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Cranberry Anthocyanin as an Herbal Medicine Lowers Plasma Cholesterol by Increasing Excretion of Fecal Sterols.

Posted: September 4, 2018
Authors: Wang L, Zhu H, Zhao Y, Jiao R, Lei L, Chen J, Wang X, Zhang Z, Huang Y, Wang T, Chen ZY.
Journal: Phytomedicine; 38:98-106

Abstract: Background: Interest in using herbal medicines to treat the hypercholesterolemia is increasing. Cranberry extract could decrease plasma cholesterol, however, the active ingredients and the underlying mechanisms remain largely unknown. Hypothesis: The present study was to test the hypothesis that cranberry anthocyanins (CrA) were at least one of the active ingredients responsible for the cholesterol-lowering activity of cranberry fruits via a mechanism of increasing fecal sterol excretion. Methods: Forty-four hamsters were randomly divided into five groups and fed one of the five diets, namely a non-cholesterol control diet (NCD), a high-cholesterol control diet (HCD), a HCD diet supplemented with a low dose of 1% CrA (CL), a HCD diet supplemented with a high dose of 2% CrA (CH), and a HCD diet supplemented with 0.5% cholestyramine as a positive control drug (P-CTL), respectively, for six weeks. Plasma lipoprotein cholesterol was quantified using the enzymatic kits, while the gene expressions of transporters, enzymes and receptors involved in cholesterol absorption and metabolism were quantified using the quantitative RT-PCR. Fecal sterols were quantified using gas chromatography (GC). Results: Plasma total cholesterol and aorta atherosclerotic plaque decreased dose-dependently with the increasing amounts of CrA added into diets. This was accompanied by a dose-dependent increase in excretion of both neutral and acidic sterols. CrA had no effect on the mRNA levels of intestinal Niemann-Pick C1 like 1 protein (NPC1 L1), acyl CoA:cholesterol acyltransferase2 (ACAT2), microsomal triacylglycerol transport protein (MTP), and ATP binding cassette transporter 5 (ABCG5) as well as hepatic cholesterol-7 alpha -hydroxylase (CYP7A1), 3-Hydroxy-3-methylglutaryl reductase (HMG-CoA-R), sterol regulatory element binding protein 2 (SREBP2), LDL receptor (LDL-R), and Liver X receptor alpha (LXR alpha ). Conclusion: CrA as an herbal medicine could favorably modify the lipoprotein profile in hamsters fed a high cholesterol diet by enhancing excretion of fecal neutral and acidic sterols, most likely not mediated by interaction with genes of transporters, enzymes and proteins involved in cholesterol absorption and metabolism

Synergistic Effect of Cranberry Extract and Losartan Against Aluminium Chloride-Induced Hepatorenal Damage Associated Cardiomyopathy in Rats.

Posted: September 4, 2018
Authors: Galal SM; Hasan HF; Abdel-Rafei MK; El Kiki SM.
Journal: Archives of Physiology & Biochemistry. 1-10, 10.1080/13813455.2018.1465437 [doi]

Abstract: The present study was designed to evaluate the effect of cranberry extract (CRAN) and/or losartan (LOS) against aluminium chloride (AlCl3) induced hepatorenal damage associated cardiomyopathy in rats. To induce hepatorenal and cardiotoxicity, animals were received (AlCl3; 70mg/kg i.p.) for 8weeks day after day and treated with CRAN (100mg/kg b.wt.) orally daily for 4weeks started after 4weeks from AlCl3 injection accompanied with an administration of LOS (5mg/kg i.p.) three times weekly for 4weeks. Our data revealed that, compared to AlCl3, administration of CRAN extract and LOS produced a significant improvement which was evidenced by a significant amelioration in myocardial and vascular indices, kidney and liver markers, lipid profile and oxidative stress indices. Furthermore, histopathological and immunohistochemical examination reinforced the previous results. It could be concluded that combination of CRAN extract and LOS hindered AlCl3 induced hepatorenal damage complicated cardiomyopathy in rats.

Cranberry Extract Attenuates Hepatic Inflammation in High-Fat-Fed Obese Mice

Posted: March 1, 2017
Authors: Glisan SL, Ryan C, Neilson AP, Lambert JD
Journal: J Nutr Biochem 37:60-66

Abstract: Cranberry (Vaccinium macrocarpon) consumption has been associated with health beneficial effects. Nonalcoholic fatty liver disease (NAFLD) is a comorbidity of obesity. In the present study, we investigated the effect of a polyphenol-rich cranberry extract (CBE) on hepatic inflammation in high fat (HF)-fed obese C57BL/6J mice. Following dietary treatment with 0.8% CBE for 10 weeks, we observed no change in body weight or visceral fat mass in CBE-supplemented mice compared to HF-fed control mice. We did observe a significant decrease in plasma alanine aminotransferase (31%) and histological severity of NAFLD (33% decrease in area of involvement, 29% decrease in lipid droplet size) compared to HF-fed controls. Hepatic protein levels of tumor necrosis factor alpha and C-C chemokine ligand 2 were reduced by 28% and 19%, respectively, following CBE supplementation. CBE significantly decreased hepatic mRNA levels of toll-like receptor 4 (TLR4, 63%) and nuclear factor kappa B (NF kappa B, 24%), as well as a number of genes related to the nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing 3 inflammasome. In conclusion, CBE reduced NAFLD and hepatic inflammation in HF-fed obese C57BL/6J mice. These effects appear to be related to mitigation of TLR4-NF kappa B related signaling; however, further studies into the underlying mechanisms of these hepatoprotective effects are needed.

