltransferases adsorbed to sHA was determined. For the adherence assays, we used both uncoated and saliva-coated bacterial cells. Furthermore, we examined whether CJ interferes with the viability, development, polysaccharide composition and acidogenicity of S. mutans biofilms. A solution containing equivalent amounts of glucose, fructose and organic acids at pH 5.5 was used as negative control. The adherence of S. mutans (uncoated and saliva-coated) to either sHA or gsHA treated with 25% CJ (v/v) was remarkably reduced (40-85% inhibition compared to control: p < 0.05), indicating that CJ effectively blocked the bacterial adherence to binding sites in salivary pellicle and in glucans. In contrast, when the bacterial cells alone were treated with CJ they adhered to the similar untreated surfaces. Cranberry juice (25%, v/v) also inhibited the activities of surface-adsorbed GTF B and C (70-80% inhibition compared to control, p < 0.05). The effect of CJ on the viability of microorganisms in biofilms was not significant. Biofilm formation and accumulation were significantly reduced by topical applications of 25% CJ (v/v) twice daily with 1-min exposures (p < 0.05). The biomass and insoluble glucan content of the biofilms in addition to its acidogenicity were significantly reduced by cranberry treatments (p < 0.05). Our data show that cranberry juice inhibited glucan-mediated biofilm development and acid production, and holds promise as a natural product to prevent biofilm-related oral diseases.

Inhibitory effect of cranberry polyphenol on biofilm formation and cysteine proteases of Porphyromonas gingivalis

Posted: November 4, 2010
Authors: Yamanaka A, Kouchi T, Kasai K, Kato T, Ishihara K, Okuda K.
Journal: J Periodontal Res 42(6):589-592

Abstract: BACKGROUND AND OBJECTIVE: The purpose of this study was to investigate the effects of cranberry polyphenol fraction on biofilm formation and activities of Arg-gingipain and Lys-gingipain in Porphyromonas gingivalis. MATERIAL AND METHODS: The polyphenol fraction was prepared by using a glass column packed with Amberlite XAD 7HP and 70% aqueous ethanol as an elution solvent. RESULTS: Synergistic biofilm formation by P. gingivalis and Fusobacterium nucleatum was significantly inhibited by the polyphenol fraction at a concentration of 250 microg/mL compared with untreated controls (p < 0.01). Arg-gingipain and Lys-gingipain activities in P. gingivalis ATCC 33277 and FDC 381 were inhibited significantly at a polyphenol fraction concentration of > or = 1 microg/mL (p < 0.05). CONCLUSION: These findings indicate that the polyphenol fraction inhibits biofilm formation and the Arg-gingipain and Lys-gingipain activities of P. gingivalis.

Inhibitory effects of cranberry juice on attachment of oral streptococci and biofilm formation

Posted: November 4, 2010
Authors: Yamanaka A, Kimizuka R, Kato T, Okuda K
Journal: Oral Microbiol Immunol 19(3):150-4

Abstract: Cranberry juice is known to inhibit bacterial adhesion. We examined the inhibitory effect of cranberry juice on the adhesion of oral streptococci strains labeled with [3H]-thymidine to saliva-coated hydroxyapatite beads (s-HA). When the bacterial cells were momentarily exposed to cranberry juice, their adherence to s-HA decreased significantly compared with the control (P < 0.01). Their hydrophobicity also decreased dependently with the concentration of cranberry juice. We also evaluated the inhibitory effect of cranberry juice on biofilm formation. By using a microplate system, we found that the high molecular mass constituents of cranberry juice inhibited the biofilm formation of the tested streptococci. The inhibitory activity was related to the reduction of the hydrophobicity. The present findings suggest that cranberry juice component(s) can inhibit colonization by oral streptococci to the tooth surface and can thus slow development of dental plaque.

A-Type proanthocyanidin trimers from cranberry that inhibit adherence of uropathogenic P-fimbriated Escherichia coli.

Posted: November 2, 2010
Authors: Foo LY, Lu Y, Howell AB, Vorsa N.
Journal: J Nat Prod 63:1225-1228

Abstract: Three proanthocyanidin trimers possessing A-type interflavanoid linkages, epicatechin-(4beta-->6)-epicatechin-(4beta-->8, 2beta-->O-->7)-epicatechin (4), epicatechin-(4beta-->8, 2beta-->O-->7)-epicatechin-(4beta-->8)-epicatechin (5), and epicatechin-(4beta-->8)-epicatechin-(4beta-->8, 2beta-->O-->7)-epicatechin (6), were isolated from the ripe fruits of Vaccinium macrocarpon (cranberry) and prevented adherence of P-fimbriated Escherichia coli isolates from the urinary tract to cellular surfaces containing alpha-Gal(1-->4)beta-Gal receptor sequences similar to those on uroepithelial cells. The structure of 4 was elucidated by a combination of spectroscopic methods and acid-catalyzed degradation with phloroglucinol. Also isolated were the weakly active epicatechin-(4beta-->8, 2beta-->O-->7)-epicatechin (procyanidin A2) (3) and the inactive monomer epicatechin (1) and the inactive dimer epicatechin-(4beta-->8)-epicatechin (procyanidin B2) (2).

