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Polyphenol Characterization, Anti-Oxidant, Anti-Proliferation and Anti-Tyrosinase Activity of Cranberry Pomace

Posted: March 6, 2017
Authors: Rupasinghe V, Neir SV, Parmar I
Journal: Functional Foods in Health and Disease 6(11):754-68

Abstract: Background: Cranberry pomace (CP), an underutilized by-product from juice processing, contains a wide range of biologically active compounds that can be recovered and used in a variety of applications in functional foods and nutraceuticals. Methods: In this study, analytical chemical techniques such as solvent extractions and characterization of extracts in respect with their phenolic content were performed using ultra-high performance liquid chromatography mass spectrometry (UPLC-MS) and spectrophotometry. Crude CP extract and its phenolic acids, flavonols, anthocyanins and proanthocyanidins–rich fractions were then evaluated for their anti-oxidant capacity, tyrosinase inhibitory activity, and anti-proliferation activity against hepatocellular carcinoma HepG2 cells. Results: On a dry weight basis, the different CP fractions contained seven major anthocyanins (0.1-125 mg/g), six major phenolic acids (0.8-31 mg/g), seven flavonols (1-126 mg/g) and five flavan-3-ols (0.1-12 mg/g). Fractions rich in flavonols exhibited the most potent antioxidant capacities with ferric ion reducing antioxidant power values of 1.8-1.9 mmole/g and 2, 2-diphenyl-1-picrylhydrazyl radical scavenging IC50 values of 15.1-15.2 mg/L respectively. On the other hand, fractions rich in phenolic acids and flavan-3-ol monomers demonstrated the most potent anti-tyrosinase activity (IC50=6.1-6.2 mg/L) and anti-proliferative activity (IC50=7.8-15.8 mg/L). Generally, all the fractions exhibited a dose-response relationship in the selected biological activity assays.Conclusion: This study suggests an effective utilization of CP to obtain biologically active fractions with potential to be used in functional foods and nutraceuticals designed for the prevention of chronic diseases associated with oxidative stress.

Ability of Cranberry Proanthocyanidins in Combination with a Probiotic Formulation to Inhibit in Vitro Invasion of Gut Epithelial Cells by Extra-Intestinal Pathogenic E. Coli

Posted: March 1, 2017
Authors: Polewski MA, Krueger CG, Reed JD, Leyer G
Journal: Journal of Functional Foods; 2016. 25:123-134

Abstract: Cranberries and probiotics are individually considered as functional foods. This study evaluated the potential synergy between bioactive proanthocyanidins (c-PAC) derived from cranberries and probiotics on reducing the invasiveness of extra-intestinal pathogenic Escherichia coli (ExPEC) in a cell culture model. ExPEC can be a component of the gut microbiota in healthy individuals, and reducing the invasiveness of ExPEC is a potential means to lessen the risk of subsequent urinary tract infections (UTI), the most common bacterial infections in women. c-PAC (>92% A-type) concentrations greater than 36 micro g c-PAC/mL significantly (p<0.05) reduced ExPEC invasion, and was not inhibited by the presence of probiotics. Scanning electron microscopy suggests that the mechanism by which c-PAC prevent ExPEC invasion is by cross-linking surface virulence factors. A probiotic blend also significantly reduced invasion, albeit via a different mechanism. This study demonstrated the potential benefit of combining functional A-type c-PAC components in cranberry foods with probiotics.

Comparison of A-type Proanthocyanidins in Cranberry and Peanut Skin Extracts Using Matrix Assisted Laser Desorption Ionization-Time Of Flight Mass Spectrometry

Posted: March 1, 2017
Authors: Ye L, Neilson A, Sarnoski P, Ray WK, Duncan S
Journal: J Mol Genet Med. 2016;10(209):1747-086

Abstract: Cranberry products have long been used to treat urinary tract infections. It is believed that the A-type proanthocyanidins in cranberries contribute to this function. Peanut is one of the other, few food sources that primarily contain A-type proanthocyanidins. The skin on the outside of the peanut kernels (testa), which is treated as an agriculture waste product, contains high levels of A-type proanthocyanidins. In this study, an HPLC diol column separation method and MALDI-TOF MS were used to characterize and compare the proanthocyanidin compositions of peanut skins and cranberries. MALDI-TOF MS in linear mode was able to detect a group of proanthocyanidins with DP (degree of polymerization) 10 in peanut skin extract, but was only able to detect DP 8 in cranberry extract.The reflectron mode showed clusters of clear narrow peaks at DP 7 in peanut skin extract, while the highest DP resolved for cranberry extract was only 3 in reflectron mode. This might be due to the low response intensity of the cranberry samples with the current cleanup method and the matrix. Based on the resolved peaks in reflectron mode, peanut skins and cranberries have similar proanthocyanidins composition; they contain both A-type and B-type proanthocyanidins, with the A-type being predominant. This result may inspire future studies on the comparison of biological functions between peanut skins and cranberries and further comparison of their polymeric proanthocyanidin composition.

Cranberry Extract Standardized for Proanthocyanidins Alleviates Beta -Amyloid Peptide Toxicity by Improving Proteostasis Through HSF-1 in Caenorhabditis Elegans Model of Alzheimer's Disease

Posted: March 1, 2017
Authors: Guo H, Cao M, Zou S, Ye B, Dong Y
Journal: J Gerontol A Biol Sci Med Sci 71(12):1564-1573

Abstract: A growing body of evidence suggests that nutraceuticals with prolongevity properties may delay the onset of Alzheimer's disease (AD). We recently demonstrated that a proanthocyanidins-standardized cranberry extract has properties that prolong life span and promote innate immunity in Caenorhabditis elegans. In this article, we report that supplementation of this cranberry extract delayed A beta toxicity-triggered body paralysis in the C. elegans AD model. Genetic analyses indicated that the cranberry-mediated A beta toxicity alleviation required heat shock transcription factor (HSF)-1 rather than DAF-16 and SKN-1. Moreover, cranberry supplementation increased the transactivity of HSF-1 in an IIS-dependent manner. Further studies found that the cranberry extract relies on HSF-1 to significantly enhance the solubility of proteins in aged worms, implying an improved proteostasis in AD worms. Considering that HSF-1 plays a pivotal role in maintaining proteostasis, our results suggest that cranberry maintains the function of proteostasis through HSF-1, thereby protecting C. elegans against A beta toxicity. Together, our findings elucidated the mechanism whereby cranberry attenuated A beta toxicity in C. elegans and stressed the significance of proteostasis in the prevention of age-related diseases from a practical point of view.

Determination of Anthocyanins in Cherry and Cranberry by High-Performance Liquid Chromatography–Electrospray Lonization–Mass Spectrometry

Posted: March 1, 2017
Authors: Karaaslan NM, Yaman M
Journal: Eur Food Res Technol (2016) 242: 127

Abstract: Anthocyanins are a group of widespread natural phenolic compounds in vegetables and fruits. The anthocyanins have a wide range of applications due to the antioxidant, anticancer and anti-inflammatory properties. In this study, anthocyanins (delphinidin-3-o-glucoside, cyanidin-3-o-glucoside, pelargonidin-3-o-glucoside and malvidin-3-o-glucoside) in cherry and cranberry were determined using high-performance liquid chromatography–electrospray ionization–mass spectrometry (HPLC–ESI–MS). The anthocyanins were separated using gradient elution and a reserved-phase analytical column before identification by high-performance liquid chromatography–electrospray ionization–mass spectrometry. A high-performance liquid chromatography–electrospray ionization–mass spectrometry method was optimized for the determination of anthocyanins in cherry and cranberry. Furthermore, in this study, we investigated extraction conditions of fruit samples as well as determination of optimum HPLC–ESI–MS conditions. This study is novel in terms of simultaneously examining both optimization of HPLC parameters and extraction conditions. Obtained optimum conditions were used for the determination as the quantitative and qualitative analysis of anthocyanins in cherry and cranberry. The content of anthocyanins on the basis of wet weight in cherry and cranberry samples was determined for delphinidin-3-o-glucoside <d.l. (detection limit) and <d.l., for cyanidin-3-o-glucoside varied from 3.5 ± 0.4 to 8.3 ± 1.1 mg kg&#8722;1 (average 5.8 ± 0.8 mg kg&#8722;1) and 9.8 ± 1.4 to 18 ± 3.0 mg kg&#8722;1 (average 13.2 ± 1.8 mg kg&#8722;1), for pelargonidin-3-o-glucoside <d.l. and varied from 136 ± 19 to 233 ± 35 mg kg&#8722;1 (average 185.3 ± 28 mg kg&#8722;1), for malvidin-3-o-glucoside <d.l. and <d.l., respectively.

Study of the Impact of Cranberry Extract on the Virulence Factors and Biofilm Formation by Enterococcus Faecalis Strains Isolated from Urinary Tract Infections

Posted: March 1, 2017
Authors: Wojnicz D, Tichaczek-Goska D, Korzekwa K, Kicia M, Hendrich AB
Journal: Int J Food Sci Nutr 67(8):1005-16

Abstract: Drinking of cranberry fruit juice and application of commercial preparations containing the cranberry extracts are recommended in the prevention and treatment of urinary tract infections (UTIs), especially in women with recurrent UTIs. Many studies focus on the activity of cranberries against uropathogenic Escherichia coli (E. coli) strains. However, the knowledge of the cranberry effect on Gram-positive Enterococcus faecalis (E. faecalis) is limited. Therefore, the aim of our study was to establish the activity of commercial concentrated cranberry extract on the growth, virulence factors and biofilm formation of E. faecalis strains isolated from urine. Minimal inhibitory concentrations (MICs) of cranberry extract were determined by the broth microdilution method. Disc diffusion method was used to determine antimicrobial susceptibility. The impact of cranberry extract on bacterial survival, hydrophobicity, synthesis of lipase, lecithinase, DNase, hemolysin, gelatinase and biofilm mass was determined. Results show that cranberry extract inhibits the growth, enzymatic activities of bacteria and limits biofilm formation. The antibacterial activities of the studied cranberry extract confirm that it could be successfully used in prevention of UTIs caused by E. faecalis.

Ultrahigh Pressure Liquid Chromatography-Atmospheric Pressure Photoionization-Tandem Mass Spectrometry for the Determination of Polyphenolic Profiles in the Characterization and Classification of Cranberry-Based Pharmaceutical preparations and natural ext

Posted: March 1, 2017
Authors: Parets L, Alechaga E, Nunez O, Saurina J, Hernandez-Cassou S, Puignou L
Journal: Anal Methods 8(22):4363-4378

Abstract: Ultrahigh pressure liquid chromatography-atmospheric pressure photoionization-tandem mass spectrometry (UHPLC-APPI-MS/MS) was applied to the analysis and authentication of fruit-based products and pharmaceutical preparations. Two sub-2 micro m C18 reversed-phase columns, Syncronis (100x2.1 mm, 1.7 micro m) and Hypersil Gold (50x2.1 mm, 1.9 micro m), were proposed under gradient elution with 0.1% formic acid aqueous solution and methanol mobile phases for the determination of 29 polyphenols, allowing us to obtain polyphenolic profiles in less than 13.5 and 23.5 min, respectively. Several atmospheric pressure ionization (API) sources (H-ESI, APCI, and APPI) were compared. For dopant-assisted APPI, four organic solvents, toluene, acetone, chlorobenzene and anisole, were evaluated as dopants. Both H-ESI and acetone-assisted APPI were selected as the best ionization sources for the analysis of targeted polyphenols. Acceptable sensitivity (LOD values down to 0.5 micro g kg-1 in the best of cases), linearity (r2 higher than 0.995) and good precision (RSD values lower than 15.1%) and trueness (relative errors lower than 10.2%) were obtained using both UHPLC-API-MS/MS methods. A simple extraction procedure, consisting of sample sonication with acetone/water/hydrochloric acid (70:29.9:0.1 v/v/v) and centrifugation, was used. The proposed UHPLC-ESI-MS/MS and UHPLC-APPI-MS/MS methods with both C18 reversed-phase columns were then applied to the analysis of 32 grape-based and cranberry-based natural products and pharmaceutical preparations. Polyphenolic profile data were then analyzed by principal component analysis (PCA) to extract information on the most significant data contributing to the classification of natural extracts according to the type of fruit.

Urinary Clearance of Cranberry Flavonol Glycosides in Humans 2

Posted: March 1, 2017
Authors: Wang Y, Singh AP, Nelson HN, Kaiser AJ, Reker NC, Hooks TL, Wilson T, Vorsa N.
Journal: J Agric Food Chem 64(42):7931-7939

Abstract: Cranberry is reported to have health benefits, including prevention of urinary tract infections and other chronic diseases, due to the high content of polyphenols, including flavonols and flavan-3-ols. The aim of this study was to determine the clearance of flavonol glycosides and flavan-3-ols and/or their metabolites in human urine. Ten healthy women volunteers ingested 240 mL of cranberry juice containing flavonol glycosides. Urine samples were collected at 0, 90, 225, and 360 min postingestion. While flavan-3-ols were not detected, five flavonol glycosides common in cranberry were identified. Quercetin-3-galactoside, the most abundant cranberry flavonol, exhibited the highest peak urine concentration (Cmax) of 1315 pg/mg creatinine, followed by quercetin-3-rhamnoside, quercetin-3-arabinoside, myricetin-3-arabinoside, and myricetin-3-galactoside. Quercetin-3-arabinoside showed delayed clearance, Cmax at 237 min (Tmax), relative to other flavonols (90-151 min). Both aglycone and the conjugated sugar moiety structure mediate the flavonol's bioavailability. Interindividual variation for bioavailability and clearance is also apparent. Metabolites, e.g. glucoronides, were not detected.

Adjuvant effect of cranberry proanthocyanidin active fraction on antivirulent property of ciprofloxacin against Pseudomonas aeruginosa.

Posted: August 22, 2016
Authors: Vadekeetil A., Alexandar V., Chhibber S., Harjai K.
Journal: Microbial Pathogenesis; 2016. 90:98-103

Abstract: Quorum sensing inhibitors (QSIs) act as antivirulent agents since quorum sensing (QS) plays a vital role in regulating pathogenesis of Pseudomonas aeruginosa. However, application of single QSI may not be effective as pathogen is vulnerable to successful mutations. In such conditions, combination of QSIs can be exploited as there can be synergistic or adjuvant action. In the present study, we evaluated the antivirulence efficacy of combination of Vaccinium macrocarpon proanthocyanidin active fraction (PAF) and ciprofloxacin (CIP) at their sub-MICs using standard methods followed by analysis of their mode of action on QS using TLC and molecular docking. There was significant improvement in action of CIP when it was combined with PAF in reducing the QS controlled virulence factors (p<0.05), motilities and biofilm of P. aeruginosa. TLC profiles of QS signals [(Acyl homoserine lactone (AHL) and Pseudomonas quinolone signal (PQS))] indicated that CIP in combination with PAF, besides showing inhibitory action on production of AHLs, also modulated production and inactivation of PQS. Docking scores also supported the observation. We therefore hypothesize that PAF-CIP combination, having improved anti-virulence property; can be exploited as a potent drug pairing against P. aeruginosa.