Polyphenol Extracts Interfere with Bacterial Lipopolysaccharide in Vitro and Decrease Postprandial Endotoxemia in Human Volunteers

Posted: March 1, 2017
Authors: Wong X, Madrid AM, Tralma K, Castillo R, Carrasco-Pozo C, Navarrete P, Beltran C, Pastene E, Gotteland M
Journal: Journal of Functional Foods; 2016. 26:406-417

Abstract: The intestinal absorption of bacterial lipopolysaccharide (LPS) and dietary fat has been implicated in the development of metabolic endotoxemia. This study first compared the ability of polyphenol extracts from grape, cranberry, avocado and apple to interfere with pancreatic lipase and LPS in vitro. The grape extract displayed a higher inhibitory activity of lipase (IC50=8.6+or-1.1 mg/ml) and LPS binding (IC50=90+or-1.1 micro g/ml). Then, a study was carried out in 12 normal weight and 17 overweight/obese subjects to determine the effect of this extract on the postprandial changes in plasma triacylglycerols, LPS and IL-6. The presence of small intestine bacterial overgrowth (SIBO), in which higher levels of bacteria and eventually LPS are present in the upper intestine, i.e. where dietary fat absorption occurs, was also evaluated. Compared with placebo, the grape extract did not affect postprandial triacylglycerolemia but decreased plasma LPS, without affecting the IL-6-associated inflammatory response. SIBO did not affect these variables.

Anti-inflammatory Activity of Berry Fruits in Mice Model of Inflammation is Based on Oxidative Stress Modulation

Posted: August 22, 2016
Authors: Nardi GM; Farias Januario AG; Freire CG; Megiolaro F; Schneider K; Perazzoli MR; Do Nascimento SR; Gon AC; Mariano LN; Wagner G; Niero R; Locatelli C
Journal: Pharmacognosy Research. 8(Suppl 1):S42-9

Abstract: BACKGROUND: Many fruits have been used as nutraceuticals because the presence of bioactive molecules that play biological activities. OBJECTIVE: The present study was designed to compare the anti-inflammatory and antioxidant effects of methanolic extracts of Lycium barbarum (GOJI), Vaccinium macrocarpon (CRAN) and Vaccinium myrtillus (BLUE). MATERIALS AND METHODS: Mices were treated with extracts (50 and 200 mg/kg, p.o.), twice a day through 10 days. Phytochemical analysis was performed by high-performance liquid chromatography. Antioxidant activity was determine by 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, reducing power, lipid peroxidation thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH) and catalase (CAT) activity. Anti-inflammatory activity was evaluated by paw edema followed by determination of myeloperoxidase (MPO) and TBARS. RESULTS: High amount of phenolic compounds, including rutin, were identified in all berries extracts. However, quercetin was observed only in BLUE and CRAN. GOJI presents higher scavenging activity of DPPH radical and reducing power than BLUE and CRAN. The extracts improved antioxidant status in liver; BLUE showed the largest reduction (75.3%) in TBARS when compared to CRAN (70.7%) and GOJI (65.3%). Nonetheless, CAT activity was lower in BLUE group. However, hepatic concentrations of GSH were higher in animals treated with GOJI rather than CRAN and BLUE. Despite all fruits caused a remarkable reduction in paw edema and TBARS, only BLUE and CRAN were able to reduce MPO. CONCLUSION: These results suggest that quercetin, rutin, or other phenolic compound found in these berry fruits extracts could produce an anti-inflammatory response based on modulation of oxidative stress in paw edema model. SUMMARY: Within fruits broadly consumed because of its nutraceuticals properties include, Lycium barbarum (Goji berry), Vaccinium myrtillus (Blueberry or Bilberry) and Vaccinium macrocarpon (Cranberry)The objectives of this study were the investigation and comparison of chemical composition, antioxidant activity "in vitro" and "in vivo" and anti inflammatory property of berry fruits bought dry form.In summary, two main findings can be addressed with this study: (1) Berry fruits presented antioxidant and anti inflammatory activities "in vitro" and "in vivo"; (2) the extracts of GOJI, CRAN, and BLUE modulate the inflammatory process by different mechanisms.

Cranberry flavonoids prevent toxic rat liver mitochondrial damage in vivo and scavenge free radicals in vitro.

Posted: September 28, 2015
Authors: Lapshina EA, Zamaraeva M, Cheshchevik VT, Olchowik-Grabarek E, Sekowski S, Zukowska I, Golovach NG, Burd VN, Zavodnik IB
Journal: Cell Biochem Funct 33(4):202-10

Abstract: The present study was undertaken for further elucidation of the mechanisms of flavonoid biological activity, focusing on the antioxidative and protective effects of cranberry flavonoids in free radical-generating systems and those on mitochondrial ultrastructure during carbon tetrachloride-induced rat intoxication. Treatment of rats with cranberry flavonoids (7mg/kg) during chronic carbon tetrachloride-induced intoxication led to prevention of mitochondrial damage, including fragmentation, rupture and local loss of the outer mitochondrial membrane. In radical-generating systems, cranberry flavonoids effectively scavenged nitric oxide (IC50 =4.4+/-0.4micro g/ml), superoxide anion radicals (IC50 =2.8+/-0.3micro g/ml) and hydroxyl radicals (IC50 =53+/-4micro g/ml). The IC50 for reduction of 1,1-diphenyl-2-picrylhydrazyl radicals (DPPH) was 2.2+/-0.3micro g/ml. Flavonoids prevented to some extent lipid peroxidation in liposomal membranes and glutathione oxidation in erythrocytes treated with UV irradiation or organic hydroperoxides as well as decreased the rigidity of the outer leaflet of the liposomal membranes. The hepatoprotective potential of cranberry flavonoids could be due to specific prevention of rat liver mitochondrial damage. The mitochondria-addressed effects of flavonoids might be related both to radical-scavenging properties and modulation of various mitochondrial events.

