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Miscellaneous: Animal

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Effect of Vaccinium Macrocarpon on MK-801-Induced Psychosis in Mice.

Posted: 
February 19, 2019
Authors: 
Shukla D, Maheshwari RA, Patel K, Balaraman R, Sen AK.
Journal: 
Indian J Pharmacol. 2018 Sep-Oct;50(5):227-235. doi: 10.4103/ijp.IJP_74_17.
Abstract: 

OBJECTIVES:This study was aimed to investigate the effect of aqueous cranberry extract (ACE) on MK-801-induced psychosis in mice.MATERIALS AND METHODS:MK-801-treated mice were administered ACE (1 and 2 g/kg, p.o.) for 14 days. Various behavioral parameters and neurochemical estimations such as dopamine (DA), 5-hydroxytryptamine (5-HT), norepinephrine (NE), gamma-aminobutyric acid (GABA), glutamate, and glycine as well as markers of oxidative stress such as nitrite levels were measured.RESULTS:Psychosis-induced mice showed a significant elevation of immobility time in forced swim test, locomotor activity, and reduction in time of permanency in rota-rod test, escape latency time in Cook's pole test while treatment with ACE showed a significant alteration in above-mentioned behavioral parameters in MK-801-induced psychosis. Moreover, MK-801-induced psychosis in the mice showed a significant increase in DA, 5-HT, and NA levels and decrease in GABA, glutamate, and glycine levels in the brain. In contrast, treatment with ACE at both doses remarkably altered the neurochemical parameters. In addition, ACE-treated mice showed a substantial reduction in acetylcholinesterase, D-amino acid oxidase enzyme activity, and nitrite levels which were elevated by the administration of MK-801.CONCLUSIONS:Treatment with ACE once for 14 days (1 and 2 g/kg) significantly ameliorated the behavioral symptoms in experimentally induced psychosis by virtue of neuromodulation and decreased oxidative stress.

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

Posted: 
September 4, 2018
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. 57(5):1829-1844,
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.

A Polyphenol-Rich Cranberry Extract Reverses Insulin Resistance and Hepatic Steatosis Independently of Body Weight Loss.

Posted: 
April 4, 2018
Authors: 
Anhe FF; Nachbar RT; Varin TV; Vilela V; Dudonne S; Pilon G; Fournier M; Lecours MA; Desjardins Y; Roy D; Levy E; Marette A.
Journal: 
Molecular Metabolism. 6(12):1563-1573
Abstract: 

OBJECTIVE: Previous studies have reported that polyphenol-rich extracts from various sources can prevent obesity and associated gastro-hepatic and metabolic disorders in diet-induced obese (DIO) mice. However, whether such extracts can reverse obesity-linked metabolic alterations remains unknown. In the present study, we aimed to investigate the potential of a polyphenol-rich extract from cranberry (CE) to reverse obesity and associated metabolic disorders in DIO-mice. METHODS: Mice were pre-fed either a Chow or a High Fat-High Sucrose (HFHS) diet for 13 weeks to induce obesity and then treated either with CE (200mg/kg, Chow+CE, HFHS+CE) or vehicle (Chow, HFHS) for 8 additional weeks. RESULTS: CE did not reverse weight gain or fat mass accretion in Chow- or HFHS-fed mice. However, HFHS+CE fully reversed hepatic steatosis and this was linked to upregulation of genes involved in lipid catabolism (e.g., PPARalpha) and downregulation of several pro-inflammatory genes (eg, COX2, TNFalpha) in the liver. These findings were associated with improved glucose tolerance and normalization of insulin sensitivity in HFHS+CE mice. The gut microbiota of HFHS+CE mice was characterized by lower Firmicutes to Bacteroidetes ratio and a drastic expansion of Akkermansia muciniphila and, to a lesser extent, of Barnesiella spp, as compared to HFHS controls. CONCLUSIONS: Taken together, our findings demonstrate that CE, without impacting body weight or adiposity, can fully reverse HFHS diet-induced insulin resistance and hepatic steatosis while triggering A. muciniphila blooming in the gut microbiota, thus underscoring the gut-liver axis as a primary target of cranberry polyphenols.

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.

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