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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.

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.

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.

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 μSPE-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.

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.

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.

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

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.

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