Growth inhibitory action of cranberry on Helicobacter pylori.

Posted: November 2, 2010
Authors: Matsushima M, Suzuki T, Masui A, Kasai K, Kouchi T, Takagi A, Shirai T, Mine T
Journal: J Gastroenterol Hepatol 23(Suppl 2):S175-80

Abstract: BACKGROUND AND AIM: Cranberry is a fruit that originated in North America, and it has been used by Native Americans for bacterial infections. Recent studies have revealed it to be effective for preventing refractory urinary infections, while also suggesting that it plays a possible role in the eradication of Helicobacter pylori (H. pylori).

METHODS: The H. pylori strains used in the present study were NCTC11637 and 11638. Sugar and organic acid-rich, and polyphenol-rich fractions were obtained from cranberry juice concentrate by Amberlite XAD7HP-column chromatography. The H. pylori growth inhibition was estimated by OD(660) and titration in liquid culture, and by an agar dilution plate method. The shapes of the bacteria were analyzed by scanning electron microscopy.

RESULTS: Cranberry extract suppressed bacterial proliferation in a dose-dependent manner. In the comparison with other juices, polyphenol-rich fruits (cranberries, blueberries, and red grapes) showed similar growth inhibitory activity, whereas polyphenol-poor fruits (oranges, pineapples, apples, and white grapes) did not show any activity. The polyphenol-rich fraction of cranberry maintained the H. pylori-growth inhibitory activity. More bacteria in a coccoid form were observed after culture with cranberry.

CONCLUSION: Cranberry extract inhibited H. pylori proliferation and it is suggested that polyphenols are responsible for this action. The morphological analysis suggested that cranberry induces H. pylori to develop a coccoid form, thereby inhibiting its growth bacteriostatically. Further basic studies to clarify these mechanisms in combination with in vivo studies are needed.

Inhibition of Helicobacter pylori in vitro by various berry extracts, with enhanced susceptibility to clarithromycin

Posted: November 2, 2010
Authors: Chatterjee A, Yasmin T, Bagchi D and Stohs SJ
Journal: Mol Cell Biochem 265(1-2):19-26

Abstract: The objective of this study was to evaluate the effects of various berry extracts, with and without clarithromycin on Helicobacter pylori. Resistance to clarithromycin by H. pylori has been reported, leading to interest in alternatives/adjuncts to therapy with clarithromycin. H. pylori American type culture collection (ATCC) strain 49503 was grown, cell suspensions were made in
PBS and diluted 10-fold. One hundred &#956;l of the suspension was then incubated for 18 h with extracts of raspberry, strawberry, cranberry, elderberry, blueberry, bilberry, and OptiBerry R , a blend of the six berries, at 0.25–1% concentrations. Serially diluted cell suspensions were exposed for 1 h to clarithromycin at 15 &#956;g/ml. Ten &#956;l of bacterial samples from the 10–7 dilution tube
were plated and incubated for 18 h and the number of colonies were counted. Growth of H. pylori was confirmed by the CLO R test. All berry extracts significantly (p < 0.05) inhibited H. pylori, compared with controls, and also increased susceptibility of H. pylori to clarithromycin, with OptiBerry R demonstrating maximal effects.

Role of cranberry on bacterial adhesion forces and implications for Escherichia coli-uroepithelial cell attachment

Posted: November 2, 2010
Authors: Pinzon-Arango PA, Liu Y and Camesano TA
Journal: J Med Food 12(2):259-270

