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.

PURPOSE: We studied the health benefits of low calorie cranberry beverage consumption on glucoregulation, oxidative damage, inflammation, and lipid metabolism in overweight but otherwise healthy humans. METHODS: 78 overweight or obese men and women (30-70 years; BMI 27-35 kg/m2) with abdominal adiposity (waist: hip>0.8 for women and >0.9 for men; waist: height>=0.5) consumed 450 mL placebo or low calorie, high polyphenol cranberry extract beverage (CEB) daily for 8 week in a randomized, double-blind, placebo-controlled, parallel design trial. Blood and urine samples were collected after overnight fast at baseline and after 8 weeks of daily beverage consumption. Blood and urine samples were also collected during 3 oral glucose tolerance test (OGTT) challenges: (1) pre-intervention without the test beverages, (2) following a single dose of placebo or CEB at baseline (week 0), and (3) following a single dose of placebo or CEB at 8 week. RESULTS: Compared to placebo, a single CEB dose at baseline lowered endothelin-1 and elevated nitric oxide and the reduced:oxidized glutathione ratio (P<0.05). Interferon-gamma was elevated (P<0.05) after a single CEB dose at baseline; however, after 8 week of CEB intervention, fasting C-reactive protein was lower (P<0.05). CEB consumption for 8 week also reduced serum insulin and increased HDL cholesterol compared to placebo (P<0.05). CONCLUSIONS: An acute dose of low calorie, high polyphenol cranberry beverage improved antioxidant status, while 8 week daily consumption reduced cardiovascular disease risk factors by improving glucoregulation, downregulating inflammatory biomarkers, and increasing HDL cholesterol.

Background: Interest in using herbal medicines to treat the hypercholesterolemia is increasing. Cranberry extract could decrease plasma cholesterol, however, the active ingredients and the underlying mechanisms remain largely unknown. Hypothesis: The present study was to test the hypothesis that cranberry anthocyanins (CrA) were at least one of the active ingredients responsible for the cholesterol-lowering activity of cranberry fruits via a mechanism of increasing fecal sterol excretion. Methods: Forty-four hamsters were randomly divided into five groups and fed one of the five diets, namely a non-cholesterol control diet (NCD), a high-cholesterol control diet (HCD), a HCD diet supplemented with a low dose of 1% CrA (CL), a HCD diet supplemented with a high dose of 2% CrA (CH), and a HCD diet supplemented with 0.5% cholestyramine as a positive control drug (P-CTL), respectively, for six weeks. Plasma lipoprotein cholesterol was quantified using the enzymatic kits, while the gene expressions of transporters, enzymes and receptors involved in cholesterol absorption and metabolism were quantified using the quantitative RT-PCR. Fecal sterols were quantified using gas chromatography (GC). Results: Plasma total cholesterol and aorta atherosclerotic plaque decreased dose-dependently with the increasing amounts of CrA added into diets. This was accompanied by a dose-dependent increase in excretion of both neutral and acidic sterols. CrA had no effect on the mRNA levels of intestinal Niemann-Pick C1 like 1 protein (NPC1 L1), acyl CoA:cholesterol acyltransferase2 (ACAT2), microsomal triacylglycerol transport protein (MTP), and ATP binding cassette transporter 5 (ABCG5) as well as hepatic cholesterol-7 alpha -hydroxylase (CYP7A1), 3-Hydroxy-3-methylglutaryl reductase (HMG-CoA-R), sterol regulatory element binding protein 2 (SREBP2), LDL receptor (LDL-R), and Liver X receptor alpha (LXR alpha ). Conclusion: CrA as an herbal medicine could favorably modify the lipoprotein profile in hamsters fed a high cholesterol diet by enhancing excretion of fecal neutral and acidic sterols, most likely not mediated by interaction with genes of transporters, enzymes and proteins involved in cholesterol absorption and metabolism