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Miscellaneous: Animal

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Co-Supplementation of Isomalto-Oligosaccharides Potentiates Metabolic Health Benefits of Polyphenol-Rich Cranberry Extract in High Fat Diet-Fed Mice Via Enhanced Gut Butyrate Production.

Posted: 
April 4, 2018
Authors: 
Singh DP; Singh S; Bijalwan V; Kumar V; Khare P; Baboota RK; Singh P; Boparai RK; Singh J; Kondepudi KK; Chopra K; Bishnoi M.
Journal: 
Eur J Nutr. doi: 10.1007/s00394-017-1561-5
Abstract: 

PURPOSE: Cranberries are a rich source of polyphenolic antioxidants. Purified sugars or artificial sweeteners are being added to cranberry-based food products to mask tartness. Refined sugar and artificial sweeteners intake modulate gut microbiota and result in metabolic complications. We evaluated effects of isomalto-oligosaccharides (IMOs; sweet tasting non-digestible oligosaccharides) with cranberry extract (CRX) on high fat diet (HFD)-induced metabolic alterations in mice. METHODS: Male Swiss albino mice were fed normal chow or HFD (58% fat kcal), and were administered either CRX (200 mg/kg) alone or in combination with IMOs (1 g/kg). Cecal short-chain fatty acids, abundances of selected (1) butyrate producing, (2) metabolically beneficial, and (3) selective lipopolysaccharides producing gram negative gut bacteria were studied. Further, gut-related histological, biochemical, genomic changes along with circulating pro-/anti-inflammatory markers and systemic obesity-associated metabolic changes were studied. RESULTS: Co-supplementation of CRX and IMOs significantly improved cecal SCFAs, especially butyrate levels, selected butyrate-producing bacteria (clostridial cluster XIVa bacteria) and butyrate kinase expression in HFD-fed mice. The combination also significantly improved gut beneficial bacterial abundance, gut histology and related changes (colon mucin production, gut permeability) as compared to individual agents. It also prevented HFD-induced systemic and tissue inflammation, glucose intolerance and systemic obesity-associated metabolic changes in adipose tissue and liver. The combination of CRX and IMOs appeared more effective in the prevention of HFD-induced gut derangements. CONCLUSION: Combination of CRX and IMOs could be advantageous for normalization of metabolic alterations seen in diet-induced obesity via beneficial modulation of gastrointestinal health.

Efficient Hepatoprotective Activity of Cranberry Extract Against CCl4-Induced Hepatotoxicity in Wistar Albino Rat Model: Down-Regulation of Liver Enzymes and Strong Antioxidant Activity.

Posted: 
April 4, 2018
Authors: 
Hussain F; Malik A; Ayyaz U; Shafique H; Rana Z; Hussain Z.
Journal: 
Asian Pacific Journal of Tropical Medicine. 10(11):1054-1058
Abstract: 

OBJECTIVE: To investigate the hepatoprotective efficacy of cranberry extract (CBE) against carbon tetrachloride (CCl4)-induced hepatic injury using in-vivo animal model. METHODS: The hepatoprotective efficacy of CBE (200 and 400 mg/kg) was investigated against CCl4 (4 mL/kg)-induced hepatotoxicity, elevated liver enzymes [ALT (alanine aminotransferase), AST (aspartate aminotransferase), and alkaline phosphatase (ALP)], and total protein (TP) contents in the serum. Moreover, CBE-aided antioxidant defense against hepatotoxic insult of CCl4 was measured by evaluating a number of anti-oxidative biomarkers including reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) in the serum by using spectrophotometric analyses. RESULTS: Results showed that the exposure of experimental animals to CCl4 did induce significant hepatotoxicity compared to the non-induced (untreated) group. The oral administration of CBE demonstrated a significant dose-dependent alleviation in the liver enzymes (AST, ALT, and ALP), increased antioxidant defense (GSH, SOD, and CAT), and reduced MDA levels in the serum of treated animals compared to the animals without treatment. The resulting data showed that the administration of CBE decreased the serum levels of ALT, AST, and ALP compared to the CCl4-induced group. CONCLUSIONS: The resulting data evidenced that CBE exhibits promising hepatoprotective potential against the chemical induced hepatotoxicity, maintains homeostasis in liver enzymes, and can provide significant antioxidant defense against free radicals-induced oxidative stress.

The Ameliorative Role of Cranberry Extract and Bone Marrow Cells Against Chlorambucil Cytotoxicity in Rat Fertility

Posted: 
April 4, 2018
Authors: 
Nafie, E. H. O. Khater, E. Awwad, M. Zowail, M. Hegazy, K.
Journal: 
African Journal of Biotechnology; 2017. 16(6):274-279
Abstract: 

The objective of the current study was to evaluate and compare the effectiveness of cranberry extracts and bone marrow cells against chlorambucil (CHB) effect on rats' fertility. Forty adult male albino rats were divided randomly into eight equal groups as the following; normal control, rats injected orally with 0.2 mg/kg of CHB for 14 days, rats injected orally with 100 mg/kg of cranberry extract (CB) for ten days, rats intravenously injected with bone marrow cells (BMC) through tail vain, rats protected with both CB and BMC, rats treated with CHB+CB, rats treated with CHB+BMC and rats treated with CHB+BMC+CB. Genotoxicity were evaluated by counting and comparing the value of sperm abnormalities and normal sperm count. Results show that rats injected with CHB had remarkable increase in sperm head abnormalities as without hook, banana shape and hummer shape. Admission of cranberry extract and bone marrow cells after chemotherapy improved the frequency of the sperm abnormalities.