Abstract: Previous clinical research has suggested that the consumption of cranberry products prevents the adhesion of Escherichia coli to uroepithelial cells by causing changes in bacterial fimbriae. Atomic force microscopy was used to probe the adhesion forces between E. coli (nonfimbriated strain HB101 and the P-fimbriated variant HB101pDC1) and a model surface (silicon nitride), to determine the effect of growth in cranberry products on bacterial adhesion. Bacteria were grown in tryptic soy broth supplemented with either light cranberry juice cocktail (L-CJC) or cranberry proanthocyanidins (PACs). Growth of E. coli HB101pDC1 and HB101 in L-CJC or PACs resulted in a decrease in adhesion forces with increasing number of cultures. In a macroscale bacteria-uroepithelial cell adhesion assay a decrease in bacterial attachment was observed for E. coli HB101pDC1 grown in L-CJC or PACs. This effect was reversible because bacteria that were regrown in cranberry-free medium regained their ability to attach to uroepithelial cells, and their adhesion forces reverted to the values observed in the control condition. Exposure to increasing concentrations of L-CJC resulted in a decrease of bacterial attachment to uroepithelial cells for the P-fimbriated strain after L-CJC treatment (27% by weight) and after PACs treatment (345.8 microg/mL). Cranberry products affect the surface properties, such as fimbriae and lipopolysaccharides, and adhesion of fimbriated and nonfimbriated E. coli. The concentration of cranberry products and the number of cultures the bacteria were exposed to cranberry determines how much the adhesion forces and attachment are altered.

The effect of cranberry juice and cranberry proanthocyanidins on the infectivity of human enteric viral surrogates.

Posted: November 1, 2010
Authors: Su X, Howell AB, D'Souza DH
Journal: Food Microbiol 27(4):535-40

Abstract: The effect of cranberry juice (CJ) and cranberry proanthocyanidins (PAC) on the infectivity of human enteric virus surrogates, murine norovirus (MNV-1), feline calicivirus (FCV-F9), MS2(ssRNA) bacteriophage, and phiX-174(ssDNA) bacteriophage was studied. Viruses at high (approximately 7 log(10) PFU/ml) or low (approximately 5 log(10) PFU/ml) titers were mixed with equal volumes of CJ, 0.30, 0.60, and 1.20 mg/ml final PAC concentration, or water and incubated for 1 h at room temperature. Viral infectivity after treatments was evaluated using standardized plaque assays. At low viral titers, FCV-F9 was undetectable after exposure to CJ or the three tested PAC solutions. MNV-1 was reduced by 2.06 log(10) PFU/ml with CJ, and 2.63, 2.75, and 2.95 log(10) PFU/ml with 0.15, 0.30, and 0.60 mg/ml PAC, respectively. MS2 titers were reduced by 1.14 log(10) PFU/ml with CJ, and 0.55, 0.80, and 0.96 log(10) PFU/ml with 0.15, 0.30, and 0.60 mg/ml PAC, respectively. phi-X174 titers were reduced by 1.79 log(10) PFU/ml with CJ, and 1.95, 3.67, and 4.98 log(10) PFU/ml with PAC at 0.15, 0.30, and 0.60 mg/ml, respectively. Experiments using high titers showed similar trends but with decreased effects. CJ and PAC show promise as natural antivirals that could potentially be exploited for foodborne viral illness treatment and prevention.

Inhibitory effect of cranberry polyphenol on cariogenic bacteria

Posted: October 31, 2010
Authors: Yamanaka-Okada A, Sato E, Kouchi T, Kimizuka R, Kato T, Okuda K
Journal: Bull Tokyo Dent Coll 49(3):107-12

Abstract: The purpose of this study was to investigate the effect of cranberry polyphenol fraction on mutans streptococci. Hydrophobicity is an important factor in the adherence of bacteria to the tooth surface. We found that cranberry polyphenol fraction significantly decreased the hydrophobicity of Streptococcus sobrinus 6715, Streptococcus mutans MT8148R and JC2 in a dose-dependent manner (p<0.05). Biofilm formation by S. sobrinus 6715 and S. mutans MT8148R was inhibited by 100 microg/ml cranberry polyphenol fraction (p<0.01). When dosage was increased to 500 microg/ml, biofilm formation by S. mutans JC2 was significantly inhibited (p<0.05). Addition of 500 microg/ml cranberry polyphenol fraction to medium inhibited growth of S. mutans MT8148R compared with the control (p<0.05).

Cranberry cocktail juice, cranberry concentrates,

Posted: October 13, 2010
Authors: Lipson SM, Cohen P, Zhou J,Burdowski A
Journal: Mol Nutr Food Res 51:752-758

Abstract: Studies were performed to investigate the effect of several cranberry and grape juice extracts on the inhibition of reovirus infectivity following cell culture inoculation. Infectivity testing was performed utilizing cranberry juice extracts NutriCran-100TM and NutriCran-90TM. At 5% extract concentrations, titers were reduced by ca. 50%. Cranberry cocktail juice caused an infectivity loss of ca. 10%. We ascribe these data to higher concentrations of proanthocyanidins (PACs) in the cranberry extracts.
Further testing was performed utilizing purified high and low molecular weight cranberry PAC fractions (CB HMW and CB LMW, respectively), a cranberry flavonol glycoside (CB EToAc), cranberry anthocyanins (CB CA), and a grape PAC extract. Reovirus titers were reduced to undetectable levels at PAC concentrations f0.2%. CB CA had no effect on the inhibition of infectivity titers. Loss of infectivity titers was in the order: GP PACACB HMWACB LMWACB EToAc. Probe homogenization of CB HMWenhanced the extract to efficacy levels equal to that of grape PAC. Reovirus dsRNA segments were undetectable 96-h postcranberry cocktail juice pretreatment of MA-104 cell cultures. This study indicates an inhibition of reovirus infectivity titers by cranberry or grape juices or their purified PAC extracts. Viral inhibition probably occurs at the host cell surface.

