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Cranberry (Vaccinium Macrocarpon) Peel Polyphenol-Rich Extract Attenuates Rat Liver Mitochondria Impairments in Alcoholic Steatohepatitis in Vivo and After Oxidative Treatment in Vitro

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Authors
Zavodnikab I, Bukobc V, Lukivskayab O, Lapshinaa E, Ilyicha T, Belonovskayab E, Kirkob S, Narutab E, Kuzmitskayab I, Budrynd G, Zyzeleviczd D, Orachd J, Zakrzeskac A, Kiryukhinaa L.
Journal
Journal of Functional Foods. 57:83-94.
Abstract

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 Attenuates Progression of Non-alcoholic Fatty Liver Disease Induced by High-Fat Diet in Mice.

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Authors
Shimizu K; Ono M; Imoto A; Nagayama H; Tetsumura N; Terada T; Tomita K; Nishinaka T.
Journal
Biological & Pharmaceutical Bulletin. 42(8):1295-1302
Abstract

Obesity is characterized by abnormal or excessive fat accumulation, which leads to the development of metabolic syndrome. Because oxidative stress is increased in obesity, antioxidants are regarded as suitable agents for preventing metabolic syndrome. Here, we examined the impact of cranberry, which contains various antioxidants, on metabolic profiles, including that during the progression of non-alcoholic fatty liver disease (NAFLD), in high-fat diet (HFD)-fed C57BL/6 mice. We observed that oxidative stress was diminished in mice that were fed HFD diets supplemented with 1 and 5% cranberry powder as compared with that in HFD-fed control mice. Notably, from 1 week after beginning the diets to the end of the study, the body weight of mice in the cranberry-treatment groups was significantly lower than that of mice in the HFD-fed control group; during the early treatment phase, cranberry suppressed the elevation of serum triglycerides; and adipocytes in the adipose tissues of cranberry-supplemented-HFD-fed mice were smaller than these cells in HFD-fed control mice. Lastly, we examined the effect of cranberry on NAFLD, which is one of the manifestations of metabolic syndrome in the liver. Histological analysis of the liver revealed that lipid-droplet formation and hepatocyte ballooning, which are key NAFLD characteristics, were both drastically decreased in cranberry-supplemented-HFD-fed mice relative to the levels in HFD-fed control mice. Our results suggest that cranberry ameliorates HFD-induced metabolic disturbances, particularly during the early treatment stage, and exhibits considerable potential for preventing the progression of NAFLD.

Cranberry Extract with Enhanced Bactericidal Activities Against Uropathogenic Escherichia Coli within one Minute of Treatment

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Authors
Kim SA, Kim HW, Rhee MS
Journal
LWT 113:108318, https://doi.org/10.1016/j.lwt.2019.108318
Abstract

Cranberry has been widely utilized as a popular botanical dietary supplement to prevent urinary tract infection. The study aims to evaluate the enhanced bactericidal activities of cranberry against uropathogenic Escherichia coli (UPEC) by adding a small quantity of naturally derived antimicrobials. The antibacterial effect was examined with cranberry extract alone (15 and 20%), three kinds of medium-chain fatty acids alone (caprylic, capric, and lauric acid; 0.05–1.0 mM), essential oils alone (carvacrol and thymol; 0.5–1.0 mM), and cranberry extract containing medium-chain fatty acids or essential oils at 37 °C for 1 min. The survivors were remarkably reduced with cranberry extract containing any of the antimicrobials. For example, cranberry extract (15 and 20%) with 1.0 mM of each caprylic acid, lauric acid, and carvacrol resulted in the complete eradication of UPEC (7.55 log reduction). Flow cytometry analysis of UPEC cells exposed to combined treatment showed clear membrane disruption and cell death (>95% of damage). Adding antimicrobials to cranberry extract did not affect (P > 0.05) the characteristics of the cranberry extract (Color, °Brix, pH). The present method may be more acceptable to consumers, who tend to avoid products containing synthetic chemicals and prefer the use of natural agents.

Cranberry Polyphenols: Natural Weapons Against Dental Caries.

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Authors
Philip N; Walsh LJ.
Journal
Dentistry Journal. 7(1)
Abstract

Bioactive polyphenol components of cranberry (Vaccinium macrocarpon) are known to have virulence attenuating effects against several cariogenic virulence properties responsible for dental caries pathogenesis. In particular, cranberry A-type proanthocyanidins and flavonols have demonstrated potent inhibitory effects against cariogenic virulence targets such as bacterial acidogenicity, aciduricity, glucan synthesis, and hydrophobicity. Cranberry phenols have the ability to disrupt these cariogenic virulence properties without being bactericidal, a key quality essential for retaining the benefits of the symbiotic resident oral microbiome and preventing the emergence of resistant microbes. This review discusses the cariostatic mechanisms of specific cranberry phytochemicals and their potential use as therapeutic agents against cariogenic bacteria in the prevention and control of dental caries.