Antibacterial activity of isolated phenolic compounds from cranberry (Vaccinium macrocarpon) against Escherichia coli.

Posted: August 22, 2016
Authors: Rodriguez-Perez, C. Quirantes-Pine, R. Uberos, J. Jimenez-Sanchez, C. Pena, A. Segura-Carretero, A.
Journal: Food and Function; 2016. 7(3):1564-1573.

Abstract: Phenolic compounds from a cranberry extract were isolated in order to assess their contribution to the antibacterial activity against uropathogenic strains of Escherichia coli (UPEC). With this purpose, a total of 25 fractions from a cranberry extract were isolated using semipreparative high performance liquid chromatography (HPLC) and characterized based on the results obtained by reversed-phase HPLC coupled to mass spectrometry detection. Then, the effects on UPEC surface hydrophobicity and biofilm formation of the cranberry extract as well as the purest fractions (a total of 13) were tested. As expected, the whole extract presented a powerful antibacterial activity against UPEC while the selected fractions presented a different behavior. Myricetin and quercitrin significantly decreased (p <0.05) E. coli biofilm formation compared with the control, while dihydroferulic acid glucuronide, procyanidin A dimer, quercetin glucoside, myricetin and prodelphinidin B led to a significant decrease of the surface hydrophobicity compared with the control. The results suggest that apart from proanthocyanidins, other compounds, mainly flavonoids, can act against E. coli biofilm formation and also modify UPEC surface hydrophobicity in vitro, one of the first steps of adhesion.

Beneficial effects of cranberry in the prevention of obesity and related complications: metabolic syndrome and diabetes - a review.

Posted: August 22, 2016
Authors: Kowalska, K. Olejnik, A.
Journal: Journal of Functional Foods; 2016. 20:171-181

Abstract: In recent years, obesity, metabolic syndrome and diabetes are becoming epidemic both in developed and developing countries. Recent experimental and clinical studies have raised interest in the potential health benefits of cranberry consumption in obesity and metabolic syndrome, which appear to be associated with the phytochemical composition of this fruit. Interestingly, cranberry administration has been reported to ameliorate dyslipidemia, hyperglycaemia and oxidative stress in individuals with the metabolic syndrome. This review focuses on the recent findings regarding beneficial effects of cranberry on obesity and metabolic syndrome, and discusses its potential mechanisms of action. The results of studies presented in this review have demonstrated that cranberry ameliorates insulin resistance and plasma lipid profile, decreases diet-induced weight gain and visceral obesity, and diminishes blood markers of oxidative stress. Thus, cranberry could be an effective and safe component of functional foods addressed for individuals with metabolic complications.

Cranberries (Oxycoccus quadripetalus) inhibit pro-inflammatory cytokine and chemokine expression in 3T3-L1 adipocytes.

Posted: August 22, 2016
Authors: Kowalska K., Olejnik A
Journal: Food chemistry. 196 (pp 1137-1143), 2016

Abstract: Oxidative stress and inflammation are involved in the development of obesity, type 2 diabetes and vascular complications. Systemic inflammation, as seen in obesity, is associated with high plasmatic levels of pro-inflammatory, pro-atherogenic and pro-thrombotic adipokines. Here we studied the effects of lyophilized cranberries (LCB) on the secretion and expression of PAI-1, IL-6, MCP-1 and leptin in mature 3T3-L1 adipocytes under baseline conditions and excessive inflammatory response elicitation by stimulation with H2O2. Our data demonstrated that LCB significantly reduced the expression and secretion of IL-6, MCP-1 and leptin, as well as suppressed the overexpression of PAI-1 induced by H2O2. Our findings suggested that LCB counteracted the stimulatory effect of H2O2 on secretion and expression of pro-inflammatory adipokines, implying a potential anti-inflammatory effect during the inflammatory process induced via oxidative stress in adipose tissue.

Cranberry derivatives enhance biofilm formation and transiently impair swarming motility of the uropathogen Proteus mirabilis HI4320.

Posted: August 22, 2016
Authors: O'May, C. Amzallag, O. Bechir, K. Tufenkji, N.
Journal: Can J Microbiol; 2016. 62(6):464-474.

Abstract: Proteus mirabilis is a major cause of catheter-associated urinary tract infection (CAUTI), emphasizing that novel strategies for targeting this bacterium are needed. Potential targets are P. mirabilis surface-associated swarming motility and the propensity of these bacteria to form biofilms that may lead to catheter blockage. We previously showed that the addition of cranberry powder (CP) to lysogeny broth (LB) medium resulted in impaired P. mirabilis swarming motility over short time periods (up to 16 h). Herein, we significantly expanded on those findings by exploring (i) the effects of cranberry derivatives on biofilm formation of P. mirabilis, (ii) whether swarming inhibition occurred transiently or over longer periods more relevant to real infections (~3 days), (iii) whether swarming was also blocked by commercially available cranberry juices, (iv) whether CP or cranberry juices exhibited effects under natural urine conditions, and (v) the effects of cranberry on medium pH, which is an indirect indicator of urease activity. At short time scales (24 h), CP and commercially available pure cranberry juice impaired swarming motility and repelled actively swarming bacteria in LB medium. Over longer time periods more representative of infections (~3 days), the capacity of the cranberry material to impair swarming diminished and bacteria would start to migrate across the surface, albeit by exhibiting a different motility phenotype to the regular "bull's-eye" swarming phenotype of P. mirabilis. This bacterium did not swarm on urine agar or LB agar supplemented with urea, suggesting that any potential application of anti-swarming compounds may be better suited to settings external to the urine environment. Anti-swarming effects were confounded by the ability of cranberry products to enhance biofilm formation in both LB and urine conditions. These findings provide key insights into the long-term strategy of targeting P. mirabilis CAUTIs.

Cranberry proanthocyanidins modulate reactive oxygen species in Barrett's and esophageal adenocarcinoma cell lines.

Posted: August 22, 2016
Authors: Weh, K. M. Aiyer, H. S. Howell, A. B. Kresty, L. A.
Journal: Journal of Berry Research; 2016. 6(2):125-136.

Abstract: BACKGROUND: We recently reported that a cranberry proanthocyanidin rich extract (C-PAC) induces autophagic cell death in apoptotic resistant esophageal adenocarcinoma (EAC) cells and necrosis in autophagy resistant cells. EAC is characterized by high morbidity and mortality rates supporting development of improved preventive interventions. OBJECTIVE: The current investigation sought to investigate the role of reactive oxygen species (ROS) in the context of C-PAC induced cell death. METHODS: Apanel of human esophageal cell lines of EAC or BE (Barrett's esophagus) origin were treated with C-PAC and assessed for ROS modulation using CellROXReg. Green reagent and the Amplex Red assay to specifically measure hydrogen peroxide levels. RESULTS: C-PAC significantly increased ROS levels in EAC cells, but significantly reduced ROS levels in CP-C BE cells. Increased hydrogen peroxide levels were also detected in C-PAC treated EAC cells and supernatant; however, hydrogen peroxide levels were significantly increased in medium alone, without cells, suggesting that C-PAC interferes or directly acts on the substrate. Hydrogen peroxide levels did not change in C-PAC treated CP-C BE cells. CONCLUSION: These experiments provide additional mechanistic insight regarding C-PAC induced cancer cell death through modulation of ROS. Additional research is warranted to identify specific ROS species associated with C-PAC exposure.

Cranberry product decreases fat accumulation in Caenorhabditis elegans.

Posted: August 22, 2016
Authors: Sun Q, Yue Y, Shen P, Yang JJ, Park Y.
Journal: Journal of Medicinal Food; 2016. 19(4):427-433.

Abstract: Cranberry phenolic compounds have been linked to many health benefits. A recent report suggested that cranberry bioactives inhibit adipogenesis in 3T3-L1 adipocytes. Thus, we investigated the effects and mechanisms of the cranberry product (CP) on lipid metabolism using the Caenorhabditis elegans (C. elegans) model. CP (0.016% and 0.08%) dose-dependently reduced overall fat accumulation in C. elegans (N2, wild type) by 43% and 74%, respectively, without affecting its pumping rates or locomotive activities. CP decreased fat accumulation in aak-2 (an ortholog of AMP-activated kinase alpha ) and tub-1 (an ortholog of TUBBY) mutants significantly, but only minimal effects were observed in sbp-1 (an ortholog of sterol response element-binding protein-1) and nhr-49 (an ortholog of peroxisome proliferator-activated receptor- alpha ) mutant strains. We further confirmed that CP downregulated sbp-1, cebp, and hosl-1 (an ortholog of hormone-sensitive lipase homolog) expression, while increasing the expression of nhr-49 in wild-type C. elegans. These results suggest that CP could effectively reduce fat accumulation in C. elegans dependent on sbp-1, cebp, and nhr-49, but not aak-2 and tub-1.

Critical reevaluation of the 4-(dimethylamino)cinnamaldehyde assay: cranberry proanthocyanidin standard is superior to procyanidin A2 dimer for accurate quantification of proanthocyanidins in cranberry products.

Posted: August 22, 2016
Authors: Krueger, C. G. Chesmore, N. Chen Xin Parker, J. Khoo, C. Marais, J. P. J. Shanmuganayagam, D. Crump, P. Reed, J. D.
Journal: Journal of Functional Foods; 2016. 22:13-19.

Abstract: The 4-(dimethylamino)cinnamaldehyde (DMAC) assay is currently used to quantify proanthocyanidin (PAC) content in cranberry products. In a multi-operator/multi-day study design, a cranberry proanthocyanidin (c-PAC) standard was compared to procyanidin A2 (ProA2) dimer for accurate quantification of PAC in commercial cranberry juices, lab generated cranberry blends and cranberry powders. The c-PAC standard reflects the structural heterogeneity of cranberry PAC degree of polymerization, hydroxylation pattern and ratios of 'A-type' to 'B-type' interflavanyl bonds. Use of the c-PAC standard to quantify PAC content in cranberry samples resulted in values that were 3.6 times higher than those determined by ProA2. Overall, there was no effect (P>0.05) of operator or day on estimation of PAC concentration. The adoption of c-PAC standard should be considered as an improvement over the use of ProA2 for accurate quantification of cranberry PAC. Improved standardization of bioactive PAC components in functional cranberry foods will aid in establishment of dosage guidelines.

Effect of cranberry (Vaccinium macrocarpon) oligosaccharides on the formation of advanced glycation end-products.

Posted: August 22, 2016
Authors: Sun J, Liu W, Ma H, Marais JPJ, Khoo C, Dain JA, Rowley DC, Seeram NP
Journal: Journal of Berry Research; 2016. 6(2):149-158

Abstract: BACKGROUND: The formation and accumulation of advanced glycation end-products (AGEs) are implicated in several chronic human illnesses including type-2 diabetes, renal failure, and neurodegenerative diseases. The cranberry (Vaccinium macrocarpon) fruit has been previously reported to show anti-AGEs effects, attributed primarily to its phenolic constituents. However, there is lack of similar data on the non-phenolic constituents found in the cranberry fruit, in particular, its carbohydrate constituents. Herein, a chemically characterized oligosaccharide-enriched fraction purified from the cranberry fruit was evaluated for its potential anti-AGEs and free radical scavenging effects. OBJECTIVE: The aim of this study was to evaluate the in vitro anti-AGEs and free radical scavenging effects of a chemically characterized oligosaccharide-enriched fraction purified from the North American cranberry (Vaccinium macrocarpon) fruit. METHOD: The cranberry oligosaccharide-enriched fraction was purified from cranberry hull powder and characterized based on spectroscopic and spectrometric (NMR, MALDI-TOF-MS, and HPAEC-PAD) data. The oligosaccharide-enriched fraction was evaluated for its anti-AGEs and free radical scavenging effects by the bovine serum albumin-fructose, and DPPH assays, respectively. RESULTS: Fractionation of cranberry hull material yielded an oligosaccharide-enriched fraction named Cranf1b-CL. The 1H NMR and MALDI-TOF-MS revealed that Cranf1b-CL consists of oligosaccharides ranging primarily from 6-mers to 9-mers. The monosaccharide composition of Cranf1b-CL was arabinose (25%), galactose (5%), glucose (47%) and xylose (23%). In the bovine serum albumin-fructose assay, Cranf1b-CL inhibited AGEs formation in a concentration-dependent manner with comparable activity to the synthetic antiglycating agent, aminoguanidine, used as the positive control (57 vs. 75%; both at 500 micro g/mL). In the DPPH free radical scavenging assay, Cranf1b-CL showed superior activity to the synthetic commercial antioxidant, butylated hydroxytoluene, used as the positive control (IC50=680 vs. 2200 micro g/mL, respectively). CONCLUSION: The in vitro anti-AGEs and free radical scavenging effects of cranberry oligosaccharides support previous data suggesting that these constituents may also contribute to biological effects of the whole fruit beyond its phenolic constituents alone. Also, this is the first study to evaluate a chemically characterized oligosaccharide fraction purified from the North American cranberry fruit for anti-AGEs and free radical scavenging properties.

