Lipid metabolism and inflammation contribute to CVD development. This study investigated whether the consumption of cranberries (CR; Vaccinium macrocarpon) can alter HDL metabolism and prevent inflammation in mice expressing human apo A-I transgene (hApoAITg), which have similar HDL profiles to those of humans. Male hApoAITg mice were fed a modified American Institute of Nutrition-93M high-fat/high-cholesterol diet (16 % fat, 0.25 % cholesterol, w/w; n 15) or the high-fat/high-cholesterol diet containing CR (5 % dried CR powder, w/w, n 16) for 8 weeks. There were no significant differences in body weight between the groups. Serum total cholesterol, non-HDL-cholesterol and TAG concentrations were significantly lower in the control than CR group with no significant differences in serum HDL-cholesterol and apoA-I. Mice fed CR showed significantly lower serum lecithin-cholesterol acyltransferase activity than the control. Liver weight and steatosis were not significantly different between the groups, but hepatic expression of genes involved in cholesterol metabolism was significantly lower in the CR group. In the epididymal white adipose tissue (eWAT), the CR group showed higher weights with decreased expression of genes for lipogenesis and fatty acid oxidation. The mRNA abundance of F4/80, a macrophage marker and the numbers of crown-like structures were less in the CR group. In the soleus muscle, the CR group also demonstrated higher expression of genes for fatty acid beta-oxidation and mitochondrial biogenesis than those of the control. In conclusion, although CR consumption elicited minor effects on HDL metabolism, it prevented obesity-induced inflammation in eWAT with concomitant alterations in soleus muscle energy metabolism.

Cranberry volatiles have received little attention for health-promoting properties. In this study, we compared the inhibitory effects of cranberry polyphenol and volatile extracts and volatile standards on nitric oxide (NO) production in lipopolysaccharide (LPS) activated RAW 264.7 macrophages. Polyphenols were analyzed by HPLC/HPLC-MS and volatiles were analyzed by GC/GC-MS. The inhibition of NO production of the fresh cranberry polyphenol and volatile extracts and alpha -terpineol, linalool, linalool oxide, and eucalyptol standards at 2, 4, and 8-fold dilutions of their original concentrations in fresh cranberries was evaluated by treating these extracts/standards for 1 h before or after LPS application for 24 h. After inducing inflammation with LPS, the polyphenol treatments (317.8 and 635.7 micro g g-1) and 1.8 micro g g-1 volatile treatment lowered NO levels 46-62% compared to the positive control (P<0.05). When the cells were treated with polyphenol and volatile extracts before inducing inflammation, the 635.7 micro g g-1 and 317.8 micro g g-1 polyphenol treatments and 1.8 micro g g-1 and 0.9 micro g g-1 volatile treatments lowered NO levels (13-52%) compared to the positive control (P<0.05). Polyphenol and volatile extracts from cranberry were effective in reducing NO production whether applied before or after the application of LPS. alpha -Terpineol at a concentration found in fresh cranberries (1.16 micro g mL-1) was also found to be effective in reducing NO production whether cells were treated before or after application of LPS. Future studies are needed to reveal the mechanisms by which volatile compounds, especially alpha -terpineol act to mitigate inflammation and to determine the bioavailability of terpenes.

The present study is designed to investigate the role of certain natural cranberry and rosemary extracts to improve the histological changes in the cardiac muscle toxicity of adult male albino rats weighing 110±5g (aged 3-4 weeks) induced by doxorubicin (DOX). To assessment of cardiotoxicity, the cardiac enzyme creatine kinase (CK-MB) and troponin I protein were measured. The animals were divided into 7 equal groups (10 rats /each); Gp. I: normal control rats group injected with saline solution 0.9 % intraperitoneally (i.p.) for three times per a week for three weeks, Gp. II: cranberry rats group administrated orally with 150 mg/kg/bw for three times per a week for three weeks, Gp III rosemary rats group administrated orally with 2g/kg/bw for three times per a week for three weeks, Gp IV: DOX rats group injected i.p. with 2.5mg/kg three times / week for two weeks, Gps: V, VI & VII: DOX rat groups administrated orally with cranberry or rosemary or both together in the same previous doses and duration. In the present research, the measurement of CK - MB enzyme and troponin I protein are recorded high values in the blood sera in DOX -rats group (Gp IV) in comparison with other control groups (Gps. I, II& III) and treated groups (Gps; V, VI & VII) in which the levels of CK-MP and troponin I are recorded approximately normal values as in control group (Gp. I). Histological study of the cardiac muscle of normal control rats group (Gp.I) revealed normal branched cardiomyocytes with normal striations and normal oval centrally located nuclei. Similar observations are seen in the cranberry and rosemary rat groups (Gps. II& III). In DOX rats group (Gp IV), the histological observations of the cardiac muscle demonstrated many alternations such as disarrangement, degeneration and vacuolation of the cardiomyocytes. The appearance of infiltration of inflammatory cells and necrotic areas in most cardiomyocytes as well as dilation and congestion of blood vessels in the dilated endomysia were also observed. The administration of either cranberry alone or cranberry with rosemary together to DOX rats group revealed an obvious improvement and harmony restoration of the histological structure with normal appearance of the cardiomyocytes with normal oval nuclei, and complete disappearance of dilated and congested blood vessels, more than those given rosemary only. In brief, DOX rats group given either cranberry alone or cranberry with rosemary together recorded marked recovery of the normal values of CK-MB and troponin I as well as the restoration of the architecture of the cardiac muscle to approximately normal form than those given rosemary only.

