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Cardiovascular Health & Anti-inflammatory Benefits

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Inhibition of interleukin-17-stimulated interleukin-6 and -8 production by cranberry components in human gingival fibroblasts and epithelial cells.

Posted: 
February 15, 2014
Authors: 
Tipton DA, Cho S, Zacharia N, Dabbous MK
Journal: 
J Periodontal Res 48(5):638-46
Abstract: 

BACKGROUND AND OBJECTIVE: Gingival epithelial cells and fibroblasts participate in periodontal inflammation and destruction, producing interleukin (IL)-6, a regulator of osteoclastic bone resorption, and the neutrophil chemoattractant IL-8. IL-17, a product of T-helper 17 cells, may play a role in periodontitis by stimulating cytokine production by gingival cells. The cranberry (Vaccinium macrocarpon) is rich in polyphenols, particularly proanthocyanidins, which have antioxidant and other beneficial properties. Cranberry components inhibit pro-inflammatory activities of lipopolysaccharide-stimulated human macrophages, gingival fibroblasts, and epithelial cells, but little is known of its effects on IL-17-stimulated cytokine production. The objectives were to determine the effects of IL-17 + cranberry components on IL-6 and IL-8 production by human gingival epithelial cells and fibroblasts.

MATERIAL AND METHODS: Cranberry high molecular weight non-dialyzable material (NDM), which is rich in proanthocyanidins, was derived from cranberry juice. Human gingival epithelial cells and normal human gingival fibroblasts were incubated with NDM (5-50 mug/mL), IL-17 (0.5-100 ng/mL), or NDM + IL-17 in serum-free medium for 6 d. IL-6 and IL-8 in culture supernatants were measured by ELISA. Membrane damage and viability were assessed by lactate dehydrogenase activity released into cell supernatants and activity of a mitochondrial enzyme, respectively. Data were analyzed using ANOVA and Scheffe's F procedure for post hoc comparisons.

RESULTS: In both cell lines, IL-17 (> ~5-10 ng/mL) significantly stimulated production of IL-6 (p

CONCLUSION: Cranberry NDM inhibition of constitutive and IL-17-stimulated IL-6 and IL-8 production by gingival fibroblasts and epithelial cells suggests that cranberry components could be useful as a host modulatory therapeutic agent to prevent or treat periodontitis. 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Relationship between polyphenol content and anti-influenza viral effects of berries.

Posted: 
February 15, 2014
Authors: 
Sekizawa H, Ikuta K, Mizuta K, Takechi S, Suzutani T
Journal: 
J Sci Food Agric 93(9):2239-41
Abstract: 

BACKGROUND: Berries are known to have many kinds of biological activities. We focused on their antiviral effect, which has not yet been well evaluated.

RESULTS: We compared the anti-influenza viral effects of berries belonging to the genus Vaccinium - 35 species of blueberry (Vaccinium cyanococcus), the Natsuhaze (Vaccinium oldhamii), bilberry (Vaccinium myrtillus) and cranberry (Vaccinium oxycoccos)- with those belonging to the genus Ribes, i.e. blackcurrant (Ribes nigrum). Only Elliott and Legacy among Northern Highbush varieties but many Rabbiteye varieties such as Austin, Baldwin, Brightblue, Festival, T-100 and Tifblue showed anti-influenza viral activity. Natsuhaze, bilberry, cranberry and blackcurrant had high antiviral effects. A relationship was observed between the antiviral effect and total polyphenol content.

CONCLUSIONS: Antiviral effects were found to differ markedly between berry species. Rabbiteye varieties tended to have higher antiviral effects than Northern, Southern and Half Highbush blueberry varieties. We also found that Natsuhaze, which has recently been harvested in Japan as a potential functional food, had an antiviral effect comparable to that of bilberry, cranberry and blackcurrant. There was a positive relationship between antiviral activity and polyphenol content, indicating the possibility that polyphenol is one of the key factors in the antiviral effects of berries. 2012 Society of Chemical Industry.

Cranberries and Their Bioactive Constituents in Human Health

Posted: 
November 14, 2013
Authors: 
Jeffrey B. Blumberg, Terri A. Camesano, Aedin Cassidy, Penny Kris-Etherton, Amy Howell, Claudine Manach, Luisa M. Ostertag, Helmut Sies, Ann Skulas-Ray, and Joseph A. Vita
Journal: 
Adv. Nutr. 4: 618–632, 2013
Abstract: 

Recent observational and clinical studies have raised interest in the
potential health effects of cranberry consumption, an association that
appearsto be due to the phytochemical content of this fruit. The profile of
cranberry bioactives is distinct from that of other berry fruit, being
rich in A-type proanthocyanidins (PACs) in contrast to the B-type PACs present
in most other fruit. Basic research has suggested a number of potential
mechanisms of action of cranberry bioactives, although further molecular
studies are necessary. Human studies on the health effects of cranberry
products have focused principally on urinary tract and cardiovascular
health, with some attention also directed to oral health and
gastrointestinal epithelia. Evidence suggesting that cranberries may decrease the
recurrence of urinary tract infections is important because a nutritional
approach to this condition could lower the use of antibiotic treatment
and the consequent development of resistance to these drugs. There is
encouraging, but limited, evidence of a cardioprotective effect of
cranberries mediated via actions on antioxidant capacity and lipoprotein
profiles. The mixed outcomes from clinical studies with cranberry
products could result from interventions testing a variety of products,
often uncharacterized in their composition of bioactives, using different
doses and regimens, as well as the absence of a biomarker for compliance
to the protocol. Daily consumption of a variety of fruit is necessary to
achieve a healthy dietary pattern, meet recommendations for micronutrient
intake, and promote the intake of a diversity of phytochemicals. Berry
fruit, including cranberries, represent a rich source of phenolic bioactives
that may contribute to human health.

Bioactivities of pilot-scale extracted cranberry juice and pomace.

Posted: 
September 15, 2013
Authors: 
Harrison JE, Oomah BD, Diarra MS, Ibarra-Alvarado C
Journal: 
J Food Process Pres 37(4):356-365
Abstract: 

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.

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.

Cranberries and wild blueberries treated with gastrointestinal enzymes positively modify glutathione mechanisms in Caco-2 cells in vitro

Posted: 
September 15, 2013
Authors: 
Slemmer JE, Livingston-Thomas JM, Gottschall-Pass KT, Sweeney MI
Journal: 
J Food Sci 78(6):H943-7
Abstract: 

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

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 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.

Effects of cranberry components on human aggressive periodontitis gingival fibroblasts.

Posted: 
September 15, 2013
Authors: 
Tipton DA, Babu JP, Dabbous MKh
Journal: 
J Periodontal Res 48(4):433-42
Abstract: 

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 RESULTS: Short-term exposure to NDM, or lipopolysaccharide +/- NDM caused no membrane damage. NDM ( 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.

Evidence that cranberry juice may improve augmentation index in overweight men.

Posted: 
September 15, 2013
Authors: 
Ruel G. Lapointe A. Pomerleau S. Couture P. Lemieux S. Lamarche B. Couillard C.
Journal: 
Nutr Res 33(1):41-9
Abstract: 

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.

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