Effect of glycated albumin and cranberry components on interleukin-6 and matrix metalloproteinase-3 production by human gingival fibroblasts

Posted: August 22, 2016
Authors: Tipton DA; Hatten AA; Babu JP; Dabbous MKh.
Journal: Journal of Periodontal Research. 51(2):228-36

Abstract: BACKGROUND AND OBJECTIVE: Gingival fibroblasts have the potential to participate in periodontal inflammation and breakdown, producing interleukin (IL)-6 and matrix metalloproteinase (MMP)-3. Advanced glycation end products (AGEs), formed during diabetic hyperglycemia, might aggravate periodontal inflammation. The cranberry contains anti-inflammatory polyphenols, which inhibit proinflammatory activities of lipopolysaccharide (LPS)- and IL-1beta-stimulated human cells. Little is known of its effects on gingival fibroblast IL-6 or MMP-3 production stimulated by AGEs. The objectives were to determine cranberry effects on IL-6 and MMP-3 production by gingival fibroblasts exposed to the representative AGE, glycated human serum albumin (G-HSA), or LPS +/- G-HSA. MATERIAL AND METHODS: Cranberry high molecular weight non-dialyzable material (NDM), was derived from cranberry juice. Normal human gingival fibroblasts were incubated with G-HSA or normal HSA or Porphyromonas gingivalis LPS (1 mug/mL) +/- G-HSA, in the presence or absence of preincubation with NDM. IL-6 and MMP-3 were measured by enzyme-linked immunosorbent assay. Data were analyzed using one-way analysis of variance and Scheffe's F procedure. RESULTS: IL-6 production was stimulated by G-HSA or LPS (p < 0.01), which was inhibited in both cases by NDM (p < 0.002). [G-HSA+LPS] synergistically stimulated IL-6 production (p < 0.0001), which was inhibited by NDM. MMP-3 levels were not stimulated by G-HSA but were decreased by LPS (p < 0.02). [G-HSA+LPS] increased MMP-3 production significantly, vs. LPS (p = 0.0005). NDM inhibited MMP-3 levels in the presence of G-HSA or LPS, and in the presence of [G-HSA+LPS] (p < 0.0001). CONCLUSIONS: G-HSA +/- LPS may have differential effects on IL-6 and MMP-3 production by human gingival fibroblasts, but both are inhibited by NDM. The study suggests that cranberry phenols may be useful in regulating the host response and perhaps treating periodontitis in patients with poorly controlled diabetes.

Effects of cranberry components on IL-1beta-stimulated production of IL-6, IL-8 and VEGF by human TMJ synovial fibroblasts.

Posted: August 22, 2016
Authors: Tipton DA; Christian J; Blumer A.
Journal: Archives of Oral Biology. 68:88-96, 2016 Aug

Abstract: OBJECTIVE: Osteoarthritis (OA) in the TMJ is characterized by deterioration of articular cartilage and secondary inflammatory changes. Interleukin-1beta (IL-1beta) stimulates IL-6, IL-8, and vascular endothelial growth factor (VEGF) in synovial fluid of TMJ with internal derangement and bony changes. The cranberry (Vaccinium macrocarpon) contains polyphenolic compounds that inhibit production of pro-inflammatory molecules by gingival cells in response to several stimulators. This study examined effects of cranberry components on IL-1beta-stimulated IL-6, IL-8, and VEGF production by human TMJ synovial fibroblast-like cells. DESIGN: Cranberry high molecular weight non-dialyzable material (NDM) was derived from cranberry juice. Human TMJ synovial fibroblast-like cells from joints with degenerative OA and an ankylosed TMJ without degeneration were incubated with IL-1beta (0.001-1nM)+/-NDM (25-250mug/ml) (2h preincubation). Viability was assessed via activity of a mitochondrial enzyme. IL-6, IL-8, and VEGF in culture supernatants were measured by ELISA; NF-kappaB and AP-1 transcription factors were measured in nuclear extracts via binding to specific oligonucleotides. DATA ANALYSIS: ANOVA and Scheffe's F procedure for post hoc comparisons. RESULTS: NDM did not affect cell viability but inhibited IL-1beta stimulated IL-6, IL-8, and VEGF production in all cell lines (p<0.05). NDM partially reduced nuclear levels of NF-kappaB and AP-1 (p<0.04), depending upon cell line and time of exposure to IL-1beta+NDM. CONCLUSION: Cranberry NDM inhibition of IL-1beta-stimulated IL- 6, IL-8, and VEGF production by TMJ synovial fibroblast-like cells suggests that cranberry components may be useful as a host modulatory therapeutic agent to prevent or treat inflammatory arthropathies of the TMJ.

Identification and quantification of novel cranberry-derived plasma and urinary (poly)phenols.

Posted: August 22, 2016
Authors: Feliciano R.P., Boeres A., Massacessi L., Istas G., Ventura M.R., Nunes Dos Santos C., Heiss C., Rodriguez-Mateos A.
Journal: Archives of Biochemistry and Biophysics. 599 (pp 31-41), 2016

Abstract: Cranberries are a rich source of (poly)phenols, in particular proanthocyanidins, anthocyanins, flavonols, and phenolic acids. However, little is known about their bioavailability in humans. We investigated the absorption, metabolism, and excretion of cranberry (poly)phenols in plasma and urine of healthy young men after consumption of a cranberry juice (787 mg (poly)phenols). A total of 60 cranberry-derived phenolic metabolites were identified using UPLC-Q-TOF-MS analysis with authentic standards. These included sulfates of pyrogallol, valerolactone, benzoic acids, phenylacetic acids, glucuronides of flavonols, as well as sulfates and glucuronides of cinnamic acids. The most abundant plasma metabolites were small phenolic compounds, in particular hippuric acid, catechol-O-sulfate, 2,3-dihydroxybenzoic acid, phenylacetic acid, isoferulic acid, 4-methylcatechol-O-sulfate, alpha-hydroxyhippuric acid, ferulic acid 4-O-sulfate, benzoic acid, 4-hydroxyphenyl acetic acid, dihydrocaffeic acid 3-O-sulfate, and vanillic acid-4-O-sulfate. Some benzoic acids, cinnamic acids, and flavonol metabolites appeared in plasma early, at 1-2 h post-consumption. Others such as phenylacetic acids, benzaldehydes, pyrogallols, catechols, hippuric and dihydrocinnamic acid derivatives appear in plasma later (Tmax 4-22 h). The 24 h urinary recovery with respect to the amount of (poly)phenols consumed was 6.2%. Our extensive description of the bioavailability of cranberry (poly)phenols lays important groundwork necessary to start understanding the fate of these compounds in humans.

Inhibition of herpes simplex type 1 and type 2 infections by Oximacro, a cranberry extract with a high content of A-type proanthocyanidins (PACs-A)

Posted: August 22, 2016
Authors: Terlizzi ME; Occhipinti A; Luganini A; Maffei ME; Gribaudo G.
Journal: Antiviral Research. 132 (pp 154-164),

Abstract: In the absence of efficient preventive vaccines, topical microbicides offer an attractive alternative in the prevention of Herpes simplex type 1 (HSV-1) and type 2 (HSV-2) infections. Because of their recognized anti-adhesive activity against bacterial pathogens, cranberry (Vaccinium macrocarpon Ait.) extracts may represent a natural source of new antiviral microbicides. However, few studies have addressed the applications of cranberry extract as a direct-acting antiviral agent. Here, we report on the ability of the novel cranberry extract Oximacro and its purified A-type proanthocyanidins (PACs-A), to inhibit HSV-1 and HSV-2 replication in vitro. Analysis of the mode of action revealed that Oximacro prevents adsorption of HSV-1 and HSV-2 to target cells. Further mechanistic studies confirmed that Oximacro and its PACs-A target the viral envelope glycoproteins gD and gB, thus resulting in the loss of infectivity of HSV particles. Moreover, Oximacro completely retained its anti-HSV activity even at acidic pHs (3.0 and 4.0) and in the presence of 10% human serum proteins; conditions that mimic the physiological properties of the vagina - a potential therapeutic location for Oximacro. Taken together, these findings indicate Oximacro as an attractive candidate for the development of novel microbicides of natural origin for the prevention of HSV infections.

Liquid chromatography with tandem mass spectrometry quantification of urinary proanthocyanin A2 dimer and its potential use as a biomarker of cranberry intake

Posted: August 22, 2016
Authors: Walsh J.M., Ren X., Zampariello C., Polasky D.A., McKay D.L., Blumberg J.B., Chen C.-Y.O.
Journal: Journal of Separation Science. 39 (2) (pp 342-349), 2016.

Abstract: The lack of a biomarker for the consumption of cranberries has confounded the interpretation of several studies investigating the effect of cranberry products, especially juices, on health outcomes. The objectives of this pilot study were to develop a liquid chromatography tandem mass spectrometric method for the quantification of the proanthocyanin dimer A-2 in human urine and validate urinary proanthocyanin dimer A-2 as a biomarker of cranberry intake. Five healthy, nonsmoking, premenopausal women (20-30 years of age, body mass index: 18.5-25 kg/m2) were assigned to consume a cranberry beverage containing 140 mg proanthocyanin and 35 kilocalories at 237 mL/day, according to a weekly dosing schedule for 7 weeks. Eleven 24 h and morning spot urine samples each were collected from each subject. A reliable, sensitive method for the detection of proanthocyanin dimer A-2 in urine using liquid chromatography with tandem mass spectrometry was developed with a limit of quantitation of 0.25 ng/mL and a relative standard deviation of 7.26%, precision of 5.7%, and accuracy of 91.7%. While proanthocyanin dimer A-2 was quantifiable in urine, it did not appear to be excreted in a concentration that corresponded to the dosing schedule and intake of cranberry juice.

NMR-based metabolomics reveals urinary metabolome modifications in female Sprague-Dawley rats by cranberry procyanidins.

Posted: August 22, 2016
Authors: Liu H., Tayyari F., Edison A.S., Su Z., Gu L.
Journal: Journal of Nutritional Biochemistry. 34 (pp 136-145), 2016

Abstract: A 1H NMR global metabolomics approach was used to investigate the urinary metabolome changes in female rats gavaged with partially purified cranberry procyanidins (PPCP) or partially purified apple procyanidins (PPAP). After collecting 24-h baseline urine, 24 female Sprague-Dawley rats were randomly separated into two groups and gavaged with PPCP or PPAP twice using a dose of 250 mg extracts per kilogram body weight. The 24-h urine samples were collected after the gavage. Urine samples were analyzed using 1H NMR. Multivariate analyses showed that the urinary metabolome in rats was modified after administering PPCP or PPAP compared to baseline urine metabolic profiles. 2D 1H-13C HSQC NMR was conducted to assist identification of discriminant metabolites. An increase of hippurate, lactate and succinate and a decrease of citrate and alpha-ketoglutarate were observed in rat urine after administering PPCP. Urinary levels of d-glucose, d-maltose, 3-(3'-hydroxyphenyl)-3-hydroxypropanoic acid, p-hydroxyphenylacetic acid, formate and phenol increased but citrate, alpha-ketoglutarate and creatinine decreased in rats after administering PPAP. Furthermore, the NMR analysis showed that the metabolome in the urine of rats administered with PPCP differed from those gavaged with PPAP. Compared to PPAP, PPCP caused an increase of urinary excretion of hippurate but a decrease of 3-(3'-hydroxyphenyl)-3-hydroxypropanoic acid, p-hydroxyphenylacetic acid and phenol. These metabolome changes caused by cranberry procyanidins may help to explain its reported health benefits and identify biomarkers of cranberry procyanidin intake.

Review of dried fruits: phytochemicals, antioxidant efficacies, and health benefits.

Posted: August 22, 2016
Authors: Chang SK, Alasalvar C, Shahidi F
Journal: Journal of Functional Foods; 2016. 21:113-132.

Abstract: Dried fruits, which serve as important healthful snacks worldwide, provide a concentrated form of fresh fruits. They are nutritionally equivalent to fresh fruits in smaller serving sizes, ranging from 30 to 43 g depending on the fruit, in current dietary recommendation in different countries. Daily consumption of dried fruits is recommended in order to gain full benefit of essential nutrients, health-promoting phytochemicals, and antioxidants that they contain, together with their desirable taste and aroma. Recently, much interest in the health benefits of dried fruits has led to many in vitro and in vivo (animal and human intervention) studies as well as the identification and quantification of various groups of phytochemicals. This review discusses phytochemical compositions, antioxidant efficacies, and potential health benefits of eight traditional dried fruits such as apples, apricots, dates, figs, peaches, pears, prunes, and raisins, together with dried cranberries. Novel product formulations and future perspectives of dried fruits are also discussed. Research findings from the existing literature published within the last 10 years have been compiled and summarised.

The efficacy of blueberry and grape seed extract combination on triple therapy for Helicobacter pylori eradication: a randomised controlled trial.

Posted: August 22, 2016
Authors: Chua CS; Yang KC; Chen JH; Liu YH; Hsu YH; Lee HC; Huang SY.
Journal: International Journal of Food Sciences and Nutrition; 2016. 67(2):177-183.

Abstract: Helicobacter pylori is a major risk factor for gastritis, gastric ulcers and gastric cancer. Traditional therapy with proton pump inhibitor and antibiotics is regarded as optimal for H. pylori eradication whereas, the eradication rate is unsatisfactory. Studies have reported that cranberry may inhibit H. pylori adhesion to the human gastric mucus but lack of other berry extracts have been evaluated in clinical study. Thus, a 9-week add-on randomised controlled trial was conducted to explore the impact of blueberry and grape seed extract (BGE) combinations traditional therapy for H. pylori eradication. In results, we found that there was no significant difference of eradication rate between the berry extract group and placebo group in the intention-to-treat analysis and in the per-protocol analysis (94.64% versus 84.62%, p=0.085). Diarrhoea, constipation and epigastric pain were observed increasing during ingestion of the berry extract in some cases. In conclusion, this study indicated that no significant difference existed between the BGE extract group and placebo group in eradication rate under triple therapy.

Impact of Cranberries on Gut Microbiota and Cardiometabolic Health: Proceedings of the Cranberry Health Research Conference 2015

Posted: August 3, 2016
Authors: Blumberg JB, Basu A, Krueger CG, Lila MA, Neto CC, Novotny JA, Reed JD, Rodriguez-Mateos A, Toner CD
Journal: Advances in Nutrition. 2016;7:759S-770S. doi: 10.3945/an.116.012583


Recent advances in cranberry research have expanded the evidence for the role of this Vaccinium berry fruit in modulating gut microbiota function and cardiometabolic risk factors. The A-type structure of cranberry proanthocyanidins seems to be responsible for much of this fruit’s efficacy as a natural antimicrobial. Cranberry proanthocyanidins interfere with colonization of the gut by extraintestinal pathogenic Escherichia coli in vitro and attenuate gut barrier dysfunction caused by dietary insults in vivo. Furthermore, new studies indicate synergy between these proanthocyanidins, other cranberry components such as isoprenoids and xyloglucans, and gut microbiota. Together, cranberry constituents and their bioactive catabolites have been found to contribute to mechanisms affecting bacterial adhesion, coaggregation, and biofilm formation that may underlie potential clinical benefits on gastrointestinal and urinary tract infections, as well as on systemic anti-inflammatory actions mediated via the gut microbiome. A limited but growing body of evidence from randomized clinical trials reveals favorable effects of cranberry consumption on measures of cardiometabolic health, including serum lipid profiles, blood pressure, endothelial function, glucoregulation, and a variety of biomarkers of inflammation and oxidative stress. These results warrant further research, particularly studies dedicated to the elucidation of dose-response relations, pharmacokinetic/metabolomics profiles, and relevant biomarkers of action with the use of fully characterized cranberry products. Freeze-dried whole cranberry powder and a matched placebo were recently made available to investigators to facilitate such work, including interlaboratory comparability.