Alcoholic steatohepatitis is an important medical problem but its effective therapies are still not available. Plant polyphenols are widely used for prevention of toxic liver damages. The aim of the study was to evaluate the hepatoprotective mechanism(s) of a cranberry peel polyphenol-rich extract, focusing on the effects of the polyphenols on the mitochondrial function.The main components of cranberry peel phenolic compounds were anthocyanins, flavan-3-ols, procyanidins, flavonols, phenolic acids, as was detected using UHPLC-ESI-QTOF-MS. The treatment of rats receiving ethanol (4 g/kg bw, 8 weeks) with cranberry polyphenols (daily, 4 mg/kg bw) partially prevented alcoholic liver damage, ameliorating steatosis and inflammatory signs in the liver, decreasing serum and liver triglyceride contents, ALT and AST activities, as well as diminishing TNFα and TGFβ levels in serum. The polyphenols inhibited Ca2+ - induced mitochondrial permeability transition, free radical generation in mitochondria during intoxication. The polyphenols (25 µg/ml) prevented mitochondrial oxidative impairments in vitro. In conclusion, the cranberry peel polyphenols with antioxidant properties exerted a hepatoprotective and anti-inflammatory effects in the model of alcoholic steatohepatitis via prevention of liver mitochondria dysfunction.

Cranberry ( Vaccinium macrocarpon) products are widely available in North American food, juice, and dietary supplement markets. The use of cranberry is popular for the prevention of urinary tract infections (UTIs) and other reported health benefits. Preliminary findings by our research group indicate that arabinoxyloglucan oligosaccharides are present in cranberry products and may contribute to the antiadhesion properties of urine produced after cranberry consumption, but relatively little is known regarding the oligosaccharide components of cranberry. This report describes the isolation from two cranberry sources and the complete structure elucidation of two arabinoxyloglucan oligosaccharides through the use of carbohydrate-specific NMR spectroscopic and chemical derivatization methods. These compounds were identified as the heptasaccharide beta-d-glucopyranosyl-(1->4)-[alpha-d-xylopyranosyl-(1->6)]-beta-d-glucopyranosyl-(1->4)-beta-d-glucopyranosyl-(1->4)-[alpha-l-arabinofuranosyl-(1->2)-alpha-d-xylopyranosyl-(1->6)]-beta-d-glucopyranose (1) and the octasaccharide beta-d-glucopyranosyl-(1->4)-[alpha-l-arabinofuranosyl-(1->2)-alpha-d-xylopyranosyl-(1->6)]-beta-d-glucopyranosyl-(1->4)-beta-d-glucopyranosyl-(1->4)-[alpha-l-arabinofuranosyl-(1->2)-alpha-d-xylopyranosyl-(1->6)]-beta-d-glucopyranose (2). Selected fractions and the isolated compounds were subjected to antimicrobial, cell viability, and E. coli antiadhesion assays. Results indicated that enriched fractions and purified compounds lacked antimicrobial and cytotoxic effects, supporting the potential use of such compounds for disease prevention without the risk for resistance development. Preliminary antiadhesion results indicated that mixtures of oligosaccharides exhibited greater antiadhesion properties than purified fractions or pure compounds. The potential use of cranberry oligosaccharides for the prevention of UTIs warrants continued investigations of this complex compound series.

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; 70 mg/kg i.p.) for 8 weeks day after day and treated with CRAN (100 mg/kg b.wt.) orally daily for 4 weeks started after 4 weeks from AlCl3 injection accompanied with an administration of LOS (5 mg/kg i.p.) three times weekly for 4 weeks. 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.