Great heterogeneity of commercial fruit juices to induce endothelium-dependent relaxations in isolated porcine coronary arteries: role of the phenolic content and composition.

Posted: September 28, 2015
Authors: Auger C, Pollet B, Arnold C, Marx C, Schini-Kerth VB
Journal: J Med Food 18(1):128-36

Abstract: Since polyphenol-rich products such as red wine, grape juice, and grape extracts have been shown to induce potent endothelium-dependent relaxations, we have evaluated whether commercial fruit juices such as those from berries are also able to induce endothelium-dependent relaxations of isolated coronary arteries and, if so, to determine whether this effect is related to their phenolic content. Among the 51 fruit juices tested, 2/12 grape juices, 3/7 blackcurrant juices, 4/5 cranberry juices, 1/6 apple juices, 0/5 orange juices, 2/6 red fruit and berry juices, 3/6 blends of red fruit juices, and 0/4 non-red fruit juices were able to induce relaxations achieving more than 50% at a volume of 1%. The active fruit juices had phenolic contents ranging from 0.31 to 1.86g GAE/L, which were similar to those of most of the less active juices with the exception of one active grape juice (2.14g GAE/L) and one active blend of red fruit juices (3.48g GAE/L). Altogether, these findings indicate that very few commercial fruit juices have the ability to induce potent endothelium-dependent relaxations, and that this effect is not related to their quantitative phenolic content, but rather to their qualitative phenolic composition.

Cranberry proanthocyanidins improve intestinal sIgA during elemental enteral nutrition.

Posted: July 25, 2014
Authors: Pierre JF, Heneghan AF, Feliciano RP, Shanmuganayagam D, Krueger CG, Reed JD, Kudsk KA
Journal: JPEN J Parenter Enteral Nutr 38(1):107-14

Abstract: BACKGROUND: Elemental enteral nutrition (EEN) decreases gut-associated lymphoid tissue (GALT) function, including fewer Peyer's patch lymphocytes and lower levels of the tissue T helper 2 (Th2) cytokines and mucosal transport protein polymeric immunoglobulin receptor (pIgR), leading to lower luminal secretory immunoglobulin A (sIgA) levels. Since we recently demonstrated that cranberry proanthocyanidins (PACs) maintain the Th2 cytokine interleukin (IL)-4 when added to EEN, we hypothesized the addition of PACs to EEN would normalize other GALT parameters and maintain luminal levels of sIgA.

METHODS: Institute of Cancer Research mice were randomized (12/group) to receive chow, EEN, or EEN + PACs (100 mg/kg body weight) for 5 days, starting 2 days after intragastric cannulation. Ileum tissue was collected to measure IL-4 by enzyme-linked immunosorbent assay, pIgR by Western blot, and phosphorylated STAT-6 by microarray. Intestinal wash fluid was collected to measure sIgA by Western blot.

RESULTS: Compared with chow, EEN significantly decreased tissue IL-4, phosphorylated STAT-6, and pIgR. The addition of PACs to EEN prevented these alterations. Compared with chow, EEN resulted in significantly lower levels of luminal sIgA. The addition of PACs to EEN increased luminal sIgA levels compared with EEN alone.

CONCLUSIONS: This study suggests the addition of PACs to EEN may support GALT function and maintain intestinal sIgA levels compared with EEN administration alone.

Chronic cranberry juice consumption restores cholesterol profiles and improves endothelial function in ovariectomized rats.

Posted: September 15, 2013
Authors: Yung LM, Tian XY, Wong WT, Leung FP, Yung LH, Chen ZY, Lau CW, Vanhoutte PM, Yao X, Huang Y
Journal: Eur J Nutr 52(3):1145-55

Abstract: PURPOSE: Postmenopausal women experience higher risks for cardiovascular diseases than age-matched men and pre-menopausal women. There is a need for better treatment strategy for estrogen-deficient-related cardiovascular complications. We and others have recently reported that activated renin-angiotensin system and the associated oxidative stress impaired endothelium-dependent relaxation in ovariectomized rat, while angiotensin receptor blocker rescues endothelial dysfunction. Dietary supplements and lifestyle modifications provide an alternative way to improve cardiovascular health. The present study tests the hypothesis that chronic cranberry juice consumption improves cholesterol profiles and vascular functions in estrogen-deficient animal model. The effect of cranberry consumption on expression and activity of renin-angiotensin system in the vasculature will be determined.
METHODS: Ovariectomized rats were treated daily with commercial cranberry juice at 7 mg/kg for 8 weeks, a dosage comparable to recent clinical studies. Serum was collected for measuring cholesterol levels while aorta was isolated for isometric force assay and expression studies.
RESULTS: Cranberry juice consumption reduced circulating levels of total cholesterol, triacylglycerols, HDL, nHDL, and nHDL/HDL ratio. Meanwhile, cranberry juice consumption improved endothelium-dependent relaxation in aorta of ovariectomized rats by restoring p-eNOS level (endothelial nitric oxide synthase phosphorylated at ser-1177), reversing the up-regulated levels of renin-angiotensin system markers (angiotensin-converting enzyme, angiotensin II, and angiotensin II type 1 receptor), and normalizing the elevated NAD(P)H oxidase expression and oxidative stress.
CONCLUSIONS: Our data demonstrate the novel cardiovascular benefits of cranberry juice consumption in improving both vascular functions and cholesterol profiles, providing insight into developing cranberry products into useful dietary supplements for postmenopausal women.

