Fresh cranberries were processed by two pilot-scale methods to recover juice and extracts from cranberry pomace. Press cake was extracted with three successive ethanol soaks followed by decanting in trial 1 versus one ethanol soak and solvent removal by decanting and compressing with the bladder press in trial 2. Yields and recoveries of juice, dry juice solids, press cake, press cake extractives (PCEs), polyphenolics and antioxidant capacity were determined relative to the input material of fresh cranberries or press cake. PCEs from both processes exhibited strong dose-dependant vasorelaxant effects on rat aorta rings with EC50 of 2.3-3.9 micro g/mL and Emax of 96-98%. PCEs contained three to four times the phenolic acids, tartaric esters and antioxidant activities plus five to 10 times the flavonols and anthocyanins of their respective juice powders. The polyphenolic levels were 121-142, 7-10, 9-11 and 10-19 mg equivalents of catechin, caffeic acid, quercetin and cyanidin-3-glucoside/g of extract, respectively. Antioxidant activities of the PCEs and juices were 201-296 and 64-75 mg trolox equivalents/g powder. Juice yields of 47-58% accounted for only 18-50% of the bioactives recovered from whole fruit. Sequential extraction of the press cake with 95% ethanol and removal of the extract with the bladder press favored high recoveries of polyphenolics with increased antioxidant and vasorelaxant benefits.

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.

Beneficial health effects of cranberries (CBs) and wild blueberries (BBs), such as reduced levels of oxidative stress, have been demonstrated in feeding studies. These Vaccinium berries contain high levels of flavonoids; however, the bioavailability of flavonoids is generally low. We investigated the in vitro effects of these berries on intestinal cells, focusing on mitigating oxidative stress and associated reactive oxygen species (ROS). First, we simulated the passage of CB and BB through the gastrointestinal (GI) tract by treating berry homogenates to a battery of digestive enzymes. Then, Caco-2 cells, a model of small intestine epithelial uptake, were exposed to these homogenates for 60 min. Using a cell-free assay, we found that the antioxidant activity in CB homogenates was not affected by these enzymes, but that BB homogenates treated with gut enzymes had 43% lower free-radical quenching activity (P 0.05). However, both of the enzyme-treated homogenates were still able to counteract the ROS-generating ability of H2O2 added exogenously to Caco-2 cells. Berry homogenates also increased mitochondrial metabolic rates at 60 min posttreatment, as measured by MTT assays. Enzyme-treated CB (but not BB) homogenates increased the levels of reduced glutathione (GSH) relative to oxidized glutathione (GSSG), a critical indicator of the cellular redox state (P 0.05). Our data suggest that CBs do not lose their antioxidant ability when passing through the GI tract, and specifically, digested CB may serve to enhance cytoprotective effects in intestinal cells by reducing potential damage caused by free radicals and ROS derived from other food sources

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.

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.

BACKGROUND AND OBJECTIVE: Aggressive periodontitis (AgP) causes rapid periodontal breakdown involving AgP gingival fibroblast production of cytokines [i.e. interleukin (IL)-6, a bone metabolism regulator], and matrix metalloproteinase (MMP)-3. Lipopolysaccharide upregulates fibroblast IL-6 and MMP-3, via transcription factors (i.e. NF-kB). Cranberry (Vaccinium macrocarpon) inhibits lipopolysaccharide-stimulated macrophage and normal gingival fibroblast activities, but little is known of its effects on AgP fibroblasts. Objectives of this study are to use AgP fibroblasts, to determine cytotoxicity of cranberry components or periodontopathogen (Fusobacterium nucleatum, Porphyromonas gingivalis) lipopolysaccharide +/- cranberry components, and effects of cranberry components on lipopolysaccharide-stimulated NF-kB activation and IL-6 and MMP-3 production.
MATERIAL AND METHODS: AgP fibroblasts were incubated = 6 d with high molecular weight non-dialyzable material (NDM) (derived from cranberry juice (1-500 mug/mL) or lipopolysaccharide (1 mug/mL) +/- NDM. Membrane damage and viability were assessed by enzyme activity released into cell supernatants and activity of a mitochondrial enzyme, respectively. Secreted IL-6 and MMP-3 were measured by ELISA. NF-kB p65 was measured via binding to an oligonucleotide containing the NF-kB consensus site. Data were analyzed using analysis of variance and Scheffe's F procedure for post hoc comparisons.
RESULTS: Short-term exposure to NDM, or lipopolysaccharide +/- NDM caused no membrane damage. NDM (= 100 mug/mL) or lipopolysaccharide +/- NDM had no effect on viability = 7 d exposure. NDM (50 mug/mL) inhibited lipopolysaccharide-stimulated p65 (P = 0.003) and constitutive or lipopolysaccharide-stimulated MMP-3 (P = 0.02). NDM increased AgP fibroblast constitutive or lipopolysaccharide-stimulated IL-6 (P = 0.0001), but inhibited normal human gingival fibroblast IL-6 (P = 0.01).
CONCLUSION: Lack of toxicity of low NDM concentrations, and its inhibition of NF-kB and MMP-3, suggest that cranberry components may regulate AgP fibroblast inflammatory responses. Distinct effects of NDM on AgP and gingival fibroblast production of IL-6 (which can have both positive and negative effects on bone metabolism) may reflect phenotypic differences in IL-6 regulation in the two cell types.

