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Urinary Tract Health and Antibacterial Benefits: In-Vitro

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

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Authors
Feldman M, Grenier D
Journal
J Appl Microbiol 113(2):438-47
Abstract

"Aims:  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:  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-1β, TNF-α, IL-6 and IL-8 in a macrophage model.

Conclusions:  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:  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

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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 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

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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

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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

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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

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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 μg/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

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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

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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

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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 Żuravit S·O·S(®) on the properties of uropathogenic Escherichia coli strains, their ability to form biofilm and its antioxidant properties.

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Authors
Wojnicz D, Sycz Z, Walkowski S, Gabrielska J, Aleksandra W, Alicja K, Anna SŁ, 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 (Żuravit 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. Żuravit 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.