Cranberry Proanthocyanidins Improve Intestinal sIgA During Elemental Enteral Nutrition

Posted: September 15, 2013
Authors: Pierre JF, Heneghan AF, Feliciano RP, Shanmuganayagam D, Krueger CG, Reed JD, Kudsk KA
Journal: JPEN J Parenter Enteral Nutr DOI: 10.1177/0148607112473654

Abstract: Background: Elemental enteral nutrition (EEN) decreases gut-associated lymphoid tissue (GALT) function, including fewer Peyer's patch lymphocytes and lower levels of the tissue T helper 2 (Th2) cytokines and mucosal transport protein polymeric immunoglobulin receptor (pIgR), leading to lower luminal secretory immunoglobulin A (sIgA) levels. Since we recently demonstrated that cranberry proanthocyanidins (PACs) maintain the Th2 cytokine interleukin (IL)-4 when added to EEN, we hypothesized the addition of PACs to EEN would normalize other GALT parameters and maintain luminal levels of sIgA. Methods: Institute of Cancer Research mice were randomized (12/group) to receive chow, EEN, or EEN + PACs (100 mg/kg body weight) for 5 days, starting 2 days after intragastric cannulation. Ileum tissue was collected to measure IL-4 by enzyme-linked immunosorbent assay, pIgR by Western blot, and phosphorylated STAT-6 by microarray. Intestinal wash fluid was collected to measure sIgA by Western blot. Results: Compared with chow, EEN significantly decreased tissue IL-4, phosphorylated STAT-6, and pIgR. The addition of PACs to EEN prevented these alterations. Compared with chow, EEN resulted in significantly lower levels of luminal sIgA. The addition of PACs to EEN increased luminal sIgA levels compared with EEN alone. Conclusions: This study suggests the addition of PACs to EEN may support GALT function and maintain intestinal sIgA levels compared with EEN administration alone.

Cranberry proanthocyanidins improve the gut mucous layer morphology and function in mice receiving elemental enteral nutrition

Posted: September 15, 2013
Authors: Pierre JF, Heneghan AF, Feliciano RP, Shanmuganayagam D, Roenneburg DA, Krueger CG, Reed JD, Kudsk KA
Journal: JPEN-Parenter Enter 37(3):401-9

Abstract: BACKGROUND: Lamina propria Th2 cytokines, interleukin (IL)-4 and IL-13, stimulate goblet cell (GC) proliferation and MUC2 production, which protect the intestinal mucosa. Elemental enteral nutrition (EEN) reduces tissue IL-4 and impairs barrier function. Proanthocyanidins (PACs) stimulate oral mucin levels. We hypothesized that adding PAC to EEN would maintain Th2-without stimulating Th1-cytokines and preserve luminal MUC2 vs EEN alone. Materials and
METHODS: Seventy mice were randomized to 5 diet groups-standard chow, intragastric EEN, or EEN with lowPAC, midPAC (50 mg), or highPAC (100 mg PAC/kg BW)-for 5 days, starting 2 days after gastric cannulation. Ileal tissue was analyzed for histomorphology and the cytokines IL-4, IL-13, IL-1, IL-6, and TNF- by enzyme-linked immunosorbent assay. MUC2 was measured in intestinal washes.
RESULTS: EEN lowered IL-13 (P < .05) compared with standard chow, whereas IL-4 was not significant (P < .07). LowPAC and midPAC increased IL-13 (P < .05), whereas highPAC increased both IL-4 and IL-13 (P < .05) compared with EEN. All EEN diets reduced (P < .05) crypt depth compared with the chow group. Compared with standard chow, GC numbers and luminal MUC2 were reduced with EEN (P < .05). These effects were attenuated (P < .05) with midPAC and highPAC. No changes were observed in tissue Th1 cytokines.
CONCLUSIONS: Adding PACs to EEN reverses impaired intestinal barrier function following EEN by improving the gut mucous layer and function through increased GC size and number as well as levels of MUC2 and ileal IL-4 and IL-13.

Lingonberry, cranberry and blackcurrant juices affect mRNA

Posted: April 30, 2012
Authors: Kivimaki AS, Ehlers PI, Siltari A, Turpeinen AM,
Journal: J Funct Food 4;496-503

Abstract: Flavonoids and other phenolic compounds affect low-grade inflammation related to cardiovascular diseases among other positive health effects. Cardioprotective actions are
mainly due to enhanced endothelial function and production of nitric oxide (NO).We investigated vascular anti-inflammatory effects of cranberry (Vaccinium oxycoccos), lingonberry (Vaccinium vitis-idaea) and blackcurrant (Ribes nigrum) juices given as drinking fluid ad
libitum to spontaneously hypertensive rats (SHR), a widely used model of human hypertension, in an 8 week ntervention study. The animals were sacrificed, the aortas cleaned and RNA was extracted. cDNA was prepared for real-time PCR and blood was collected for biochemical
analyses. The mRNA expressions of angiotensin-converting enzyme 1 (ACE1), cyclooxygenase 2 (COX2), monocyte chemoattractant protein 1 (MCP1) and P-selectin were
significantly reduced in the cranberry and lingonberry groups. These findings suggest that cranberry and lingonberry cold-compressed juices have anti-inflammatory and antiatherothrombotic actions in long-term treatment of SHR.