The stiffening of arteries is a key step in atherogenesis leading to cardiovascular disease. It has been suggested that dietary polyphenols may be cardioprotective through possible favorable effects on oxidative stress and vascular function. The present study was undertaken in order to examine the effect of consuming low-calorie cranberry juice cocktail (CJC), a source of polyphenols, on arterial stiffness in abdominally obese men. We hypothesize that regular CJC consumption will reduce circulating oxidized low-density lipoproteins concentrations and have a beneficial impact on endothelial function. Thirty-five men (mean age +/- SD: 45 +/- 10 years) were randomly assigned to drink 500 mL CJC/day (27% juice) or 500 mL placebo juice (PJ)/day for 4 weeks in a double-blind crossover design. Augmentation index (AIx), an index of arterial stiffness, was measured by applanation tonometry of the radial artery and the cardiometabolic profile was assessed in each participant before and after each phase of the study. We found no significant difference in AIx changes between men who consumed CJC or PJ for 4 weeks (P = .5820). Furthermore, there was no between-treatment difference in changes in AIx responses to salbutamol (P = .6303) and glyceryl trinitrate (P = .4224). No significant difference was noted in other cardiometabolic variables between men consuming PJ or CJC. However, a significant within group decrease in AIx (mean decrease +/- SE; -14.0 +/- 5.8%, P = .019) was noted following the consumption of 500 mL CJC/day for 4 weeks. Our results indicate that the effect of chronic consumption of CJC on AIx was not significantly different from changes associated with the consumption of PJ. However, the significant within-group decrease in AIx following CJC consumption in abdominally obese men may deserve further investigation.

Epidemiological evidence supports inverse associations between fruit and vegetable intake and incidence of
cardiovascular disease and neurodegeneration. Dietary botanicals with salient health benefits include berries and leafy vegetables. Molecular pharmacology research has ascribed these benefits primarily to phenolic constituents and antioxidant activity. The current investigation sought to eluicidate pharmacologic activity of two novel preparations of berry and spinach extracts in vitro. Blueberry and cranberry exhibited the greatest antioxidant activity. In a dose-dependent manner, a proprietary mixture of cranberry and blueberry extracts inhibited inhibitor of jB kinase b, a central node in inflammatory signal transduction. A proprietary mixture of blueberry, strawberry, and spinach extracts inhibited prolyl endopeptidase, a regulator
of central neuropeptide stability and an emerging therapeutic target in neurology and psychiatry. These results indicate specific molecular targets of blended dietary plants with potential relevance to inflammation and neurological health.

Diets rich in fruit and vegetables promote health and delay the onset of diseases associated with oxidative stress. The benefit, especially of different berries, has been largely attributed to their content of numerous phytochemicals, and their effects in terms of antioxidant capacity are often evaluated chemically by different methods. We have instead used a highly relevant biological model, a modified CAP-e assay (Cell-based Antioxidant Protection in erythrocytes), to evaluate bioefficacy of antioxidants in Swedish berries. Extracts of twelve fruit and berries were analysed both by chemical and biological analyses: apple (Malus domestica, peel), bilberry (Vaccinium myrtillus), black currant (Ribes nigrum), purple chokeberry (Aronia x prunifolia), cranberry (Vaccinium macrocarpon), elderberry (Sambucus nigra), lingonberry (Vaccinium vitis-idaea), raspberry (Rubus idaeus), rose hips (Rosa spp.), sea buckthorn (Hippohae rhamnoides), sloe (Prunus spinosa) and strawberry (Fragaria x ananassa). Purple chokeberry, sloe and rose hips showed high antioxidant capacity in the chemical assays. Rose hips showed the highest degree of antioxidant protection also in the biological model, however, chokeberry and sloe showed medium or low protection. Furthermore, strawberry showed overall high protection in the biological assay but low antioxidant capacity in the chemical assays. The chemical and biological models showed different results and future studies of the biological model and in vivo situations are necessary.

The purpose of this study was to determine the total phenol content, antioxidant activity and cytotoxicity of methanol extracts from cranberry plants. The highest total phenol content of 17.1 mg/100 g, and antioxidant activity with IC50=23.8 mg/100 g. This situation shows that the total content of phenolic plant extracts examined correlated with DPPH activity. IC50 cytotoxicity of methanol extracts of each 75.11 micro g/mL against Calu-6 cells, 177.53 from micro g/mL against MCF-cells and 54.87 micro g/mL against HCT-116 cells. From the data obtained we can conclude that this plant has a quite high of total phenolic content and antioxidant activity. Correlation between total phenolics increased DPPH free radical scavenging and cytotoxic activities are quite good. The results of this study showed that cranberry plants can be used as the basis for the treatment of some diseases.