BACKGROUND & AIMS: The impetus for the current study was to evaluate the efficacy of cranberry supplementation on cardiovascular disease metabolic risk factors in adult populations.METHODS: A systematic review was conducted on PubMed, Scopus, Web of Science and Google Scholar up to June 2018, to identify randomized controlled trials investigating the effect of cranberry supplementation on cardiovascular metabolic risk factors.RESULTS: The results of the pooled effect size indicated that cranberry administration significantly reduced systolic blood pressure and body mass index. No statistically significant change was observed in triacylglycerol, total cholesterol, low-density lipoprotein, high-density lipoprotein, fasting plasma glucose, fasting insulin, homeostasis model assessment of insulin resistance, diastolic blood pressure, waist circumference, C-reactive protein, and intercellular adhesion molecule. Stratified analysis showed that SBP reduction was more pronounced in studies with >=50 mean age participants. Also, subgroup analysis suggested a significant increase in high-density lipoprotein concentrations in subgroups with subjects <50 mean age, and triacylglycerol levels in subsets with cranberry administered in juice form.CONCLUSIONS: This systematic review and meta-analysis suggests cranberry supplementation may be effective in managing systolic blood pressure, body mass index and high-density lipoprotein in younger adults. Further high-quality studies are needed to confirm these results.

The main goal of this work was to clarify the effects of the consumption of berries on cardiovascular disease (CVD) risk factors by performing a systematic review according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) statement, followed by a meta-analysis and a trial sequential analysis (TSA) of randomized controlled trials (RCTs). The electronic search was conducted in PubMed, Scopus, SciELO, Web of Science and Cochrane Library between April and June 2016. To be included, RCTs had to report 1 or more of the following outcomes: total cholesterol (TC), HDL-cholesterol (HDL), LDL-cholesterol (LDL), triglycerides (TG), blood pressure (BP), C-reactive protein (CRP), tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), vascular cell adhesion molecule-1 (VCAM), intercellular adhesion molecule-1 (ICAM), glucose, insulin, apolipoprotein A-I (Apo A-I) or apolipoprotein B (Apo B). It was observed that the intake of berries reduces TC, LDL, TG, and BP while increasing the level of HDL, suggesting a beneficial effect on the control of CVDs' risk factors. Thus, the intake of berries as nutraceuticals or functional foods could be suggested for the prevention and control of CVDs.

OBJECTIVES:Studies have shown that cranberry (Vaccinium macrocarpon) has antiinflammatory and antioxidant effects; however, to our knowledge, the effects of cranberry juice consumption have not been studied in patients with rheumatoid arthritis (RA). The aim of this study was to verify the effect of cranberry juice consumption on several inflammatory biomarkers and on the disease activity of patients with RA.METHODS:A prospective study was conducted with 41 women diagnosed with RA. The disease activity measured by Disease Activity Score 28 (DAS28) and anticyclic citrullinated peptide (anti-CCP) antibodies, and several inflammatory and biochemical biomarkers were analyzed. The control group (n = 18) maintained their usual diet. The cranberry group (n = 23) consumed 500 mL/d of low-calorie cranberry juice.RESULTS:Regarding the baseline values, the cranberry group presented a decrease in the values of DAS28 (P = 0.048) and anti-CCP (P = 0.034) after 90 d of treatment, whereas changes in inflammatory biomarkers were not found.CONCLUSION:The present study indicated that cranberry juice decreases disease activity and therefore has beneficial effects for RA patients, although larger and long-term studies are needed to definitively probe this effect and to clarify the mechanisms involved.

To study the anti-inflammatory effect of cranberry extract on inflammation suppression induced by lipopolysaccharide, and explore its mechanism. Cell inflammatory model was established with RAW264.7 cells treated with lipopolysaccharide. Cell viability of RAW264.7 cells treated with cranberry extract were analyzed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The effect of cranberry extract on nucleus was observed by 4',6-diamidino-2-phenylindole(DAPI)staining. The activity of nitric oxide synthase (NOS) was determined by fluorescence analysis. Enzyme-linked immunosorbent assay (ELISA) for determination of IL-1 beta , IL-6 and TNF- alpha . RAW264.7 cells were treated with cranberry extract for 24 h, and the expression of Keap1, Nrf2, HO-1, IKK alpha / beta and NF- kappa Bp65 were detected by Western blotting. The result showed that the inflammatory model was established by 5 micro g/mL lipopolysaccharide, the highest level of inflammation was reached at 24 hours. There was no significant toxic effect on RAW246.7 cells in the range of 5 micro g/mL-400 micro g/mL, and the cell nucleus was intact and without obvious damage. Compared with the model group, cranberry extract could significantly inhibit the activity of NOS and decreased the content of IL-1 beta , IL-6, TNF- alpha with the increase of dose. The Western blot result showed that cranberry extract inhibited the expression of Keap1, IKK alpha / beta , NF- kappa Bp65 and increase the expression of Nrf2 and HO-1 protein levels. These results suggest that cranberry extract can inhibit the inflammatory response induced by lipopolysaccharide, and its mechanism may be related to activation of Keap1/Nrf2/HO-1 signaling pathway and NF- kappa Bp65.