Polyphenolic-rich berry fruits are known to activate redox-sensitive cellular signaling molecules such as phosphatidylinositol-3-kinase (PI3 kinase)/kinase B (Akt), resulting in a cascade of downstream signaling pathways. This study investigated the ability of strawberry (SB), wild blueberry (WBB), and cranberry (CB) extracts to induce the activation of PI3 kinase/Akt signaling in vitro in human umbilical endothelial cells (HUVECs) and whether this activation would enhance cell migration and angiogenesis. Anthocyanin profiles of the extracts were characterized using HPLC-ESI/MS, and Akt activation was investigated using the Alpha Screen SureFire assay. The total anthocyanin contents of SB, WBB, and CB extracts were 81.7, 82.5, and 83.0 mg/100 g fresh weight, respectively. SB, WBB, and CB extracts activated Akt in a dose-dependent manner via PI3 kinase and induced cell migration and angiogenesis in vitro in HUVECs. The results from this study suggest that polyphenolics in berry fruits may play a role in promoting vascular health.

Consumption of fruits and the other dietary antioxidants are considered beneficial due to the protection they afford in the pathogenesis associated with oxidative stress. The aim of this study was to evaluate the antioxidative effects of selected fruit extracts (Plums, Apples, Grapes and Cranberries) on human lung fibroblasts (CCD-25LU) exposed to tert-butyl hydroperoxide (tBHP) oxidative stress. Lactate Dehydrogenase (LDH) was used to assess cytotoxicity (cell integrity) and antioxidant enzymes catalase (CAT), glutathione-s-transferase (GST), glutathione peroxidases (GPx) and concentrations of reduced glutathione (GSH) were determined. Results showed that LDH release by cells pretreated with fruits extracts were significantly (p0.05) lower compared to cells treated with tBHP alone. Antioxidant enzymes (CAT, GST and GPx) in cells pretreated with fruit extracts were increased by 2-4 folds compared to cell exposed to tBHP alone. GSH levels which were significantly (p0.05) reduced after exposure to tBHP were restored by pretreatment with fruit extracts. Fruits extracts used in this study protected CCD-25LU against oxidative stress induced by tBHP and reduced cell damage. Consumption of fruits may therefore play a significant role in protection against oxidative induced lung diseases.

Lipid peroxidation inhibition capacity and antiradical activity were evaluated in HPLC fractions of different polarity obtained from two cranberry juices and three extracts isolated from frozen cranberries and pomace containing antho- cyanins, water-soluble and apolar phenolic compounds, respectively. Compounds with close polarities were collected to obtain between three and four fractions from each juice or extract. The cranberry phenols are good free radical-scav- engers, but they were less efficient at inhibiting the lipid peroxidation. Of all the samples tested, the intermediate pola- rity fraction of extract rich in apolar phenolic compounds of fruit presented the highest antiradical activity while the most hydrophobic fractions of the anthocyanin-rich extract from fruit and pomace appeared to be the most efficient at inhibiting the lipid peroxidation. The antioxidant or pro-oxidant activity of fractions increased with the concentration. The phenol polarity and the technological process to manufacture cranberry juice can influence the antioxidant and an- tiradical activities of fractions.

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.

Purpose Cranberry juice (CJ) contains a remarkably high
concentration of polyphenols, considered to be beneficial for cardiovascular and bone health. The current double-blind, randomized study was designed to test whether daily consumption of double-strength Ocean Spray light CJ (2 9 230 ml) over 4 months has beneficial effects on vascular
function and on endothelial progenitor cells (EPCs) carrying the osteoblastic marker osteocalcin in particular.
Methods Atotal of 84 participants (49.5 ± 16.2 years)with
peripheral endothelial dysfunction and cardiovascular risk
factors were enrolled in this double-blind, randomized, controlled trial (69 completed the 4-month protocol—32 in the CJ group and 37 in the placebo group, respectively). Vascular responses to reactive hyperemia were measured non-invasively by peripheral arterial tonometry (EndoPAT). Peripheral blood mononuclear cells were stained for EPC markers, as well as osteocalcin, and counted by flow cytometry. Results Baseline characteristics were similar in bothgroups. The effect of CJ on peripheral endothelial function
and on circulating EPC counts (CD34?/CD133?/KDR?)
did not change during the study. A high percentage of
EPCs expressed osteocalcin (59.4 ± 35.7%). CJ, as compared
to placebo, induced a decrease in the fraction of
EPCs expressing osteocalcin (-8.64 ± 48.98 and
19.13 ± 46.11%, respectively, p = 0.019). Systemic levels
of the adhesion marker ICAM correlated significantly with
the number of EPCs expressing osteocalcin.
Conclusions The study demonstrated that long-term
supplementation of polyphenol-rich CJ did not improve
peripheral endothelial function. However, the decrease in
the fraction of osteocalcin? EPCs suggests a potential
beneficial effect of polyphenol-rich CJ.