Cranberry components inhibit interleukin-6, interleukin-8, and prostaglandin E production by lipopolysaccharide-activated gingival fibroblasts

Posted: October 11, 2010
Authors: Bodet C, Chandad F, Grenier D
Journal: Eur J Oral Sci 115(1):64-70

Abstract: Periodontitis is a chronic inflammatory disease that affects the tooth supporting tissues. Gingival fibroblasts are the most abundant cells in periodontal tissues and participate actively in the host inflammatory response to periodontopathogens, which is known to mediate local tissue destruction in periodontitis. The aim of this study was to investigate the effect of a proanthocyanidin-enriched cranberry fraction, prepared from cranberry juice concentrate, on inflammatory mediator production by gingival fibroblasts stimulated by the lipopolysaccharide (LPS) of Aggregatibacter actinomycetemcomitans. Interleukin (IL)-6, IL-8, and prostaglandin E(2) (PGE(2)) production by fibroblasts treated with the cranberry fraction and stimulated by A. actinomycetemcomitans LPS was evaluated by enzyme-linked immunosorbent assay. Changes induced by A. actinomycetemcomitans LPS and the cranberry fraction in the expression and phosphorylation state of fibroblast intracellular signaling proteins were characterized by antibody microarrays. The LPS-induced IL-6, IL-8, and PGE(2) responses of gingival fibroblasts were inhibited by treatment with the cranberry fraction. This fraction was found to inhibit fibroblast intracellular signaling proteins, a phenomenon that may lead to a down-regulation of activating protein-1 activity. Cranberry components also reduced cyclooxygenase 2 expression. This study suggests that cranberry juice contains molecules with interesting properties for the development of new host-modulating therapeutic strategies in the adjunctive treatment of periodontitis.

Antimicrobial action of the American cranberry constituents; phenolics, anthocyanins, and organic acids, against Escherichia coli O157:H7.

Posted: January 22, 2010
Authors: Lacombe A, Wu VC, Tyler S, Edwards K
Journal: Int J Food Microbiol 139(2010):102-7

Abstract: We investigated the antimicrobial effect of constituents of the American cranberry (Vaccinium macrocarpon); sugar plus organic acids, phenolics, and anthocyanins, against Escherichia coli O157:H7. Each fractional component was assayed over a 24-h period with 5-log initial inocula to determine the minimal inhibitory concentration (MIC), minimal bactericidal concentration (MBC), and log CFU/ml reductions, at their native pH and neutral pH. Each fraction produced significant reductions (P<0.05) at the native pH: MICs for sugars plus organic, phenolics, and anthocyanins were 5.6/2.6 Brix/acid (citric acid equivalents) 2.70g/L (gallic acid equivalent), and 14.80mg/L (cyanidin-3-glucoside equivalent), respectively. Sugars plus organic acids at native pH (3) produced a reduction below detectable limits (<1 log CFU/ml) compared to the control at 24h for 11.3/5.2 and 5.6/2.6 Brix/acid. Phenolics at native pH (4) produced reductions below detectable limits compared to the control at 24h and initial inocula for treatments of 5.40 and 2.70g/L. Anthocyanins at native pH (2) produced reductions below detectable limits for treatments of 29.15 and 14.80mg/L cyanidin-3-glucoside equivalents. Neutralized phenolics and anthocyanins had the same MIC and MBC as those at their native pH. Neutralized sugars plus organic acids did not inhibit bacterial growth compared to the control. Neutralized phenolics reduced bacteria below detectable limits in treatments of 5.40g/L and 2.70g/L compared to the control. Neutralized anthocyanins reduced bacterial growth below detectable limits at the concentration of 29.15mg/L, but at 14.80mg/L there was no significant reduction. Stationary-phase cells of E. coli O157:H7 were treated with 5% of each fraction in 0.8% NaCl for 20min and viewed under transmission electron microscopy. All fractions caused significant damage compared the control. Sugars plus organic acids caused visible osmotic stress, while phenolics and anthocyanins caused disintegration of the outer membrane.