Rat liver mitochondrial damage under acute or chronic carbon tetrachloride-induced intoxication: Protection by melatonin and cranberry flavonoids

Posted: April 30, 2012
Authors: Cheshchevik VT, Lapshina EA, Dremza IK, Zabrodskaya SV, Reiter RJ, Prokopchik NI, Zavodnik IB
Journal: Toxicol Appl Pharmacol http://dx.doi.org/10.1016/j.taap.2012.04.007

Abstract: In current societies, the risk of toxic liver damage hasmarkedly increased. The aim of the presentworkwas to carry out further research into themechanism(s) of livermitochondrial damage induced by acute (0.8 g/kg bodyweight, single injection) or chronic (1.6 g/ kg body weight, 30 days, biweekly injections) carbon tetrachloride induced intoxication and to evaluate the hepatoprotective potential of the antioxidant, melatonin, as well as succinate
and cranberry flavonoids in rats. Acute intoxication resulted in considerable impairment of mitochondrial respiratory parameters in the liver. The activity of mitochondrial succinate dehydrogenase (complex II) decreased (by 25%, pb0.05). Short-term melatonin treatment (10 mg/kg, three times) of rats did not reduce the degree of toxicmitochondrial dysfunction but decreased the enhanced NO production. After 30-day chronic intoxication, no significant change in the respiratory activity of livermitochondria was observed, despite marked changes in the redox-balance ofmitochondria. The activities of themitochondrial enzymes, succinate dehydrogenase and glutathione peroxidase, as well as that of cytoplasmic catalase in liver cells were inhibited significantly. Mitochondria isolated from the livers of the rats chronically treated with CCl4 displayed obvious irreversible impairments. Long-term melatonin administration (10 mg/kg, 30 days, daily) to chronically intoxicated rats diminished the toxic effects of CCl4, reducing elevated plasma activities of alanine aminotransferase and aspartate aminotransferase and bilirubin concentration, prevented accumulation of membrane lipid peroxidation products in rat liver and resulted in apparent preservation of
the mitochondrial ultrastructure. The treatment of the animals by the complex of melatonin (10 mg/kg)
plus succinate (50 mg/kg) plus cranberry flavonoids (7 mg/kg) was even more effective in prevention of
toxic liver injury and liver mitochondria damage.

Effects of freeze-dried cranberry powder on serum lipids and inflammatory markers in lipopolysaccharide treated rats fed an atherogenic diet

Posted: January 22, 2012
Authors: Kim MJ, Ohn J, Kim JH, Kwak HK
Journal: Nutr Res Pract 5(5):404-11

Abstract: This study investigated the effects of freeze-dried cranberry powder on anti-inflammation and lipid profiles of lipopolysaccharide (LPS)-treated rats fed an atherogenic diet for 6 weeks. Forty Sprague-Dawley male rats (6-weeks-old) were equally divided into the following five groups: 1) normal diet group + saline (NC); 2) atherogenic diet + saline (HFC); 3) atherogenic diet + LPS (HL); 4) atherogenic diet with 5% cranberry power + LPS (C5); 5) atherogenic diet with 10% cranberry power + LPS (C10). LPS (0.5 mg/kg) was injected into the abdominal cavities of rats 18 hours prior to sacrifice. At the end of the experimental period, we measured serum lipid profiles as well as levels of serum C-reactive protein (CRP), nitric oxide (NO), and pro-inflammatory cytokines such as tumor necrosis factor-&#945; (TNF-&#945;), interleukin (IL)-1&#946;, IL-6, and IL-10 as an anti-inflammatory cytokine. The mean serum high density lipoprotein (HDL)-cholesterol level in C5 rats was significantly higher than that in NC and HL rats (P < 0.05). The mean serum levels of CRP and IL-1&#946; were significantly lower (P < 0.05) in the cranberry powder groups compared to those in HL rats. Additionally, mean serum IL-6 levels tended to be lower in the cranberry groups than that in the HL group, whereas serum IL-10 and NO showed 29% and 88% higher mean values in the C5 group and 49% and 24% higher in the C10 group than those in the HL group, respectively. These results suggest that freeze-dried cranberry powder may have beneficial effects on cardiovascular diseases by modifying serum lipids and the early inflammatory response.