Link to full text article: http://advances.nutrition.org/content/7/4/759S.full

Adherence Reduction of Campylobacter jejuni and Campylobacter coli Strains to HEp-2 Cells by Mannan Oligosaccharides and a High-Molecular-Weight Component of Cranberry Extract.

Posted: March 23, 2016
Authors: Ramirez-Hernandez A, Rupnow J, Hutkins RW
Journal: J Food Prot 78(8):1496-505

Abstract: Campylobacter infections are a leading cause of human bacterial gastroenteritis in the United States and are a major cause of diarrheal disease throughout the world. Colonization and subsequent infection and invasion of Campylobacter require that the bacteria adhere to the surface of host cells. Agents that inhibit adherence could be used prophylactically to reduce Campylobacter carriage and infection. Mannan oligosaccharides (MOS) have been used as a feed supplement in livestock animals to improve performance and to replace growth-promoting antibiotics. However, MOS and other nondigestible oligosaccharides may also prevent pathogen colonization by inhibiting adherence in the gastrointestinal tract. In addition, plant extracts, including those derived from cranberries, have been shown to have antiadherence activity against pathogens. The goal of this study was to assess the ability of MOS and cranberry fractions to serve as antiadherence agents against strains of Campylobacter jejuni and Campylobacter coli. Adherence experiments were performed using HEp-2 cells. Significant reductions in adherence of C. jejuni 29438, C. jejuni 700819, C. jejuni 3329, and C. coli 43485 were observed in the presence of MOS (up to 40 mg/ml) and with a high-molecular-weight fraction of cranberry extract (up to 3 mg/ml). However, none of the tested materials reduced adherence of C. coli BAA-1061. No additive effect in adherence inhibition was observed for an MOS-cranberry blend. These results suggest that both components, MOS and cranberry, could be used to reduce Campylobacter colonization and carriage in livestock animals and potentially limit human exposure to this pathogen.

Adhesion of Asaia Bogorensis to Glass and Polystyrene in the Presence of Cranberry Juice.

Posted: March 23, 2016
Authors: Antolak H, Kregiel D, Czyzowska A
Journal: J Food Prot 78(6):1186-90

Abstract: The aim of the study was to evaluate the adhesion abilities of the acetic acid bacterium Asaia bogorensis to glass and polystyrene in the presence of American cranberry (Vaccinium macrocarpon) juice. The strain of A. bogorensis used was isolated from spoiled commercial fruit-flavored drinking water. The cranberry juice was analyzed for polyphenols, organic acids, and carbohydrates using high-performance liquid chromatography and liquid chromatography-mass spectrometry techniques. The adhesive abilities of bacterial cells in culture medium supplemented with cranberry juice were determined using luminometry and microscopy. The viability of adhered and planktonic bacterial cells was determined by the plate count method, and the relative adhesion coefficient was calculated. This strain of A. bogorensis was characterized by strong adhesion properties that were dependent upon the type of surface. The highest level of cell adhesion was found on the polystyrene. However, in the presence of 10% cranberry juice, attachment of bacterial cells was three times lower. Chemical analysis of juice revealed the presence of sugars, organic acids, and anthocyanins, which were identified as galactosides, glucosides, and arabinosides of cyanidin and peonidin. A-type proanthocyanidins responsible for the antiadhesion properties of V. macrocarpon also were detected.

Antioxidant Activity and Polyphenol Content of Cranberries (Vaccinium Macrocarpon).

Posted: March 23, 2016
Authors: Kalin P, Gulcin I, Goren AC
Journal: Rec Nat Prod 9(4):496-502

Abstract: Cranberries (Vaccinium macrocarpon) contain many bioactive compounds and have some biological activities and beneficial health properties. In the study, antioxidant effects of lyophilized aqueous extract of cranberry (LAEC) and quantity of some its polyphenolic compounds were determined. For this purpose, we performed DPPH., DMPD.+, ABTS.+ and O2.- radicals scavenging activities, inhibition of lipid peroxidation activity by thiocyanate method, Cu2+ and Fe3+ reducing abilities, FRAP assay and Fe2+ binding activity. At the 10 micro g/mL concentration, LAEC inhibited 52.4% lipid peroxidation produced by linoleic acid emulsion. Also, alpha -tocopherol, BHA, trolox, and BHT had 52.5, 89.9, 93.1 and 94.9% inhibition value at 30 micro g/mL concentration, respectively. Quantitative amounts of some phenolic compounds in LAEC were investigated by high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). p-Hydroxy benzoic acid was found as the most abundant phenolic compound (55 mg/kg extract) in LAEC.

Bioactive Compounds and Antioxidant Activity in Different Types of Berries.

Posted: March 23, 2016
Authors: Skrovankova S, Sumczynski D, Mlcek J, Jurikova T, Sochor J
Journal: Int J Mol Sci 16(10):24673-706

Abstract: Berries, especially members of several families, such as Rosaceae (strawberry, raspberry, blackberry), and Ericaceae (blueberry, cranberry), belong to the best dietary sources of bioactive compounds (BAC). They have delicious taste and flavor, have economic importance, and because of the antioxidant properties of BAC, they are of great interest also for nutritionists and food technologists due to the opportunity to use BAC as functional foods ingredients. The bioactive compounds in berries contain mainly phenolic compounds (phenolic acids, flavonoids, such as anthocyanins and flavonols, and tannins) and ascorbic acid. These compounds, either individually or combined, are responsible for various health benefits of berries, such as prevention of inflammation disorders, cardiovascular diseases, or protective effects to lower the risk of various cancers. In this review bioactive compounds of commonly consumed berries are described, as well as the factors influencing their antioxidant capacity and their health benefits.

Cranberry Anthocyanin Extract Prolongs Lifespan of Fruit Flies

Posted: March 23, 2016
Authors: Wang L, Li YM, Lei L, Liu Y, Wang X, Ma KY, Chen ZY
Journal: Exp Gerontol 69:189-95

Abstract: Cranberry is an excellent source of dietary antioxidants. The present study investigated the effect of cranberry anthocyanin (CrA) extract on the lifespan of fruit flies with focus on its interaction with aging-related genes including superoxide dismutase (SOD), catalase (CAT), methuselah (MTH), insulin receptor (InR), target of rapamycin (TOR), hemipterus (Hep), and phosphoenolpyruvate carboxykinase (PEPCK). Results showed that diet containing 20mg/mL CrA could significantly prolong the mean lifespan of fruit flies by 10% compared with the control diet. This was accompanied by up-regulation of SOD1 and down-regulation of MTH, InR, TOR and PEPCK. The stress resistance test demonstrated that CrA could reduce the mortality rate induced by H2O2 but not by paraquat. It was therefore concluded that the lifespan-prolonging activity of CrA was most likely mediated by modulating the genes of SOD1, MTH, InR, TOR and PEPCK.

Cranberry Extract-Enriched Diets Increase NAD(P)H:quinone Oxidoreductase and Catalase Activities in Obese but not in Nonobese Mice

Posted: March 23, 2016
Authors: Bousova I, Bartikova H, Matouskova P, Lnenickova K, Zappe L, Valentova K, Szotakova B, Martin J, Skalova L
Journal: Nutr Res 35(10):901-9

Abstract: Consumption of antioxidant-enriched diets is 1 method of addressing obesity, which is associated with chronic oxidative stress and changes in the activity/expression of various enzymes. In this study, we hypothesized that the modulation of antioxidant enzymes and redox status through a cranberry extract (CBE)-enriched diet would differ between obese and nonobese mice. The CBE used in this study was obtained from the American cranberry (Vaccinium macrocarpon, Ericaceae), a popular constituent of dietary supplements that is a particularly rich source of (poly)phenols and has strong antioxidant properties. The present study was designed to test and compare the in vivo effects of 28-day consumption of a CBE-enriched diet (2%) on the antioxidant status of nonobese mice and mice with monosodium glutamate-induced obesity. Plasma, erythrocytes, liver, and small intestine were studied concurrently to obtain more complex information. The specific activities, protein, and messenger RNA expression levels of antioxidant enzymes as well as the levels of malondialdehyde and thiol (SH) groups were analyzed. Cranberry extract treatment increased the SH group content in plasma and the glutathione S-transferase activity in the erythrocytes of the obese and nonobese mice. In addition, in the obese animals, the CBE treatment reduced the malondialdehyde content in erythrocytes and increased
NAD(P)H: quinone oxidoreductase (liver) and catalase (erythrocytes and small intestine) activities. The elevation of hepatic
NAD(P)H: quinone oxidoreductase activity was accompanied by an increase in the corresponding messenger RNA levels. The effects of CBE on the activity of antioxidant enzymes and redox status were more pronounced in the obese mice compared with the nonobese mice.

Cranberry Flavonoids Modulate Cariogenic Properties of Mixed-Species Biofilm through Exopolysaccharides-Matrix Disruption

Posted: March 23, 2016
Authors: Kim D, Hwang G, Liu Y, Wang Y, Singh AP, Vorsa N, Koo H
Journal: PLoS ONE 10(12):e0145844

Abstract: The exopolysaccharides (EPS) produced by Streptococcus mutans-derived glucosyltransferases (Gtfs) are essential virulence factors associated with the initiation of cariogenic biofilms. EPS forms the core of the biofilm matrix-scaffold, providing mechanical stability while facilitating the creation of localized acidic microenvironments. Cranberry flavonoids, such as A-type proanthocyanidins (PACs) and myricetin, have been shown to inhibit the activity of Gtfs and EPS-mediated bacterial adhesion without killing the organisms. Here, we investigated whether a combination of cranberry flavonoids disrupts EPS accumulation and S. mutans survival using a mixed-species biofilm model under cariogenic conditions. We also assessed the impact of cranberry flavonoids on mechanical stability and the in situ pH at the biofilm-apatite interface. Topical application of an optimized combination of PACs oligomers (100-300 muM) with myricetin (2 mM) twice daily was used to simulate treatment regimen experienced clinically. Treatments with cranberry flavonoids effectively reduced the insoluble EPS content (>80% reduction vs. vehicle-control; p<0.001), while hindering S. mutans outgrowth within mixed-species biofilms. As a result, the 3D architecture of cranberry-treated biofilms was severely compromised, showing a defective EPS-matrix and failure to develop microcolonies on the saliva-coated hydroxyapatite (sHA) surface. Furthermore, topical applications of cranberry flavonoids significantly weaken the mechanical stability of the biofilms; nearly 90% of the biofilm was removed from sHA surface after exposure to a shear stress of 0.449 N/m2 (vs. 36% removal in vehicle-treated biofilms). Importantly, in situ pH measurements in cranberry-treated biofilms showed significantly higher pH values (5.2 +/- 0.1) at the biofilm-apatite interface vs. vehicle-treated biofilms (4.6 +/- 0.1). Altogether, the data provide important insights on how cranberry flavonoids treatments modulate virulence properties by disrupting the biochemical and ecological changes associated with cariogenic biofilm development, which could lead to new alternative or adjunctive antibiofilm/anticaries chemotherapeutic formulations.

Effect of Dried Powder Preparation Process on Polyphenolic Content and Antioxidant Capacity of Cranberry (Vaccinium macrocarpon L.).

Posted: March 23, 2016
Authors: Oszmianski J, Kolniak-Ostek J, Lachowicz S, Gorzelany J, Matlok N
Journal: Ind Crop Prod 77:658-665.

Abstract: The aim of the study was to evaluate the effect of the degree of fragmentation of cranberry fruit (Vaccinium macrocarpon L.) on the chemical composition and antioxidant activity of fruit powders and lyophilized pomace and juices. In analyzed samples, the basic chemical composition, total polyphenolics and antioxidant capacity were determined. Thirty-nine polyphenolic compounds, including 9 phenolic acids, 7 anthocyanins, 9 flavan-3-ols and 14 flavonols, were identified. Polyphenolic concentrations in pomaces ranged from 16 038.74 mg/100 g DW in samples from whole fruits to 17 802.52 mg/100 g DW in samples from crushed fruits. In juices, phenolic concentrations ranged from 873.12 mg/100 g DW in products from whole fruits to 3177.87 mg/100 g DW in products from crushed fruits. Antioxidant capacities were higher in dry products than in juices. The highest DPPH, ABTS and FRAP values were determined in dry pomaces obtained from crushed fruits (156.94, 275.22 and 71.47 micro mol/g DW, respectively).

Modulatory Effects of a Cranberry Extract Co-Supplementation with Bacillus Subtilis CU1 Probiotic on Phenolic Compounds Bioavailability and Gut Microbiota Composition in High-Fat Diet-Fed Mice.

Posted: March 23, 2016
Authors: Dudonne S, Varin TV, Forato Anhe F, Dube P, Roy D, Pilon G, Marette A, Levy E, Jacquot C, Urdaci M, Desjardins Y
Journal: PharmaNutrition [doi: 10.1016/j.phanu.2015.04.002]

Abstract: Cranberry consumption has been demonstrated to improve features of the metabolic syndrome, therefore providing an alternative strategy to prevent obesity and type-2 diabetes. Moreover, gut dysbiosis is now considered as a key factor in metabolic disorders. In order to understand the involvement of phenolic compounds in the health-improving effects of cranberry, this study aimed to investigate their bioavailability after oral administration of a cranberry extract (CE) to high-fat high-sucrose (HFHS) fed mice, and to explore a possible modulation of gut microbiota composition following a co-supplementation with spores of Bacillus subtilis CU1 probiotic (CE/P). Phenolic metabolites were extracted and characterized from plasma using &#956;SPE-UHPLC-MS/MS, and a metagenomic analysis was performed on feces to assess gut bacterial composition. 22 circulating metabolites were identified, mainly microbial degradation products of native cranberry phenolic compounds. Plasma concentration of 3 microbial metabolites was significantly increased with the CE/P co-treatment: p-coumaric acid, m-coumaric acid and p-hydroxybenzoic acid (+53%, +103% and +70%, respectively). Associated to this modulation, we reported significant differences in the proportion of Barnesiella and Oscillibacter genera in CE/P treated mice in comparison with control animals. This study thus highlights the impact of an altered gut microbiota on phenolic compounds degradation and bioavailability in mice.

