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.

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.

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.

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 (p0.05) plasma antioxidant capacity; reduced (p0.05) 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 (p0.05) trabecular connectivity, trabecular number, femoral ash; increased (p0.05) trabecular separation in comparison to the SHAM group. Drinking cranberry juice increased (p0.05) 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.

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.

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

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.

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.