Fruit juice-induced endothelium-dependent relaxations in isolated porcine coronary arteries: evaluation of different fruit juices and purees and optimization of a red fruit juice blend

Posted: January 22, 2012
Authors: Auger C, Kim JH, Trinh S, Chataigneau T, Popken AM, Schini-Kerth VB.
Journal: Food Funct 2(5):245-50

Abstract: Numerous studies have indicated that several polyphenol-rich sources such as red wine and green tea are potent inducers of endothelium-dependent relaxations in isolated arteries. As various fruits and berries are known to contain high levels of polyphenols, the aim of the present study was to assess the ability of selected pure fruit juices and purees as well as blends to cause endothelium-dependent relaxations in isolated arteries. Vascular reactivity was assessed using porcine coronary artery rings, and fruit juices, purees and blends were characterized for their content in vitamin C, total phenolic, sugar and antioxidant activity. Fruit juices and purees caused variable concentration-dependent relaxations, with blackcurrant, aronia, cranberry, blueberry, lingonberry, and grape being the most effective fruits. Several blends of red fruits caused endothelium-dependent relaxations. Relaxations to blend D involved both a NO- and an EDHF-mediated components. The present findings indicate that some berries and blends of red fruit juices are potent inducers of endothelium-dependent relaxations in the porcine coronary artery. This effect involves both endothelium-derived NO and EDHF, and appears to be dependent on their polyphenolic composition rather than on the polyphenolic content.

Insights into the molecular mechanisms of the anti-atherogenic actions of flavonoids in normal and obese mice.

Posted: January 22, 2012
Authors: Shabrova EV, Tarnopolsky O, Singh AP, Plutzky J, Vorsa N, Quadro L.
Journal: PLoS One 6(10):e24634

Abstract: Obesity is a major and independent risk factor for cardiovascular disease and it is strongly associated with the development of dyslipidemia, insulin resistance and type 2 diabetes. Flavonoids, a diverse group of polyphenol compounds of plant origin widely distributed in human diet, have been reported to have numerous health benefits, although the mechanisms underlying these effects have remained obscure. We analyzed the effects of chronic dietary supplementation with flavonoids extracted from cranberry (FLS) in normal and obese C57/BL6 mice compared to mice maintained on the same diets lacking FLS. Obese mice supplemented with flavonoids showed an amelioration of insulin resistance and plasma lipid profile, and a reduction of visceral fat mass. We provide evidence that the adiponectin-AMPK pathway is the main mediator of the improvement of these metabolic disorders. In contrast, the reduced plasma atherogenic cholesterol observed in normal mice under FLS seems to be due to a downregulation of the hepatic cholesterol synthesis pathway. Overall, we demonstrate for the first time that the molecular mechanisms underlying the beneficial effects of flavonoids are determined by the metabolic state.

Effects of ginger and cranberry

Posted: December 16, 2010
Authors: Liburt NR, McKeever KH, Streltsova JM, Franke WC, Gordon ME, Filho HCM, Horohov DW, Rosen RT, Ho CT, Singh AP, Vorsa N.
Journal: Comp Exerc Physiol 6(4):157-169

Abstract: This study hypothesized that ginger (Zingiber officinale) and cranberry (Vaccinium macrocarpon) extracts would alter the physiological response to exercise as well as markers of muscle damage, and mRNA expression for the inflammatory cytokines tumour necrosis factor-a (TNF-a), interferon-g (IFN-g) and interleukin-6 (IL-6) after an exhaustive bout of exercise in horses. Nine unfit Standardbred mares (age 10 ^ 4 years, ,450 kg) completed three graded exercise tests (GXTs) in a crossover design, where they were assigned to the initial order of treatment in a randomized fashion. The GXTs were conducted between 07.00 and 12.00 hours, 7 days apart. Mares received either water (2 l), cranberry (,30 g in 2 l of water) or ginger (,30 g in 2 l of water) extract 1 h prior to testing. Blood samples were taken prior to dosing (pre-exercise), at the end of each step of the GXT, at the end of the exercise and at 2, 5 and 30 min, 1, 2, 4 and 24 h post-GXT. Plasma total protein (TP) concentration and haematocrit (HCT) were analysed immediately following the tests. Analysis of creatine kinase (CK) and aspartate aminotransferase (AST) was done commercially. There was no effect of treatment (P > 0.05) on VO2max, run-time to fatigue, core temperature, TP or HCT. CK was substantially elevated (P < 0.05) in the ginger group at 4 h post-GXT. All CK levels returned to baseline 24 h post-GXT. No change (P > 0.05) was noted in AST. A slight increase (P < 0.05) in CK was seen in all groups at 2 h post-GXT. The cranberry group had significantly lower TNF-a mRNA expression than the control and ginger groups. Ginger appeared to influence (P < 0.05) the upregulation and expression of IFN-g mRNA at 30 min post-GXT, but, more strikingly, significantly decreased recovery time defined as the time for VO2 to recover from the peak observed at fatigue to a post-exercise plateau (ginger = 101 3 s, water = 130 14 s, cranberry = 131 16 s). No effect of treatment or exercise (P > 0.05) was seen on IL-6 mRNA expression. Results suggest that cranberry extract blunts the upregulation and expression of TNF-a mRNA, while ginger extract reduces cardiovascular recovery time in horses completing a short, exhaustive bout of exercise.