Nano-Liquid Chromatography Coupled to Time-of-Flight Mass Spectrometry for Phenolic Profiling: a Case Study in Cranberry Syrups

Posted: March 23, 2016
Authors: Contreras Mdel M, Arraez-Roman D, Fernandez-Gutierrez A, Segura-Carretero A
Journal: Talanta 132:929-38

Abstract: A new method based on nano-liquid chromatography coupled to time-of-flight mass spectrometry (nano-LC-TOF-MS) using lock-mass calibration was developed to facilitate the accurate and routine characterization and quantification of phenolic compounds. Thus, it was applied to study cranberry syrups, in which, using negative ionization mode, a total of nine phenolic compounds were unequivocally identified using standards and 38 tentatively taking into account their retention time, accurate mass (errors<5 ppm) data and isotope pattern, as well as literature. Among them, 13 compounds, belonging to flavonols and iridoids conjugated with phenolic acids, were reported for first time in cranberry or cranberry based-products. The analytical method was also validated using chlorogenic acid, p-coumaric acid, (+)-catechin, (-)-epicatechin, procyanidin A2, quercetin 3-O-glucoside, quercetin 3-O-rhamnoside, quercetin, and myricetin standards. In this way, the analytical method showed adequate linearity, with R(2) above 0.99, and acceptable values of intra- and inter-day repeatability of the retention time and peak area. The detection limits and quantification were between 1.0-15.6 ng mL(-1) and 2.0-62.5 ng mL(-1), respectively. The method can be extended to characterize phenolic compounds in other food and plant matrices, and as well biological samples.

Potential Oral Health Benefits of Cranberry

Posted: March 23, 2016
Authors: Bodet C, Grenier D, Chandad F, Ofek I, Steinberg D, Weiss EI.
Journal: Crit Rev Food Sci Nutr 48(7):672-80

Abstract: In the past decade, cranberry extracts have been attracting ever-growing attention by dental researchers. The potential benefits of cranberry components in reducing oral diseases, including dental caries and periodontitis, are discussed in this review. A non-dialysable cranberry fraction enriched in high molecular weight polyphenols has very promising properties with respect to cariogenic and periodontopathogenic bacteria, as well as to the host inflammatory response and enzymes that degrade the extracellular matrix. Cranberry components are potential anti-caries agents since they inhibit acid production, attachment, and biofilm formation by Streptococcus mutans. Glucan-binding proteins, extracellular enzymes, carbohydrate production, and bacterial hydrophobicity, are all affected by cranberry components. Regarding periodontal diseases, the same cranberry fraction inhibits host inflammatory responses, production, and activity of enzymes that cause the destruction of the extracellular matrix, biofilm formation, and adherence of Porphyromonas gingivalis, and proteolytic activities and coaggregation of periodontopathogens. The above-listed effects suggest that cranberry components, especially those with high molecular weight, could serve as bioactive molecules for the prevention and/or treatment of oral diseases.

Profiling the Metabolome Changes Caused by Cranberry Procyanidins in Plasma of Female Rats Using (1) H NMR and UHPLC-Q-Orbitrap-HRMS Global Metabolomics Approaches

Posted: March 23, 2016
Authors: Liu H, Garrett TJ, Tayyari F, Gu L
Journal: Mol Nutr Food Res 59(11):2107-18

Abstract: SCOPE: The objective was to investigate the metabolome changes in female rats gavaged with partially purified cranberry procyanidins (PPCP) using (1) H NMR and UHPLC-Q-Orbitrap-HRMS metabolomics approaches, and to identify the contributing metabolites.
METHODS AND RESULTS: Twenty-four female Sprague-Dawley rats were randomly separated into two groups and administered PPCP or partially purified apple procyanidins (PPAP) for three times using a 250 mg extracts/kg body weight dose. Plasma was collected 6 h after the last gavage and analyzed using (1) H NMR and UHPLC-Q-Orbitrap-HRMS. No metabolome difference was observed using (1) H NMR metabolomics approach. However, LC-HRMS metabolomics data show that metabolome in the plasma of female rats administered PPCP differed from those gavaged with PPAP. Eleven metabolites were tentatively identified from a total of 36 discriminant metabolic features based on accurate masses and/or product ion spectra. PPCP caused a greater increase of exogenous metabolites including p-hydroxybenzoic acid, phenol, phenol-sulphate, catechol sulphate, 3, 4-dihydroxyphenylvaleric acid, and 4'-O-methyl-(-)-epicatechin-3'-O-beta-glucuronide in rat plasma. Furthermore, the plasma level of O-methyl-(-)-epicatechin-O-glucuronide, 4-hydroxy-5-(hydroxyphenyl)-valeric acid-O-sulphate, 5-(hydroxyphenyl)-Y-valerolactone-O-sulphate, 4-hydroxydiphenylamine, and peonidin-3-O-hexose were higher in female rats administered with PPAP.
CONCLUSION: The metabolome changes caused by cranberry procyanidins were revealed using an UHPLC-Q-Orbitrap-HRMS global metabolomics approach. Exogenous and microbial metabolites were the major identified discriminate biomarkers.

A review and critical analysis of the scientific literature related to 100% fruit juice and human health

Posted: September 30, 2015
Authors: Hyson DA
Journal: Adv Nutr 6(1):37-51

Abstract: The association between the consumption of pure (100%) fruit juice (PFJ) and human health is uncertain. The current review summarizes data published between 1995 and 2012 related to PFJ with a focus on juices that are widely available and studied in forms representing native juice without supplemental nutrients or enhanced phytochemical content. The effects of apple, cranberry, grape, grapefruit, orange, and pomegranate PFJ intake on outcomes linked to cancer, cardiovascular disease, cognition, hypertension, inflammation, oxidation, platelet function, urinary tract infection, and vascular reactivity are reviewed. Implications for bodyweight regulation are also addressed. The collective data are provocative although challenges and unanswered questions remain. There are many plausible mechanisms by which PFJ might be protective, and investigation of its effects on human health and disease prevention must remain an active area of research

Characterization and comparison of phenolic composition, antioxidant capacity and instrumental taste profile of juices from different botanical origins

Posted: September 28, 2015
Authors: Granato D, Karnopp AR, van Ruth SM
Journal: J Sci Food Agric 95(10):1997-2006

Abstract: BACKGROUND: The European Union registered a consumption of about 10.7 billion litres of juices in 2011 and a great part of this amount is imported from other countries, which makes the monitoring of their quality essential. This work was aimed at mapping the quality of various juices from different botanical origins from instrumental taste, chemical marker and antioxidant capacity perspectives. It also characterized the individual phenolic composition of juices previously classified according to their antioxidant activity and total phenolic material level.
RESULTS: Overall, by using correlation analysis and chemometrics (HCA and PCA), data showed that total phenolics, specifically gallic acid, p-coumaric acid, anthocyanins, flavanols and flavonols, are the main contributors to the antioxidant activity. Elderberry and pomegranate juices presented the highest phenolic content and antioxidant activity. On the other hand, orange, apple and cranberry juices had the lowest levels of total phenolics and flavonoids, DPPH and CUPRAC.
CONCLUSION: The use of chemometrics coupled to ANOVA seems to be a suitable approach to evaluate the quality of fruit juices from different botanical origins. Additionally, the instrumental taste profile correlated well with the chemical composition and antioxidant capacity, showing its potential application in assessing the functionality of juices.

Chemical characterization and chemo-protective activity of cranberry phenolic powders in a model cell culture. Response of the antioxidant defenses and regulation of signaling pathways

Posted: September 28, 2015
Journal: Food Res Int 71:68-82

Abstract: Oxidative stress and reactive oxygen species (ROS)-mediated cell damage are implicated in various chronic pathologies. Emerging studies show that polyphenols may act by increasing endogenous antioxidant defense potential. Cranberry has one of the highest polyphenol content among commonly consumed fruits. In this study, the hepato-protective activity of a cranberry juice (CJ) and cranberry extract (CE) powders against oxidative stress was screened using HepG2 cells, looking at ROS production, intracellular non-enzymatic and enzymatic antioxidant defenses by reduced glutathione concentration (GSH), glutathione peroxidase (GPx) and glutathione reductase (GR) activity and lipid peroxidation biomarker malondialdehyde (MDA). Involvement of major protein kinase signaling pathways was also evaluated. Both powders in basal conditions did not affect cell viability but decreased ROS production and increased GPx activity, conditions that may place the cells in favorable conditions against oxidative stress. Powder pre-treatment of HepG2 cells for 20 h significantly reduced cell damage induced by 400 micro M tert-butylhydroperoxide (t-BOOH) for 2 h. Both powders (5-50 micro g/ml) reduced t-BOOH-induced increase of MDA by 20% (CJ) and 25% (CE), and significantly reduced over-activated GPx and GR. CE, with a significantly higher amount of polyphenols than CJ, prevented a reduction in GSH and significantly reduced ROS production. CJ reversed the t-BOOH-induced increase in phospho-c-Jun N-terminal kinase. This study demonstrates that cranberry polyphenols may help protect liver cells against oxidative insult by modulating GSH concentration, ROS and MDA generation, antioxidant enzyme activity and cell signaling pathways.

Comparative assessment of Cranberry and Chlorhexidine mouthwash on streptococcal colonization among dental students: A randomized parallel clinical trial.

Posted: September 28, 2015
Authors: Khairnar MR, Karibasappa GN, Dodamani AS, Vishwakarma P, Naik RG, Deshmukh MA
Journal: Contemp Clin Dent 6(1):35-9

Abstract: BACKGROUND: Chlorhexidine gluconate mouthwash has earned an eponym of the gold standard against oral infections, but with certain limitations. There is no effective alternative to Chlorhexidine. Cranberry is known to inhibit bacterial adhesion in various systemic infections and acts as a strong antioxidant. However, it is less explored for its dental use. Hence, there is a need to evaluate its effect against oral infections.
AIM: The aim was to compare the efficacy of 0.2% Chlorhexidine mouthwash with 0.6% Cranberry mouthwash on Streptococcus mutans.
MATERIALS AND METHODS: This was a double-blind, randomized parallel group clinical trial. Total sample of 50 subjects, aged 18-20 years, were randomly divided into two groups, Group A (25) and Group B (25) were given 10 mL of Chlorhexidine mouthwash and Cranberry mouthwash twice daily, respectively, for 14 days each. The plaque samples, which were taken from the subjects on 1(st) day and 14(th) day, were inoculated on blood agar plates and incubated at 37degreeC for 24-48 h. Number of streptococcal colony forming units were calculated using digital colony counter. The data were subjected to paired t-test and unpaired t-test at a 5% significance level.
RESULTS: (1) Chlorhexidine mouthwash showed 69% reduction whereas Cranberry mouthwash showed 68% reduction in S. mutans count. (2) No significant difference was seen between Chlorhexidine and Cranberry mouthwash on streptococci.
CONCLUSION: Cranberry mouthwash is equally effective as Chlorhexidine mouthwash with beneficial local and systemic effect. Hence, it can be used effectively as an alternative to Chlorhexidine mouthwash.

Cranberries (Oxycoccus quadripetalus) inhibit lipid metabolism and modulate leptin and adiponectin secretion in 3T3-L1 adipocytes

Posted: September 28, 2015
Authors: Kowalska K, Olejnik A, Rychlik J, Grajek W
Journal: Food Chem 185:383-8

Abstract: It has previously been shown that lyophilized cranberries (LCB) decreased lipid accumulation in 3T3-L1 cells and inhibited preadipocyte differentiation by down-regulation of the expression of key transcription factors (PPARgamma, C/EBPalpha, SREBP1) of the adipogenesis pathway. To elucidate the molecular basis of anti-lipogenic activity of LCB, the expression of several genes involved in lipid metabolism, such as adipocyte fatty acid-binding protein (aP2), lipoprotein lipase (LPL), fatty acid synthase (FAS), hormone sensitive lipase (HSL) and perilipin 1 (PLIN1), was examined in the present study. Additionally, the effects of LCB on adiponectin and leptin expression and protein secretion were also investigated. LCB reduced lipid accumulation during preadipocyte differentiation by down-regulation of the mRNA level of aP2, FAS, LPL, HSL and PLIN1. Moreover, LCB decreased leptin gene expression and increased adiponectin gene expression and protein secretion in a dose-dependent manner. Therefore cranberries could be considered as bioactive factors, which are effective in the inhibition of adipose tissue mass production.

Depolymerisation optimisation of cranberry procyanidins and transport of resultant oligomers on monolayers of human intestinal epithelial Caco-2 cells

Posted: September 28, 2015
Authors: Ou K, Gu L
Journal: Food Chem 167:45-51

Abstract: Procyanidins in cranberries are predominantly polymers (>85%). The objective of this study was to optimise the depolymerisation of polymers and to investigate the absorption of resultant oligomers on Caco-2 cell monolayers. Depolymerisation conditions were optimised using response surface methodology. Depolymerisation, with or without added epicatechin, yielded 644 mug and 202 mug of oligomers (monomer through tetramers) per mg of partially purified polymers (PP), respectively. Oligomers (yielded from both methods) were transported through Caco-2 cell monolayer despite absorption rates being low. With the aid of response surface methodology, the optimum depolymerisation conditions were determined to be 60degreeC, 0.1M HCl in methanol and 3h without added epicatechin. The predicted maximum yield was 364 mug oligomers per mg of PP. The optimum depolymerisation condition with added epicatechin shared the same temperature, acid concentration and reaction time, in addition to an epicatechin/PP mass ratio of 2.19. Its predicted maximum oligomer yield was 1,089 mug/mg. The predicted yields were verified by experimental data.

Effect of high-molecular-weight component of Cranberry on plaque and salivary Streptococcus mutans counts in children: an in vivo study.

Posted: September 28, 2015
Authors: Gupta A, Bansal K, Marwaha M
Journal: J Indian Soc Pedod Prev Dent 33(2):128-33

Abstract: BACKGROUND: Previous investigations showed that a high-molecular-weight, nondialyzable material (NDM) from cranberries inhibits the adhesion of a number of bacterial species and prevents the coaggregation of many oral bacterial pairs.
AIM: In the present study, the effect of mouthrinse containing high-molecular-weight component of cranberry was evaluated on colonization of Streptococcus mutans in children and compared it with a control mouthrinse without high-molecular-weight component on Streptococcus mutans counts.
MATERIALS AND METHODS: A high-molecular-weight NDM was isolated from cranberry juice concentrate after the dialysis of the cranberry concentrate; followed by lyophilization. A mouthwash was prepared especially for the study having NDM in the concentration of 3 mg/ml. Following 4 weeks of daily usage of cranberry-containing mouthwash by the children of an experimental group (n = 20), the Streptococcus mutans counts in plaque and saliva were compared with that in control group using placebo mouthwash (n = 20) with the help of Dentocult SM strips.
RESULTS: There was a highlysignificant reduction in Streptococcus mutans counts in saliva and plaque of children using mouthwash containing cranberry NDM (P < 0.05) compared to control.
CONCLUSION: The data suggest that the high-molecular-weight cranberry extract in mouthwash has a significant potential in reducing the Streptococcus counts in the oral environment.