Development of a Cranberry Standard for Quantification of Insoluble Cranberry (Vaccinium macrocarpon Ait.) Proanthocyanidins.

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Authors
Gullickson ER; Krueger CG; Birmingham A; Maranan M; Reed JD.
Journal
Journal of Agricultural & Food Chemistry 10.1021/acs.jafc.9b03696 [doi]
Abstract

Cranberry proanthocyanidins (PACs) can be partitioned into soluble PACs, which are extracted with solvents, and insoluble PACs, which remain associated with fibers and proteins after extraction. Most research on cranberry products only quantifies soluble PACs because proper standards for quantifying insoluble PACs are lacking. In this study, we evaluated the ability of a cranberry PAC (c-PAC) standard, reflective of the structural heterogeneity of PACs found in cranberry fruit, to quantify insoluble PACs by the butanol-hydrochloric acid (BuOH-HCl) method. For the first time, a c-PAC standard enabled conversion of BuOH-HCl absorbance values (550 nm) to a weight (milligram) basis, allowing for quantification of insoluble PACs in cranberries. The use of the c-PAC reference standard for sequential analysis of soluble PACs by the method of 4-(dimethylamino)cinnamaldehyde and insoluble PACs by the method of BuOH-HCl provides analytical tools for the standardization of cranberry-based ingredients.

Effect of Polyphenol-Rich Cranberry Extracts on Cariogenic Biofilm Properties and Microbial Composition of Polymicrobial Biofilms.

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Authors
Philip N; Bandara HMHN; Leishman SJ; Walsh LJ.
Journal
Archives of Oral Biology. 102:1-6
Abstract

OBJECTIVE: To investigate the effect of cranberry extracts on saliva-derived polymicrobial biofilms with regards to biofilm biomass, acidogenicity, exopolysaccharide (EPS)/microbial biovolumes, colony forming unit (CFU) counts, and the relative abundance of specific caries- and health-associated bacteria.METHODS: Saliva-derived polymicrobial biofilms were grown for 96 h in a cariogenic environment and treated for 2 min every 12 h over the entire biofilm growth period with 500 mug/mL cranberry extract or vehicle control. The effect of the cranberry extract on biofilm behaviour was evaluated using different assays and its influence on key cariogenic and health-associated bacterial populations was assessed with a microarray real-time quantitative PCR method.RESULTS: Cranberry-treated biofilms showed significant drops in biomass (38% reduction, P < 0.001), acidogenicity (44% reduction, P < 0.001), EPS/microbial biovolume ratios (P = 0.033), and CFU counts (51% reduction, P = 0.001). Furthermore, the cranberry extracts effected a significantly lower relative abundance of caries-associated Streptococcus sobrinus (fold change 0.004, P = 0.002) and Provotella denticola (0.002, P < 0.001), and a significantly higher relative abundance of the health-associated Streptococcus sanguinis (fold change 90.715, P = 0.001).CONCLUSIONS: The cranberry extract lowered biofilm biomass, acidogenicity, EPS/microbial biovolumes, CFU counts, and modulated a beneficial microbial ecological change in saliva-derived polymicrobial biofilms.

Effects of Blueberry and Cranberry Consumption on Type 2 Diabetes Glycemic Control: A Systematic Review.

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Authors
Rocha DMUP; Caldas APS; da Silva BP; Hermsdorff HHM; Alfenas RCG.
Journal
Critical Reviews in Food Science & Nutrition. 59(11):1816-1828
Abstract