Effects of cranberry powder on serum lipid profiles and biomarkers of oxidative stress in rats fed an atherogenic diet

Posted: November 17, 2010
Authors: Kim MJ, Jung HN, Kim KN, Kwak HK
Journal: Nutr Res Pract 2(3):158-64

Abstract: This study investigated that the antioxidative effect of freeze-dried cranberry powder against protein and lipid oxidation and ameliorative effect of serum lipid profile in rat fed atherogenic diet. Six weeks old male Sprague-Dawley rats were divided into the following four groups: normal diet group with 5% corn oil (control), atherogenic diet group with 5% corn oil, 10% lard, 1% cholesterol, and 0.5% sodium cholate (HFC), atherogenic plus 2% cranberry powder diet group (HFC + C2), and atherogenic plus 5% cranberry powder diet group (HFC + C5), and respective diet and water were fed daily for 6 weeks. After the experimental period, the serum lipid profile, such as total cholesterol, HDL-cholesterol, LDL-cholesterol, and triglyceride, ferric reducing ability of plasma (FRAP), plasma phenolics content, superoxide dismutase (SOD) activity, serum protein carbonyl and thiobarbituric acid reactive substances (TBARS) levels were examined. Total phenolic compound and total flavonoid levels in freeze-dried cranberry powder were 9.94 mg/g and 8.12 mg/g, respectively. Serum total cholesterol and LDL-cholesterol levels were not significantly different for cranberry powder treatment, but serum HDL-cholesterol level was significantly increased in HFC + C5 group compared with HFC group. Plasma FRAP value tended to be increased by cranberry powder treatment though there was no significant difference. Plasma total phenol concentrations and SOD activities were not significantly different among all groups. Serum protein carbonyl and TBARS levels were significantly decreased in HFC + C5 group compared with HFC group. Overall results suggested that freeze-dried cranberry powder might have the serum lipid improving effect, as well as antioxidative effect demonstrated by its protective effect against protein and lipid oxidation.

Cranberry juice improved antioxidant status without affecting bone quality in orchidectomized male rats.

Posted: November 4, 2010
Authors: Villarreal A, Stoecker BJ, Garcia C, Garcia K, Rios R, Gonzales C, Mandadi K, Faraji B, Patil BS, Deyhim F.
Journal: Phytomedicine 14(12):815-20

Abstract: BACKGROUND: We reported that drinking citrus juice improves bone quality in orchidectomized senescent male rats. Because cranberry juice, like citrus, is rich in nutrients and phenolic compounds, beneficial effects of citrus juice might also be seen with cranberry juice. An experiment evaluated effect of drinking cranberry juice on bone quality in orchidectomized rats.

METHODS: Thirty-two 1-year-old male rats were randomized to two groups: a sham-control group (n=8) and an orchidectomized group (n=24). The treatments for the 4 months duration of the study were SHAM, orchidectomy (ORX), ORX+drinking either 27% or 45% cranberry juice concentrate added to drinking water. At the termination of the study, the rats were euthanized, blood was collected for plasma antioxidant status and IGF-I. The femur, tibia and the 4th lumbar were evaluated for bone quality. Total calcium and magnesium concentration in the femurs were also evaluated.

RESULTS: ORX did not affect red blood cell (RBC)-induced hemolysis despite lowering (p<0.05) plasma antioxidant capacity; reduced (p<0.05) plasma IGF-I, femoral density, femoral strength, time-induced femoral fracture, bone mineral content, bone mineral area; numerically (p=0.07) lowered 4th lumbar density; decreased (p<0.05) trabecular connectivity, trabecular number, femoral ash; increased (p<0.05) trabecular separation in comparison to the SHAM group. Drinking cranberry juice increased (p<0.05) plasma antioxidant status, protected RBC against hemolysis, but had no positive effect on bone quality or bone mineral status.

CONCLUSIONS: Cranberry juice increases plasma antioxidant status without affecting bone quality.

Cranberry juice increases antioxidant status without affecting cholesterol homeostasis in orchidectomized rats.

Posted: November 4, 2010
Authors: Deyhim F, Patil BS, Villarreal A, Lopez E, Garcia K, Rios R, Garcia C, Gonzales C, Mandadi K.
Journal: J Med Food 10(1):49-53

Abstract: Oxidative stress and hypogonadism are linked to the increased incidence of cardiovascular disease in males. The objective of this research was to delineate whether drinking cranberry juice for 4 months affects antioxidant capacity and lipid profile in orchidectomized rats. Thirty-two 1-year-old male rats were randomized to two groups: a sham-control group (n = 8) and an orchidectomized group (n = 24). The orchidectomized group was divided into three groups of eight and assigned to one of the following treatments: orchidectomy, orchidectomy plus 27% cranberry juice, and orchidectomy plus 45% cranberry juice. At 120 days after initiation of the study, all rats were killed, blood was collected, and plasma was harvested for total antioxidant status, malondialdehyde, nitrate + nitrite, and superoxide dismutase (SOD) activity in liver, and concentrations of cholesterol and triglyceride in liver and in plasma. Orchidectomy depressed (P < .05) plasma antioxidant capacity and SOD activity, elevated (P < .05) nitrate + nitrite and malondialdehyde in plasma, and increased (P < .05) triglyceride and cholesterol values in liver and in plasma. Cranberry juice increased (P < .05) plasma antioxidant capacity and SOD activity and reduced (P < .05) nitrate + nitrite and malondialdehyde concentrations. Drinking cranberry juice did not affect cholesterol concentrations in liver and in plasma. Triglyceride concentration in plasma of orchidectomized rats that were drinking cranberry juice increased (P < .05), but its concentration in liver decreased (P < .05) to the level of shams. The protective effect of cranberry juice from oxidative damage may be mediated by a decrease in nitrate + nitrite and dose-dependent decrease in peroxidation.

Effects of a flavonol-rich diet on select cardiovascular parameters in a Golden Syrian hamster model.