Green tea polyphenol epigallocatechin-3-gallate and cranberry proanthocyanidins act in synergy with cathelicidin (LL-37) to reduce the LPS-induced inflammatory response in a three-dimensional co-culture model of gingival epithelial cells and fibroblasts.

Posted: September 28, 2015
Authors: Lombardo Bedran TB, Palomari Spolidorio D, Grenier D
Journal: Arch Oral Biol 60(6):845-53

Abstract: OBJECTIVES: The human antimicrobial peptide cathelicidin (LL-37) possesses anti-inflammatory properties that may contribute to attenuating the inflammatory process associated with chronic periodontitis. Plant polyphenols, including those from cranberry and green tea, have been reported to reduce inflammatory cytokine secretion by host cells. In the present study, we hypothesized that A-type cranberry proanthocyanidins (AC-PACs) and green tea epigallocatechin-3-gallate (EGCG) act in synergy with LL-37 to reduce the secretion of inflammatory mediators by oral mucosal cells.
METHODS: A three-dimensional (3D) co-culture model of gingival epithelial cells and fibroblasts treated with non-cytotoxic concentrations of AC-PACs (25 and 50 mug/ml), EGCG (1 and 5 mug/ml), and LL-37 (0.1 and 0.2 muM) individually and in combination (AC-PACs+LL-37 and EGCG+LL-37) were stimulated with Aggregatibacter actinomycetemcomitans lipopolysaccharide (LPS). Multiplex ELISA assays were used to quantify the secretion of 54 host factors, including chemokines, cytokines, growth factors, matrix metalloproteinases (MMPs), and tissue inhibitors of metalloproteinases (TIMPs).
RESULTS: LL-37, AC-PACs, and EGCG, individually or in combination, had no effect on the regulation of MMP and TIMP secretion but inhibited the secretion of several cytokines. AC-PACs and LL-37 acted in synergy to reduce the secretion of CXC-chemokine ligand 1 (GRO-alpha), granulocyte colony-stimulating factor (G-CSF), and interleukin-6 (IL-6), and had an additive effect on reducing the secretion of interleukin-8 (IL-8), interferon-gamma inducible protein 10 (IP-10), and monocyte chemoattractant protein-1 (MCP-1) in response to LPS stimulation. EGCG and LL-37 acted in synergy to reduce the secretion of GRO-alpha, G-CSF, IL-6, IL-8, and IP-10, and had an additive effect on MCP-1 secretion.
CONCLUSION: The combination of LL-37 and natural polyphenols from cranberry and green tea acted in synergy to reduce the secretion of several cytokines by an LPS-stimulated 3D co-culture model of oral mucosal cells. Such combinations show promising results as potential adjunctive therapies for treating inflammatory periodontitis.Copyright © 2015 Elsevier Ltd. All rights reserved.

Methods to determine effects of cranberry proanthocyanidins on extraintestinal infections: Relevance for urinary tract health.

Posted: September 28, 2015
Authors: Feliciano RP, Krueger CG, Reed JD
Journal: Mol Nutr Food Res 59(7):1292-306,

Abstract: Urinary tract infections (UTI) are one of the most frequent extraintestinal infections caused by Escherichia coli (ExPEC). Cranberry juice has been used for decades to alleviate symptoms and prevent recurrent UTI. The putative compounds in cranberries are proanthocyanidins (PAC), specifically PAC with "A-type" bonds. Since PAC are not absorbed, their health benefits in UTI may occur through interactions at the mucosal surface in the gastrointestinal tract. Recent research showed that higher agglutination of ExPEC and reduced bacterial invasion are correlated with higher number of "A-type" bonds and higher degree of polymerization of PAC. An understanding of PAC structure-activity relationship is becoming feasible due to advancements, not only in obtaining purified PAC fractions that allow accurate estimation, but also in high-resolution MS methodologies, specifically, MALDI-TOF MS. A recent MALDI-TOF MS deconvolution method allows quantification of the ratios of "A-type" to "B-type" bonds enabling characteristic fingerprints. Moreover, the generation of fluorescently labeled PAC allows visualization of the interaction between ExPEC and PAC with microscopy. These tools can be used to establish structure-activity relationships between PAC and UTI and give insight on the mechanism of action of these compounds in the gut without being absorbed.

Phenol antioxidant quantity and quality in foods: fruits

Posted: September 28, 2015
Authors: Vinson JA, Su X, Zubik L, Bose P
Journal: J Agric Food Chem 49(11):5315-21

Abstract: The free and bound phenols have been measured in 20 fruits commonly consumed in the American diet. Phenols were measured colorimetrically using the Folin-Ciocalteu reagent with catechin as the standard after correction for ascorbic acid contribution. On a fresh weight basis, cranberry had the highest total phenols, and was distantly followed by red grape. Free and total phenol quality in the fruits was analyzed by using the inhibition of lower density lipoprotein oxidation promoted by cupric ion. Ascorbate had only a minor contribution to the antioxidants in fruits with the exception of melon, nectarine, orange, white grape, and strawberry. The fruit extracts' antioxidant quality was better than the vitamin antioxidants and most pure phenols, suggesting synergism among the antioxidants in the mixture. Using our assay, fruits had significantly better quantity and quality of phenol antioxidants than vegetables. Fruits, specifically apples and cranberries, have phenol antioxidants that can enrich lower density lipoproteins and protect them from oxidation. The average per capita consumption of fruit phenols in the U.S. is estimated to be 255 mg/day of catechin equivalents.

Prevention of oxidative stress, inflammation and mitochondrial dysfunction in the intestine by different cranberry phenolic fractions

Posted: September 28, 2015
Authors: Denis MC, Desjardins Y, Furtos A, Marcil V, Dudonne S, Montoudis A, Garofalo C, Delvin E, Marette A, Levy E
Journal: Clinical Science 128(3):197-212

Abstract: Cranberry fruit has been reported to have high antioxidant effectiveness that is potentially linked to its richness in diversified polyphenolic content. The aim of the present study was to determine the role of cranberry polyphenolic fractions in oxidative stress (OxS), inflammation and mitochondrial functions using intestinal Caco-2/15 cells. The combination of HPLC and UltraPerformance LC-tandem quadrupole (UPLC-TQD) techniques allowed us to characterize the profile of low, medium and high molecular mass polyphenolic compounds in cranberry extracts. The medium molecular mass fraction was enriched with flavonoids and procyanidin dimers whereas procyanidin oligomers (DP > 4) were the dominant class of polyphenols in the high molecular mass fraction. Pre-incubation of Caco-2/15 cells with these cranberry extracts prevented iron/ascorbate-mediated lipid peroxidation and counteracted lipopolysaccharide-mediated inflammation as evidenced by the decrease in pro-inflammatory cytokines (TNF-alpha and interleukin-6), cyclo-oxygenase-2 and prostaglandin E2. Cranberry polyphenols (CP) fractions limited both nuclear factor kappaB activation and Nrf2 down-regulation. Consistently, cranberry procyanidins alleviated OxS-dependent mitochondrial dysfunctions as shown by the rise in ATP production and the up-regulation of Bcl-2, as well as the decline of protein expression of cytochrome c and apoptotic-inducing factor. These mitochondrial effects were associated with a significant stimulation of peroxisome-proliferator-activated receptor gamma co-activator-1-alpha, a central inducing factor of mitochondrial biogenesis and transcriptional co-activator of numerous downstream mediators. Finally, cranberry procyanidins forestalled the effect of iron/ascorbate on the protein expression of mitochondrial transcription factors (mtTFA, mtTFB1, mtTFB2). Our findings provide evidence for the capacity of CP to reduce intestinal OxS and inflammation while improving mitochondrial dysfunction.

Cranberry extract standardized for proanthocyanidins promotes the immune response of Caenorhabditis elegans to Vibrio cholerae through the p38 MAPK pathway and HSF-1.

Posted: April 1, 2015
Authors: Dinh J, Angeloni JT, Pederson DB, Wang X, Cao M, Dong Y
Journal: PLoS One 9(7):e103290.

Abstract: Botanicals are rich in bioactive compounds, and some offer numerous beneficial effects to animal and human health when consumed. It is well known that phytochemicals in cranberries have anti-oxidative and antimicrobial activities. Recently, an increasing body of evidence has demonstrated that cranberry
phytochemicals may have potential benefits that promote healthy aging. Here, we use Caenorhabditis elegans as a model to show that water-soluble cranberry extract standardized to 4.0% proanthocyanidins (WCESP), a major component of
cranberries, can enhance host innate immunity to resist against Vibrio cholerae (V. cholerae; wild type C6706 (O1 El Tor biotype)) infection. Supplementation of WCESP did not significantly alter the intestinal colonization of V. cholerae, but
upregulated the expression of C. elegans innate immune genes, such as clec-46, clec-71, fmo-2, pqn-5 and C23G10.1. Additionally, WCESP treatment did not affect the growth of V. cholerae and expression of the major bacterial virulence genes, and only slightly reduced bacterial colonization within C. elegans intestine. These findings indicate that the major components of WCESP, including proanthocyanidins (PACs), may play an important role in enhancing the host innate
immunity. Moreover, we engaged C. elegans mutants and identified that the p38 MAPK signaling, insulin/IGF-1 signaling (IIS), and HSF-1 play pivotal roles in the WCESP-mediated host immune response. Considering the level of conservation between the innate immune pathways of C. elegans and humans, the results of this study suggest that WCESP may also play an immunity-promoting role in higher order organisms.

Gut-targeted immunonutrition boosting natural killer cell activity using Saccharomyces boulardii lysates in immuno-compromised healthy elderly subjects.

Posted: April 1, 2015
Authors: Naito Y, Marotta F, Kantah MK, Zerbinati N, Kushugulova A, Zhumadilov Z, Illuzzi N, Sapienza C, Takadanohara H, Kobayashi R, Catanzaro R.
Journal: Rejuvenation Res 17(2):184-7.

Abstract: The aim of this study was to assess the immunomodulatory effect of KC-1317 (a symbiotic mixture containing Saccharomyces boulardii lysate in a cranberry, colostrum-derived lactoferrin, fragaria, and lactose mixture) supplementation in immune-compromised but otherwise healthy elderly subjects. A liquid formulation of KC-1317 was administered in a randomized controlled trial (RCT) fashion to
healthy volunteers (65-79 years) previously selected for low natural killer (NK) cell activity, and this parameter was checked at the completion of the study. A significant improvement in NK cell activity of KC-1317 consumers was observed as
compared to placebo at the end of 2 months. Although preliminary, these beneficial immune-modulatory effects of KC-1317 in aged individuals might indicate its employment within a wider age-management strategy.

Analysis of A-type and B-type highly polymeric proanthocyanidins and their biological activities as nutraceuticals.

Posted: July 25, 2014
Authors: Yokota K, Kimura H, Ogawa S, Akihiro T
Journal: J Chem DOI: 10.1155/2013/352042

Abstract: Proanthocyanidins have a series of heteroflavan-3-ols, (+)-catechin/(-)-epicatechin units, which are linked through a single B-type linkage and a doubly linked A-type linkage. Recently, we have performed the structural characterization of seed shells of the Japanese horse chestnut and fruits of blueberry and cranberry. The molecular sizes of them were higher in the order of blueberry > cranberry > seed shells of the Japanese horse chestnut between the respective fractions. For the analysis of terminal and extension units in those proanthocyanidins, the isolated fractions were subjected to the thiolytic cleavage of the B-type linkages using 1-dodecanethiol, and the resulting degradation products were identified by ultraperformance liquid chromatography coupled with electrospray-ionization mass spectrometry. These analyses provided fast and good resolution of the degradation products and revealed higher proportions of A-type linkages compared with B-type linkages in both isolated fractions in the order of the seed shells > cranberry > blueberry. Moreover, the isolated fractions with higher molecular sizes and those more abundant in the proportions of A-type linkages were found to be more effective in the inhibition of pancreatic lipase activity. The results suggest that A-type highly polymeric proanthocyanidins are promising for the attenuation of lipid digestion as dietary supplements.

Antioxidant effects of cranberry powder in lipopolysaccharide treated hypercholesterolemic rats.

Posted: July 25, 2014
Authors: Kim MJ, Kim JH, Kwak HK
Journal: Prev Nutr Food Sci 19(2):75-81

Abstract: This study was conducted to investigate the effects of cranberry power on antioxidant defense system in rats fed an atherogenic diet and injected with lipopolysaccharide (LPS). Sprague-Dawley rats were divided into the following 5 groups: normal diet+saline (NS), atherogenic diet+saline (AS), atherogenic diet+LPS (AL), atherogenic diet with 5% cranberry powder+LPS (AL-C5), and atherogenic diet with 10% cranberry powder+LPS (AL-C10). Total antioxidant status measured by ferric reducing ability of plasma (FRAP) was significantly reduced by LPS injection (24%) and was restored by the cranberry powder treatment (P<0.05). In addition, the mean level of plasma total phenolics was significantly decreased by LPS injection (P<0.05) and tended to be increased when cranberry powder was incorporated in to the diet. Activity of serum superoxide dismutase (SOD) tended to be lowered by LPS injection and declined further in cranberry powder fortified groups. Overall results indicate that dietary cranberry powder may provide appropriate antioxidants to counter the diminished antioxidant status induced by exposing hypercholesterolemic rats to LPS.

Lifespan extension by cranberry supplementation partially requires SOD2 and is life stage independent.

Posted: July 25, 2014
Authors: Sun Y, Yolitz J, Alberico T, Sun X, Zou S
Journal: Exp Gerontol 50:57-63

Abstract: Many nutraceuticals and pharmaceuticals have been shown to promote healthspan and lifespan. However, the mechanisms underlying the beneficial effects of prolongevity interventions and the time points at which interventions should be implemented to achieve beneficial effects are not well characterized. We have previously shown that a cranberry-containing nutraceutical can promote lifespan in worms and flies and delay age-related functional decline of pancreatic cells in rats. Here we investigated the mechanism underlying lifespan extension induced by cranberry and the effects of short-term or life stage-specific interventions with cranberry on lifespan in Drosophila. We found that lifespan extension induced by cranberry was associated with reduced phosphorylation of ERK, a component of oxidative stress response MAPK signaling, and slightly increased phosphorylation of AKT, a component of insulin-like signaling. Lifespan extension was also associated with a reduced level of 4-hydroxynonenal protein adducts, a biomarker of lipid oxidation. Moreover, lifespan extension induced by cranberry was partially suppressed by knockdown of SOD2, a major mitochondrial superoxide scavenger. Furthermore, cranberry supplementation was administered in three life stages of adult flies, health span (3-30 days), transition span (31-60 days) and senescence span (61 days to the end when all flies died). Cranberry supplementation during any of these life stages extended the remaining lifespan relative to the non-supplemented and life stage-matched controls. These findings suggest that cranberry supplementation is sufficient to promote longevity when implemented during any life stage, likely through reducing oxidative damage. Published by Elsevier Inc.