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.

Cranberries, high in polyphenols, have been associated with several cardiovascular health benefits, although limited clinical trials have been reported to validate these findings. We tested the hypothesis that commercially available low-energy cranberry juice (Ocean Spray Cranberries, Inc, Lakeville-Middleboro, Mass) will decrease surrogate risk factors of cardiovascular disease, such as lipid oxidation, inflammation, and dyslipidemia, in subjects with metabolic syndrome. In a randomized, double-blind, placebo-controlled trial, participants identified with metabolic syndrome (n = 15-16/group) were assigned to 1 of 2 groups: cranberry juice (480 mL/day) or placebo (480 mL/day) for 8 weeks. Anthropometrics, blood pressure measurements, dietary analyses, and fasting blood draws were conducted at screen and 8 weeks of the study. Cranberry juice significantly increased plasma antioxidant capacity (1.5 +/- 0.6 to 2.2 +/- 0.4 mumol/L [means +/- SD], P .05) and decreased oxidized low-density lipoprotein and malondialdehyde (120.4 +/- 31.0 to 80.4 +/- 34.6 U/L and 3.4 +/- 1.1 to 1.7 +/- 0.7 mumol/L, respectively [means +/- SD], P .05) at 8 weeks vs placebo. However, cranberry juice consumption caused no significant improvements in blood pressure, glucose and lipid profiles, C-reactive protein, and interleukin-6. No changes in these parameters were noted in the placebo group. In conclusion, low-energy cranberry juice (2 cups/day) significantly reduces lipid oxidation and increases plasma antioxidant capacity in women with metabolic syndrome. Copyright Copyright 2011 Elsevier Inc. All rights reserved.

Emerging science supports therapeutic roles of strawberries, blueberries, and cranberries in metabolic syndrome, a prediabetic state characterized by several cardiovascular risk factors. Interventional studies reported by our group and others have demonstrated the following effects: strawberries lowering total and LDL-cholesterol, but not triglycerides, and decreasing surrogate biomarkers of atherosclerosis (malondialdehyde and adhesion molecules); blueberries lowering systolic and diastolic blood pressure and lipid oxidation and improving insulin resistance; and low-calorie cranberry juice selectively decreasing biomarkers of lipid oxidation (oxidized LDL) and inflammation (adhesion molecules) in metabolic syndrome. Mechanistic studies further explain these observations as up-regulation of endothelial nitric oxide synthase activity, reduction in renal oxidative damage, and inhibition of the activity of carbohydrate digestive enzymes or angiotensin-converting enzyme by these berries. These findings need confirmation in future studies with a focus on the effects of strawberry, blueberry, or cranberry intervention in clinical biomarkers and molecular mechanisms underlying the metabolic syndrome.

BACKGROUND: Cranberry juice contains polyphenolic compounds that could improve endothelial function and reduce cardiovascular disease risk.
OBJECTIVE: The objective was to examine the effects of cranberry juice on vascular function in subjects with coronary artery disease.
DESIGN: We completed an acute pilot study with no placebo (n = 15) and a chronic placebo-controlled crossover study (n = 44) that examined the effects of cranberry juice on vascular function in subjects with coronary artery disease.
RESULTS: In the chronic crossover study, subjects with coronary heart disease consumed a research preparation of double-strength cranberry juice (54% juice, 835 mg total polyphenols, and 94 mg anthocyanins) or a matched placebo beverage (480 mL/d) for 4 wk each with a 2-wk rest period between beverages. Beverage order was randomly assigned, and participants refrained from consuming other flavonoid-containing beverages during the study. Vascular function was measured before and after each beverage, with follow-up testing >=12 h after consumption of the last beverage. Mean (+/-SD) carotid-femoral pulse wave velocity, a measure of central aortic stiffness, decreased after cranberry juice (8.3 +/- 2.3 to 7.8 +/- 2.2 m/s) in contrast with an increase after placebo (8.0 +/- 2.0 to 8.4 +/- 2.8 m/s) (P = 0.003). Brachial artery flow-mediated dilation, digital pulse amplitude tonometry, blood pressure, and carotid-radial pulse wave velocity did not change. In the uncontrolled pilot study, we observed improved brachial artery flow-mediated dilation (7.7 +/- 2.9% to 8.7 +/- 3.1%, P = 0.01) and digital pulse amplitude tonometry ratio (0.10 +/- 0.12 to 0.23 +/- 0.16, P = 0.001) 4 h after consumption of a single 480-mL portion of cranberry juice.
CONCLUSIONS: Chronic cranberry juice consumption reduced carotid femoral pulse wave velocity-a clinically relevant measure of arterial stiffness. The uncontrolled pilot study suggested an acute benefit; however, no chronic effect on measures of endothelial vasodilator function was found. This trial was registered at clinicaltrials.gov as NCT00553904.

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-α (TNF-α), interleukin (IL)-1β, 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-1β 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.