Posted: November 4, 2010
Authors: Kalgaonkar S, Gross HB, Yokoyama W, Keen CL
Journal: J Med Food 13(1):108-15

Abstract: The concept that the consumption of a diet rich in flavonoids can be associated with a reduced risk for cardiovascular disease is becoming increasingly accepted. In the present study we investigated the effects of the following four diets on blood pressure and cholesterol ester levels in hypercholesterolemic Golden Syrian hamsters: a high-fat, high-cholesterol diet (HFHC); a HFHC with 2% cranberry concentrate powder (HFHC+CE); a HFHC with 0.1% rutin (HFHC+Rutin); and a HFHC with 30 mg/kg vitamin E (HFHC+Vit.E). Diets were fed for either 12 or 20 weeks. Over the experimental period, heart rate and blood pressure measurements increased in the animals fed HFHC and HFHC+Vit.E; in contrast, these measurements were not increased in the animals fed HFHC+CE and HFHC+Rutin. Mesenteric and total abdominal fat were significantly lower in the animals fed HFHC+Rutin than in animals fed the other three diets. Ratios of plasma high-density lipoprotein cholesterol (HDL-C) to very-low-density lipoprotein cholesterol and of plasma HDL-C to low-density lipoprotein cholesterol were significantly higher in animals consuming HFHC+Vit.E than in animals fed the other three diets. Aortic cholesteryl ester levels were significantly lower in animals fed HFHC+CE, HFHC+Rutin, and HFHC+Vit.E at 20 weeks than in the animals fed HFHC. Fasting blood glucose concentrations were significantly lower in animals fed HFHC+Rutin and HFHC+Vit.E, and glucose clearance rates improved in animals fed HFHC+Rutin compared to animals fed the other three diets. Results obtained from this study support the concept that the chronic consumption of a flavonoid-rich diet can be beneficial

Long-term effects of three commercial cranberry products on the antioxidative status in rats: a pilot study.

Posted: November 4, 2010
Authors: Palikova I, Vostalova J, Zdarilova A, Svobodova A, Kosina P, Vecera R, Stejskal D, Proskova J, Hrbac J, Bednar P, Maier V, Cernochova D, Simanek V, Ulrichova J.
Journal: J Agric Food Chem 8(3):1672-8

Abstract: Cranberry (Vaccinium macrocarpon Ait. Ericaceae) fruits and juice are widely used for their antiadherence and antioxidative properties. Little is known however about their effects on clinical chemistry markers after long-term consumption. This study was conducted to evaluate the effect of three commercial cranberry products, NUTRICRAN90S, HI-PAC 4.0, and PACRAN on the antioxidative status of rodents, divided into three experimental groups. The products were given as dietary admixtures (1500 mg of product/kg of stock feed) for 14 weeks to male Wistar rats (Groups 2-4) and a control Group 1 which received only stock feed. There were no significant cranberry treatment-related effects on oxidative stress parameters, catalase, glutathione peroxidase, glutathione reductase, glutathione transferase, superoxide dismutase, total antioxidant capacity, thiobarbituric acid reactive substances, advanced oxidation protein products, total SH-groups, or any other measured clinical chemistry markers. Hematological parameters, body weight, and food consumption were also unaffected by intake of cranberries. Only liver glutathione reductase activity and glutathione levels were significantly lower in Group 4 than in Group 1. Plasma alkaline phosphatase alone was significantly decreased in Group 2. No gross pathology, effects on organ weights, or histopathology were observed. No genotoxicity was found, and total cytochrome P450 level in liver was unaffected in all groups. The levels of hippuric acid and several phenolic acids were significantly increased in plasma and urine in Groups 2-4. The concentration of anthocyanins was under the detection threshold. The dietary addition of cranberry powders for 14 weeks was well tolerated, but it did not improve the antioxidative status in rats.

Cranberry juice induces nitric oxide-dependent vasodilation in vitro and its infusion transiently reduces blood pressure in anesthetized rats

Posted: October 31, 2010
Authors: Maher MA, Mataczynski H, Stefaniak HM and Wilson T
Journal: J Med Food 3(3):141-7

Abstract: ABSTRACT Red wine vasodilates rat aortae, an effect attributed to polyphenolic compounds. Cranberry juice (CBJ) is also rich in polyphenols. We determined that CBJ has vasorelaxing properties similar to those of red wine. Rat aortic rings cleaned in Krebs buffer, pH 7.4, bubbled with 95% O(2) and 5% CO(2) were recovered for 30 minutes at 37 degrees C under 2.0 g tension. After phenylephrine (PE, 100 mumol/L) contraction, acetylcholine (3 mumol/L)-induced relaxation of intact vessel was significantly higher than in denuded vessels (59.1 +/- 0.27% versus 10.1 +/- 0.09% of the maximal PE contraction; P <.003). After a second PE contraction, a 1:100 dilution of CBJ was added. Intact rings were vasodilated by CBJ with 56.7 +/- 0.26% relaxation, compared to denuded rings with 8.9 +/- 0.06% relaxation (P <.002). Addition of L-NAME reversed CBJ-induced vasorelaxation in intact vessels with 0.54 +/- 0.34 g compared to 0.04 +/- 0.04 g in denuded vessels (P <.007). Subsequent addition of L-arginine resulted in a return of vasodilation in intact vessels. Additionally, CBJ infusion at a 1:100 dilution of estimated blood volume resulted in a 16% reduction of mean arterial blood pressure in anesthetized rats. This study suggests that, like red wine, CBJ has the capacity to exert in vitro and in vivo vasodilatory effects.