Modulation of strawberry/cranberry phenolic compounds glucuronidation by co-supplementation with onion: characterization of phenolic metabolites in rat plasma using an optimized micro SPE-UHPLC-MS/MS method.

Posted: July 25, 2014
Authors: Dudonne S, Dube P, Pilon G, Marette A, Jacques H, Weisnagel J, Desjardins Y
Journal: J Agric Food Chem 62(14):3244-56

Abstract: Plant phenolic compounds are suggested to exert pharmacological activities in regards to obesity and type-2 diabetes, but their mode of action is poorly understood due to a lack of information about their bioavailability. This work aimed to study the bioavailability of GlucoPhenol phenolic compounds, a strawberry-cranberry extracts blend, by characterizing plasma phenolic profile in obese rats. A comparison was performed by co-supplementation with an onion extract. Using an optimized micro SPE-UHPLC-MS/MS method, 21 phenolic metabolites were characterized, mostly conjugated metabolites and microbial degradation products of the native phenolic compounds. Their kinetic profiles revealed either an intestinal or hepatic formation. Among identified metabolites, isorhamnetin glucuronide sulfate was found in greater amount in plasma. Three glucuronidated conjugates of strawberry-cranberry phenolic compounds, p-hydroxybenzoic acid glucuronide, catechins glucuronide, and methyl catechins glucuronide were found in higher quantities when GlucoPhenol was ingested together with onion extract (+252%, +279%, and +118% respectively), suggesting a possible induction of glucuronidation processes by quercetin. This work allowed the characterization of actual phenolic metabolites generated in vivo following a phenolic intake, the analysis of their kinetics and suggested a possible synergistic activity of phenolic compounds for improving bioavailability.

Supplement timing of cranberry extract plays a key role in promoting Caenorhabditis elegans healthspan.

Posted: July 25, 2014
Authors: Guha S, Natarajan O, Murbach CG, Dinh J, Wilson EC, Cao M, Zou S, Dong Y
Journal: Nutrients 6(2):911-21

Abstract: Consumption of nutraceuticals is a major and potent dietary intervention for delaying aging. As the timing of administration is critical for the efficacy of bioactive compounds in medicine, the effectiveness of nutraceuticals may also be dramatically affected by the timing of supplementation. Cranberry exact (CBE), rich in polyphenols, is consumed as a nutraceutical, and possesses anti-aging properties. Here, we examined the influence of timing on the beneficial effects of CBE supplementation in C. elegans. The prolongevity effect of CBE in different aged worms, young adults, middle-age adults, and aged adults, was determined. Early-start intervention with CBE prolonged the remaining lifespan of worms of different ages more robustly than late-start intervention. The effectiveness of CBE on stress responses and physiological behaviors in different aged worms was also investigated. The early-start intervention prominently promoted motility and resistance to heat shocks and V. cholera infection, especially in aged worms. Together, these findings suggest that the timing of CBE supplementation critically influences its beneficial effects on C. elegans lifespan and healthspan. It is of interest to further investigate whether the similar results would occur in humans.

Urinary excretion of phenolic acids in rats fed cranberry, blueberry, or black raspberry powder.

Posted: July 25, 2014
Authors: Khanal R, Howard LR, Prior RL
Journal: J Agric Food Chem 62(18):3987-96

Abstract: Dietary polyphenolics can be converted into smaller phenolic acids (PA) by microorganisms in the colon and may contribute to health benefits associated with the parent polyphenolics. Urinary excretion of 18 PA and their conjugates was studied, using HPLC-MS/MS, in rats fed AIN93 G-based diets containing 5% (dry weight basis) of either cranberry (CB), blueberry (BB), or black raspberry (BRB). Hippuric, 4-hydroxyphenylacetic, 3-methoxy-4-hydroxyphenylacetic, and 4-hydroxybenzoic acids were excreted in greatest quantity in the urine over a 24 h period in all diets. Primary PA excreted in the berry diets were 4-hydroxycinnamic acid for CB; chlorogenic, ferulic, and 3,4-dihydroxycinnamic acids for BB; and 3-hydroxyphenylpropionic, 3-hydroxybenzoic, and 3-hydroxycinnamic acids for BRB. PA were present in conjugated form with cinnamic acid derivatives being 50-70% and phenylacetic acid derivatives conjugated <10%. Conjugated, and not just the free, PA are significant contributors to total urinary excretion.

Adult cranberry beverage consumers have healthier macronutrient intakes and measures of body composition compared to non-consumers: National Health and Nutrition Examination Survey (NHANES) 2005-2008.

Posted: February 15, 2014
Authors: Duffey KJ, Sutherland LA
Journal: Nutrients 5(12):4938-49

Abstract: Flavonoids, present in high levels in cranberries, are potent bioactives known for their health-promoting benefits, but cranberry beverages (CB) are not typically recommended as part of a healthy diet. We examine the association between CB consumption with macronutrient intake and weight status. Data for US adults (>19 years, n = 10,891) were taken from the National Health and Nutrition Examination Survey (NHANES) Survey 2005-2008. Total CB consumption was measured over two non-consecutive 24-h dietary recalls. Linear and logistic regression models adjusting for important covariates were used to examine predicted differences between CB consumers and non-consumers on macronutrient and anthropometric outcomes. Results are weighted to be nationally representative. CB consumers (n = 581) were older (>50 year) non-Hispanic black females. They consumed an average 221 mL (7.5 oz) CB per day. In fully adjusted models CB consumers (vs. non-consumers) had higher carbohydrates and total sugars and lower percent energy from protein and total fat (all p < 0.001), but no difference in total energy. A significantly higher proportion of CB consumers were predicted to be normal weight (BMI < 25 kg/m2; p = 0.001) and had to have lower waist circumferences (p = 0.001). Although there was not a significant trend across level of CB intake, low and middle level CB consumers compared to non-consumers were more likely to be normal weight (p < 0.001) and less likely to be overweight/obese (BMI > 25 kg/m2, p < 0.001). Despite having slightly higher daily macronutrient intakes, CB consumers have more desirable anthropometric measures compared to non-consumers.

Consumption of cranberry polyphenols enhances human gamma delta -T cell proliferation and reduces the number of symptoms associated with colds and influenza: a randomized, placebo-controlled intervention study.

Posted: February 15, 2014
Authors: Nantz MP, Rowe CA, Muller C, Creasy R, Colee J, Khoo C, Percival SS
Journal: Nutr J 12(161)

Abstract: Background: Our main objective was to evaluate the ability of cranberry phytochemicals to modify immunity, specifically gamma delta -T cell proliferation, after daily consumption of a cranberry beverage, and its effect on health outcomes related to cold and influenza symptoms. Methods: The study was a randomized, double-blind, placebo-controlled, parallel intervention. Subjects drank a low calorie cranberry beverage (450 ml) made with a juice-derived, powdered cranberry fraction (n=22) or a placebo beverage (n=23), daily, for 10 wk. PBMC were cultured for six days with autologous serum and PHA-L stimulation. Cold and influenza symptoms were self-reported. Results: The proliferation index of gamma delta -T cells in culture was almost five times higher after 10 wk of cranberry beverage consumption (p<0.001). In the cranberry beverage group, the incidence of illness was not reduced, however significantly fewer symptoms of illness were reported (p=0.031). Conclusions: Consumption of the cranberry beverage modified the ex vivo proliferation of gamma delta -T cells. As these cells are located in the epithelium and serve as a first line of defense, improving their function may be related to reducing the number of symptoms associated with a cold and flu.

Cranberry interacts with dietary macronutrients to promote healthy aging in drosophila

Posted: February 15, 2014
Authors: Wang C, Yolitz J, Alberico T, Laslo M, Sun Y, Wheeler CT, Sun X, Zou S
Journal: J Gerontol A Biol Sci Med Sci doi: 10.1093/gerona/glt161

Abstract: Botanicals possess numerous bioactivities, and some promote healthy aging. Dietary macronutrients are major determinants of life span. The interaction between botanicals and macronutrients that modulates life span is not well understood. Here, we investigated the effect of a cranberry-containing botanical on life span and the influence of macronutrients on the longevity-related effect of cranberry in Drosophila. Flies were supplemented with cranberry on three dietary conditions: standard, high sugar-low protein, and low sugar-high protein diets. We found that cranberry slightly extended life span in males fed with the low sugar-high protein diet but not with other diets. Cranberry extended life span in females fed with the standard diet and more prominently the high sugar-low protein diet but not with the low sugar-high protein diet. Life-span extension was associated with increased reproduction and higher expression of oxidative stress and heat shock response genes. Moreover, cranberry improved survival of sod1 knockdown and dfoxo mutant flies but did not increase wild-type fly's resistance to acute oxidative stress. Cranberry slightly extended life span in flies fed with a high-fat diet. These findings suggest that cranberry promotes healthy aging by increasing stress responsiveness. Our study reveals an interaction of cranberry with dietary macronutrients and stresses the importance of considering diet composition in designing interventions for promoting healthy aging.

Development and validation of a sensitive, high-throughput bioassay for the adhesion of radiolabeled E. coli to uroepithelial cells in vitro.

Posted: February 15, 2014
Authors: Mathison BD, Kimble LL, Kaspar KL, Khoo C, Chew BP
Journal: J Nat Prod 76(9):1605-11

Abstract: Vaccinium macrocarpon (cranberry) products have been used to prevent uropathogenic Escherichia (E.) coli adherence to uroepithelial cells (UEC) and may help reduce risk of urinary tract infection. Reported herein are the development and validation of an assay to assess antiadhesion activity of V. macrocarpon extracts and human urine. P-fimbriated E. coli (CFT073) was labeled with H-uridine, then co-incubated with HTB-4 UEC at a 400:1 ratio. V. macrocarpon extracts (0-17 mg proanthocyanidins/mL) were added to H-labeled E. coli before co-incubating with UEC. The assay yielded a sensitive inhibition curve: the lower limit of detection and half-maximal inhibitory concentration were 0.43 and 1.59 mg proanthocyanidins/mL for V. macrocarpon extract CEP 55; intra- and interassay coefficients of variance were <10% and <15%, respectively. V. macrocarpon extract CEP 3283 showed identical adhesion inhibition. Serial dilutions of urine from human participants who consumed V. macrocarpon beverages showed a linear decrease in antiadhesion activity. Antiadhesion assays conducted with urine from a human intervention study also showed good agreement with results obtained using the hemagglutination assay. Therefore, a sensitive, high-throughput, biologically relevant antiadhesion assay using H-E. coli co-incubated with UEC is reported, which can be used for studying the action of V. macrocarpon bioactives.

Pregnancy outcome after use of cranberry in pregnancy--the Norwegian Mother and Child Cohort Study.

Posted: February 15, 2014
Authors: Heitmann K, Nordeng H, Holst L
Journal: BMC Altern Med 13:345

Abstract: BACKGROUND: Cranberry is one of the most commonly used herbs during pregnancy. The herb has been used traditionally against urinary tract infections. No studies are found that specifically address the risk of malformations after use of cranberry during pregnancy. The aim of the study was to investigate the safety of cranberry use during pregnancy, including any effects on congenital malformations and selected pregnancy outcomes.

METHODS: The study is based on data from The Norwegian Mother and Child Cohort Study including more than 100,000 pregnancies from 1999 to 2008. Information on use of cranberry and socio-demographic factors was retrieved from three self-administered questionnaires completed by the women in pregnancy weeks 17 and 30, and 6 months after birth. Information on pregnancy outcomes was retrieved from the Medical Birth Registry of Norway.

RESULTS: Among the 68,522 women in the study, 919 (1.3%) women had used cranberry while pregnant. We did not detect any increased risk of congenital malformations after use of cranberry. Furthermore, the use of cranberry was also not associated with increased risk for stillbirth/neonatal death, low birth weight, small for gestational age, preterm birth, low Apgar score (<7), neonatal infections or maternal vaginal bleeding in early pregnancy. Although an association was found between use of cranberry in late pregnancy and vaginal bleeding after pregnancy week 17, further sub-analyses of more severe bleeding outcomes did not support a significant risk.

CONCLUSIONS: The findings of this study, revealing no increased risk of malformations nor any of the following pregnancy outcomes; stillbirth/neonatal death, preterm delivery, low birth weight, small for gestational age, low Apgar score and neonatal infections are reassuring. However, maternal vaginal bleeding should be investigated further before any firm conclusion can be drawn. Treatment guidelines on asymptomatic bacteriuria in pregnancy recommend antimicrobial therapy as the first line treatment. According to our data and the outcomes studied, cranberry does not appear to be a harmful adjunctive self-treatment.

Proanthocyanidin A2 purification and quantification of American cranberry (Vaccinium macrocarpon Ait.) products.

Posted: February 15, 2014
Authors: Lee JM
Journal: J Funct Foods 5(1):144-153

Abstract: In this study, five common proanthocyanidin purification techniques were evaluated prior to phloroglucinolysis, followed by HPLC analysis. An optimized purification method was then used to identify and quantify the proanthocyanidins (extension and terminal units of epigallocatechin, catechin, epicatechin, A type trimer, and A type dimer) of commercially available cranberry products (juices, concentrates, tablets, and capsules; n=17). Two size exclusion beads (Toyopearl 4 TSK HW-40C and Sephadex LH-20) were found suitable for proanthocyanidin purification, though proanthocyanidin extension and terminal unit composition was contingent upon the cleanup procedure utilized. These data illustrate that purification methods require consideration prior to conducting any cranberry proanthocyanidin analyses, and have to be accounted for when comparing values between studies. Total proanthocyanidin levels ranged from 11.7 (juice) to 436.4 (tablet) mg/100 mL or 100 g values obtained from Sephadex LH-20 purification, while total anthocyanin levels ranged from 0.54 (juice) to 98.00 (tablet) mg/100 mL or 100 g.

Quantification by UHPLC of total individual polyphenols in fruit juices.