Anti-Aging and Redox State Regulation Effects of A-type Proanthocyanidins-Rich Cranberry Concentrate and its Comparison with Grape Seed Extract in Mice.

Posted: 
August 15, 2017
Authors: 
Jiao JJ, Wei Y, Chen J, Chen X, Zhang Y.
Journal: 
Journal of Functional Foods 30:63-73
Abstract: 

We investigated the anti-aging and redox state regulation effects by A-type proanthocyanidins (PACs)-rich cranberry concentrate (CBC) and its comparison with B-type PACs-rich grape seed extract (GSE). Using the Q-Extractive mass spectrometry, PACs dimer A and B were identified as predominant phenolic compounds of CBC and GSE, respectively, while epicatechin was present in both extracts. Using the d-galactose-induced aging mice model, effects were investigated via an 8-week oral gavage considering water-soluble vitamin E as the positive control. Both CBC and GSE reduced hepatic and brain thiobarbituric acid reactive substances, and plasma 8-isoprostane levels by 30-57%, 24-30% and 11-62%, respectively, and decreased brain and plasma monoamine oxidase activities by 27-59% and 65-71%, respectively. CBC could improve hepatic glutathione peroxidase activity by 42%, while GSE increased hepatic superoxide dismutase activity by 13%. Therefore, both extracts exerted anti-aging effects probably via regulating in vivo redox state. However, neither generated any effect on catalase activities.

Cranberry (Vaccinium macrocarpon) Extract Treatment Improves Triglyceridemia, Liver Cholesterol, Liver Steatosis, Oxidative Damage and Corticosteronemia in Rats Rendered Obese by High Fat Diet.

Posted: 
August 15, 2017
Authors: 
Peixoto TC; Moura EG; de Oliveira E; Soares PN; Guarda DS; Bernardino DN; Ai XX; Rodrigues VDST; de Souza GR; da Silva AJR; Figueiredo MS; Manhaes AC; Lisboa PC.
Journal: 
European Journal of Nutrition DOI 10.1007/s00394-017-1467-2
Abstract: 

PURPOSE: Obese individuals have higher production of reactive oxygen species, which leads to oxidative damage. We hypothesize that cranberry extract (CE) can improve this dysfunction in HFD-induced obesity in rats since it has an important antioxidant activity. Here, we evaluated the effects of CE in food intake, adiposity, biochemical and hormonal parameters, lipogenic and adipogenic factors, hepatic morphology and oxidative balance in a HFD model. METHODS: At postnatal day 120 (PN120), male Wistar rats were assigned into two groups: (1) SD (n = 36) fed with a standard diet and (2) HFD (n = 36), fed with a diet containing 44.5% (35.2% from lard) energy from fat. At PN150, 12 animals from SD and HFD groups were killed while the others were subdivided into four groups (n = 12/group): animals that received 200 mg/kg cranberry extract (SD CE, HFD CE) gavage/daily/30 days or water (SD, HFD). At PN180, animals were killed.RESULTS: HFD group showed higher body mass and visceral fat, hypercorticosteronemia, higher liver glucocorticoid sensitivity, cholesterol and triglyceride contents and microsteatosis. Also, HFD group had higher lipid peroxidation (plasma and tissues) and higher protein carbonylation (liver and adipose tissue) compared to SD group. HFD CE group showed lower body mass gain, hypotrygliceridemia, hypocorticosteronemia, and lower hepatic cholesterol and fatty acid synthase contents. HFD CE group displayed lower lipid peroxidation, protein carbonylation (liver and adipose tissue) and accumulation of liver fat compared to HFD group. CONCLUSION: Although adiposity was not completely reversed, cranberry extract improved the metabolic profile and reduced oxidative damage and steatosis in HFD-fed rats, which suggests that it can help manage obesity-related disorders.

Morphometric Abnormalities in Spleen and Kidney of the Progeny of Mice Fed American Cranberry Extract (Vaccinium macrocarpon) During Pregnancy and Lactation.

Posted: 
August 15, 2017
Authors: 
Bałan BJ, Lewicki S, Siwicki AK, Stelmasiak M, Skopiński P, Skopińska-Różewska E, Wasiutyński A, Zdanowski R.
Journal: 
Pol J Vet Sci. 20(1):57-65
Abstract: 

Cranberries and cranberry-derived diet supplements are often recommended for the treatment of urinary tract infections, also during pregnancy. These products contain strongly anti-angiogenic chemical compounds which could not be indifferent to the developing fetus. In the present work we evaluated the effect of feeding pregnant and lactating mice American cranberry extract (daily dose 0.88 mg) on the morphology and some parameters of spleen and kidney function of their adult progeny. Six weeks after delivery the morphometry of spleen and kidney, cytometric analysis of spleen lymphocytes, evaluation of humoral response to SRBC (Sheep Red Blood Cells), and examination of serum creatinine/urea concentration, were performed in the offspring. Spleens of progeny from experimental (E) group differed from the spleens of progeny of control mice in the lower number of lymphatic nodules and their larger diameter. Cytometry of spleen cells from progeny of E mothers revealed more CD19+ and CD8+ lymphocytes than in the control group. No difference was seen in the response to immunization by red blood cells of sheep (SRBC) between control and E offspring. An increase in the diameter of glomeruli was observed in the kidneys of the experimental group in comparison with the control group. No abnormalities in creatinine and urea serum level were observed. A higher concentration of VEGF and bFGF in E offspring sera in comparison to the controls was seen. CONCLUSION: Although the observed differences between the control and experimental group were not large, caution is recommended in using cranberries and their extracts during pregnancy until more research will be done on this topic.

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.

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.

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