Posted: February 15, 2014
Authors: Diaz-Garcia MC, Obon JM, Castellar MR, Collado J, Alacid M
Journal: Food Chem 138(2-3):938-49

Abstract: The present work proposes a new UHPLC-PDA-fluorescence method able to identify and quantify the main polyphenols present in commercial fruit juices in a 28-min chromatogram. The proposed method improve the IFU method No. 71 used to evaluate anthocyanins profiles of fruit juices. Fruit juices of strawberry, American cranberry, bilberry, sour cherry, black grape, orange, and apple, were analysed identifying 70 of their main polyphenols (23 anthocyanins, 15 flavonols, 6 hydroxybenzoic acids, 14 hydroxycinnamic acids, 4 flavanones, 2 dihydrochalcones, 4 flavan-3-ols and 2 stilbenes). One standard polyphenol of each group was used to calculate individual polyphenol concentration presents in a juice. Total amount of polyphenols in a fruit juice was estimated as total individual polyphenols (TIP). A good correlation (r(2)=0.966) was observed between calculated TIP, and total polyphenols (TP) determined by the well-known colorimetric Folin-Ciocalteu method. In this work, the higher TIP value corresponded to bilberry juice (607.324 mg/100mL fruit juice) and the lower to orange juice (32.638 mg/100mL fruit juice). This method is useful for authentication analyses and for labelling total polyphenols contents of commercial fruit juices. Copyright 2012 Elsevier Ltd. All rights reserved.

The longevity effect of cranberry extract in Caenorhabditis elegans is modulated by daf-16 and osr-1.

Posted: February 15, 2014
Authors: Guha S, Cao M, Kane RM, Savino AM, Zou S, Dong Y
Journal: Age 35(5):1559-74

Abstract: Nutraceuticals are known to have numerous health and disease preventing properties. Recent studies suggest that extracts containing cranberry may have anti-aging benefits. However, little is known about whether and how cranberry by itself promotes longevity and healthspan in any organism. Here we examined the effect of a cranberry only extract on lifespan and healthspan in Caenorhabditis elegans. Supplementation of the diet with cranberry extract (CBE) increased the lifespan in C. elegans in a concentration-dependent manner. Cranberry also increased tolerance of C. elegans to heat shock, but not to oxidative stress or ultraviolet irradiation. In addition, we tested the effect of cranberry on brood size and motility and found that cranberry did not influence these behaviors. Our mechanistic studies indicated that lifespan extension induced by CBE requires the insulin/IGF signaling pathway and DAF-16. We also found that cranberry promotes longevity through osmotic stress resistant-1 (OSR-1) and one of its downstream effectors, UNC-43, but not through SEK-1, a component of the p38 MAP kinase pathway. However, SIR-2.1 and JNK signaling pathways are not required for cranberry to promote longevity. Our findings suggest that cranberry supplementation confers increased longevity and stress resistance in C. elegans through pathways modulated by daf-16 and osr-1. This study reveals the anti-aging property of widely consumed cranberry and elucidates the underpinning mechanisms.

Deconvolution of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry isotope patterns to determine ratios of A-type to B-type interflavan bonds in cranberry proanthocyanidins

Posted: February 15, 2013
Authors: Feliciano RP, Krueger CG, Shanmuganayagam D, Vestling MM, Reed JD
Journal: Food Chem 135(3):1485-93

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

Comparing Procyanidins in Selected Vaccinium Species by UHPLC-MS with Regard to Authenticity and Health Effects

Posted: October 30, 2012
Authors: Jungfer E, Zimmermann BF, Ruttkat A, Galensa R
Journal: J Agric Food Chem 60(38):9688-96

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

Comparison of Health-Relevant Flavanoids in Commonly Consumed Cranberry Products

Posted: October 30, 2012
Authors: Grace MH, Massey AR, Mbeunkui F, Yousef GG, Lila MA
Journal: J Food Sci 77(8):H176-83

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

Cranberry components for the therapy of infectious disease

Posted: April 30, 2012
Authors: Shmuely H, Ofek I, Weiss EI, Rones Z, Houri-Haddad Y
Journal: Curr Opin Biotechnol 23(2):148-52

Abstract: Summary of the in vitro data support a beneficial effect of cranberry or its proanthocyanin constituents by blocking adhesion to and biofilm formation on target tissues of pathogens. In vivo data partially support these beneficial effects. Consumption of various cranberry products benefited young and elderly females in preventing urinary tract infections, and in conjunction with antibiotic treatment in eradicating Helicobacter pylori infections in women. Mouthwash supplemented with an isolated cranberry derivative reduced significantly the caryogenic mutans streptococci. None of the mice infected intranasal with lethal dose of influenza virus and treated with cranberry fraction died after two weeks. Further studies should focus on the active cranberry component as supplement for food and other products especially where whole juice or powder cannot be used.

Investigation on the Protective Effects of Cranberry Against the DNA Damage Induced by Benzo[a]pyrene

Posted: April 30, 2012
Authors: Madrigal-Santillán E, Fragoso-Antonio S, Valadez-Vega C, Solano-Solano G, Pérez CZ, Sánchez-Gutiérrez M, Izquierdo-Vega JA, Gutiérrez-Salinas J, Esquivel-Soto J, Esquivel-Chirino C, Sumaya-Martínez T, Fregoso-Aguilar T, Mendoza-Pérez J, Morales-González J
Journal: Molecules 17(4):4435-51.

Abstract: There are few reports that demonstrate the antigenotoxic potential of cranberries. Although the types of berry fruits consumed worldwide are many, this paper focuses on cranberries that are commonly consumed in Mexico (Vaccinium macrocarpon species). The purpose of the present study is to determine whether cranberry ethanolic extract (CEE) can prevent the DNA damage produced by benzo[a]pyrene (B[a]P) using an in vivo mouse peripheral blood micronucleus assay. The experimental groups were organized as follows: a negative control group (without treatment), a positive group treated with B[a]P (200 mg/kg), a group administered with 800 mg/kg of CEE, and three groups treated with B[a]P and CEE (200, 400, and 800 mg/kg) respectively. The CEE and benzo[a]pyrene were administered orally for a week, on a daily basis. During this period the body weight, the feed intake, and the determination of antigenotoxic potential were quantified. At the end of this period, we continued with the same determinations for one week more (recovery period) but anymore administration of the substances. The animals treated with B[a]P showed a weight increase after the first week of administration. The same phenomenon was observed in the lots combined with B[a]P and CEE (low and medium doses). The dose of 800 mg/kg of CEE showed similar values to the control group at the end of the treatment period. In the second part of the assay, when the substances were not administered, these experimental groups regained their normal weight. The dose of CEE (800 mg/kg) was not genotoxic nor cytotoxic. On the contrary, the B[a]P increases the frequency of micronucleated normochromatic erythrocytes (MNNE) and reduces the rate of polychromatic erythrocytes (PE) at the end of the treatment period. With respect to the combined lots, a significant decrease in the MN rate was observed from the sixth to the eighth day of treatment with the two high doses applied; the highest protection (60%) was obtained with 800 mg/kg of CEE. The same dose showed an anticytotoxic effect which corresponded to an improvement of 62.5% in relation to the animals administered with the B[a]P. In the second period, all groups reached values that have been seen in the control group animals. Our results suggest that the inhibition of clastogenicity of the cranberry ethanolic extract against B[a]P is related to the antioxidant capacity of the combination of phytochemicals present in its chemical composition.

Prolongevity effects of a botanical with oregano and cranberry extracts in Mexican fruit flies: examining interactions of diet restriction and age

Posted: April 30, 2012
Authors: Zou S, Carey JR, Liedo P, Ingram DK, Yu B.
Journal: Age (Dordr) 34(2):269-79

Abstract: Botanicals rich with phytochemicals have numerous health benefits. Dietary restriction (DR) extends lifespan in diverse species. We previously demonstrated that an oregano-cranberry (OC) mixture can promote longevity in the Mexican Fruit fly (Mexfly, Anastrepha ludens Loew). However, little is known about the interaction between botanicals and DR, and the age-dependent effect of botanicals on lifespan and reproduction. Here we investigated these issues by feeding Mexflies a full or DR diet supplemented with or without 2% OC. Lifespan and daily egg production of individual flies were recorded. The effect of short-term OC supplementation was evaluated by implementing the supplementation at three age intervals-young, middle, and old age. We found that OC increased lifespan of Mexflies on the full or DR diet when compared to their respective controls. OC increased reproduction of females on the full diet and, to a lesser extent, on the DR diet. Short-term OC supplementation was not sufficient to extend lifespan for males at all three age intervals nor for females at young and old age intervals. However, OC supplementation at the middle age interval was sufficient to extend lifespan in females, while only OC supplementation at the young age interval increased reproduction in females. Our findings suggest that OC extends lifespan and promotes reproduction partly through DR-independent pathways, and short-term supplementation have varied impact on longevity and reproduction. This also suggests a positive interaction between non-genetic interventions in promoting longevity and provides guidance for using botanicals as aging interventions in humans.

Transport of Cranberry A-type Procyanidin Dimers, Trimers, and Tetramers across Monolayers of Human Intestinal Epithelial Caco-2 Cells.

Posted: April 30, 2012
Authors: Ou K, Percival SS, Zou T, Khoo C, Gu L
Journal: J Agric Food Chem 15;60(6):1390-6

Abstract: A-type procyanidin oligomers in cranberries are known to inhibit the adhesion of uropathogenic bacteria. B-type procyanidins dimers and trimers are absorbed by humans. The absorption of A-type procyanidins from cranberries in humans has not been demonstrated. This study examined the transport of A-type cranberry procyanidin dimers, trimers, and tetramers on differentiated human intestinal
epithelial Caco-2 cell monolayers. Procyanidins were extracted from cranberries and purified using hromatographic methods. Fraction I contained predominantly A-type procyanidin dimer A2 [epicatechin-(2-O-7, 4-8)-epicatechin]. Fraction II contained primarily A-type trimers and tetramers, with B-type trimers, A-type
pentamers, and A-type hexamers being minor components. Fraction I or II in solution were added onto the apical side of the Caco-2 cell membranes. The media at the basolateral side of the membranes were analyzed using HPLC-MSn after 2 h. Data indicated that procyanidin dimer A2 in fraction I and A-type trimers and tetramers in fraction II traversed across Caco-2 cell monolayers with transport ratio of 0.6%, 0.4%, and 0.2%, respectively. This study demonstrated A-type dimers, trimers, and tetramers were transported across Caco-2 cells at low rates, suggesting they could be absorbed by humans after cranberry consumption.

Characterization by high-performance liquid chromatography with diode-array detection coupled to time-of-flight mass spectrometry of the phenolic fraction in a cranberry syrup used to prevent urinary tract diseases, together with a study of its antibacter

Posted: January 17, 2012
Authors: Iswaldi I, Gomez-Caravaca AM, Arraez-Roman D, Uberos J, Lardon M, Segura-Carretero A, Fernandez-Gutierrez A.
Journal: J Pharm Biomed Anal. 58:34-41

Abstract: The phenolic fraction of a commercial cranberry syrup, which is purported to have good properties for the prevention of urinary diseases, has been thoroughly characterized using HPLC-DAD-TOF-MS. A study of its antibacterial activity has also been carried out. For this purpose a new HPLC-DAD-TOF-MS method using negative and positive ionization modes was developed and it was thus possible to identify 34 different compounds, nine of which have been tentatively characterized for the first time in cranberry syrup. It is also important to highlight that different coumarins in this matrix were also determined, which, to our knowledge, have not been found previously in the cranberry. The phenolic fraction obtained by HPLC-DAD was found to be 5.47 mg/mL. Catechin and procyanidins belonging to flavanols were the family of compounds found at the highest concentrations (2.37 mg/mL); flavonols were at a concentration of 1.91 mg/mL and phenolic-acid derivatives were found at the lowest concentration (0.15 mg/mL). With regard to antibacterial activity, the incubation of Escherichia coli with cranberry syrup was found to reduce surface hydrophobicity as a function of the concentration of the extract.

GC-MS determination of flavonoids and phenolic and benzoic acids in human plasma after consumption of cranberry juice

Posted: November 5, 2010
Authors: Zhang K, Zuo Y
Journal: J Agric Food Chem 52(2):222-7

Abstract: A GC-MS method was developed for the determination of various flavonoids and phenolic and benzoic acids in human plasma. The procedure involved the extraction of flavonoids and phenolic and benzoic acids with ethyl acetate, followed by the derivatization of the phenolic and benzoic compounds with BSTFA (N,O-bis(trimethylsilyl) trifluoroacetamide) + TMCS (trimethylchlorosilane) reagent. The trimethylsilyl derivatives formed were separated and quantitated using GC-MS. Twenty flavonoids and phenolic and benzoic compounds have been well separated in the spiked human plasma without any interference. The average recovery was 79.3%. Several phenolic acids such as o-hydroxybenzoic, p-hydroxyphenylacetic, 2,3-dihydroxybenzoic, 2,4-dihydroxybenzoic, ferulic, sinapic, and benzoic acid were identified and quantified in human plasma after consumption of a cranberry juice. This developed method provides a simple, specific, and sensitive technique for the simultaneous determination of flavonoids and phenolic and benzoic acids in human plasma and is suitable for bioavailability and pharmacokinetic studies.

Inhibition of uropathogenic Escherichia coli by cranberry juice: a new antiadherence assay

Posted: November 5, 2010
Authors: Turner A, Chen SN, Joike MK, Pendland SL, Pauli GF, Farnsworth NR
Journal: J Agric Food Chem 53(23):8940-7

Abstract: A combination of microplate technology and turbidity assessment for testing the adherence of P-fimbriated Escherichia coli to human uroepithelial cell line T24, validated with the addition of the known inhibitor 4-O-alpha-D-galactopyranosyl-alpha-D-galactopyranose (galabiose), resulted in a high-throughput, biologically relevant assessment of cranberry (Vaccinium macrocarpon). P-fimbriated ATCC E. coli strains 25922, 29194, and 49161 were inhibited by galabiose. ATCC 29194, a representative urine isolate containing the papGII allele (Class II fimbrial adhesin) and demonstrating the most significant inhibition in the presence of galabiose, was chosen for further testing. In this assay, a low-polarity fraction of cranberry juice cocktail demonstrated dose-dependent inhibition of E. coli adherence. Reported here, for the first time in V. macrocarpon, are 1-O-methylgalactose, prunin, and phlorizin, identified in an active fraction of cranberry juice concentrate. This in vitro assay will be useful for the standardization of cranberry dietary supplements and is currently being used for bioassay-guided fractionation of cranberry juice concentrate.