The metabolic effects of cranberry and blueberry consumption on glycemic control have been evaluated in vitro and in animal models as well as in human studies, although findings have not been systematically reviewed yet. Therefore, a systematic review was carried out of relevant randomized clinical trials (RCTs) in order to assess the effect of berries (blueberry and cranberry) consumption on type 2 diabetes (T2DM) glycemic control. Some evidences were also discussed on the anti-diabetic mechanisms exerted by berries polyphenols. Studies were identified by searching electronic databases: LILACS, PubMed/MEDLINE, Scopus, The Cochrane Library and Web of Science. Three authors independently searched and extracted RCTs in which the effect of berries (cranberry or blueberry) consumption on T2DM glycemic control was assessed. A total of 7 RCTs, involving 270 adults with type 2 diabetes were included. Despite the heterogeneity of the administration forms (in natura, dried, extract, preparations - juice), dosage, duration of the intervention and type of population of the studies involving these two berries some studies highlight the potential benefit of berries, especially of blueberry, on glucose metabolism in T2DM subjects. Daily cranberry juice (240 mL) consumption for 12 weeks and blueberry extract or powder supplementation (9.1 to 9.8 mg of anthocyanins, respectively) for 8 to 12 weeks showed a beneficial effect on glucose control in T2DM subjects. Those results indicate a promising use of these berries in T2DM management; although more studies are required to better understand the mechanisms involved.

Evaluation of the Degree of Polymerization of the Proanthocyanidins in Cranberry by Molecular Sieving and Characterization of the Low Molecular Weight Fractions by UHPLC-Orbitrap Mass Spectrometry.

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Authors
Gardana, C. Simonetti, P.
Journal
Molecules. 24(8):1504
Abstract

4-dimethylammino-cinnamaldehyde (DMAC) assays quantify total proanthocyanidins (PACs) but do not provide qualitative PAC molecular weight distribution information and cannot discriminate between A- and B-type PACs. We developed an efficient method for assessing PAC molecular weight distributions. The PACs from three commercial cranberry extracts (A1-A3) were fractionated by molecular sieves with cut-offs of 3, 10, 30, 50, and 100 kDa, and each fraction was analyzed by DMAC assays. A1, A2, and A3 contained 27%, 33%, and 15% PACs, respectively. Approximately 28 PACs, 20 flavonols, and 15 phenolic acids were identified by UHPLC-DAD-Orbitrap MS in A1 and A3, while A2 contained only flavan-3-ols. Epicatechin was the main monomer in A1 and A3, and catechin was the main in A2. Procyanidin A2 was the main dimer in A1 and A3, representing more than 85% of the total dimers, while it constituted approximately only 24% of A2. A1 and A3 contained quercetin, isorhamnetin, myricetin, and their glycosides, which were totally absent in A2. In A1 and A3 the PACs were mainly distributed in the fractions 30-3 and <3 kDa, while in A2 more than 70% were present in the fraction less than 3 kDa. Overall, obtained data strongly suggests that A2 is not cranberry-derived, or is adulterated with another source of PACs.

Glycaemic Regulation, Appetite and Ex Vivo Oxidative Stress in Young Adults Following Consumption of High-Carbohydrate Cereal Bars Fortified with Polyphenol-Rich Berries.

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Authors
Smith TJ; Karl JP; Wilson MA; Whitney CC; Barrett A; Farhadi NF; Chen CO; Montain SJ.
Journal
British Journal of Nutrition. 121(9):1026-1038
Abstract

Consumption of certain berries appears to slow postprandial glucose absorption, attributable to polyphenols, which may benefit exercise and cognition, reduce appetite and/or oxidative stress. This randomised, crossover, placebo-controlled study determined whether polyphenol-rich fruits added to carbohydrate-based foods produce a dose-dependent moderation of postprandial glycaemic, glucoregulatory hormone, appetite and ex vivo oxidative stress responses. Twenty participants (eighteen males/two females; 24 (sd 5) years; BMI: 27 (sd 3) kg/m2) consumed one of five cereal bars (approximately 88 % carbohydrate) containing no fruit ingredients (reference), freeze-dried black raspberries (10 or 20 % total weight; LOW-Rasp and HIGH-Rasp, respectively) and cranberry extract (0.5 or 1 % total weight; LOW-Cran and HIGH-Cran), on trials separated by >=5 d. Postprandial peak/nadir from baseline (DELTAmax) and incremental postprandial AUC over 60 and 180 min for glucose and other biochemistries were measured to examine the dose-dependent effects. Glucose AUC0-180 min trended towards being higher (43 %) after HIGH-Rasp v. LOW-Rasp (P=0.06), with no glucose differences between the raspberry and reference bars. Relative to reference, HIGH-Rasp resulted in a 17 % lower DELTAmax insulin, 3 % lower C-peptide (AUC0-60 min and 3 % lower glucose-dependent insulinotropic polypeptide (AUC0-180 min) P<0.05. No treatment effects were observed for the cranberry bars regarding glucose and glucoregulatory hormones, nor were there any treatment effects for either berry type regarding ex vivo oxidation, appetite-mediating hormones or appetite. Fortification with freeze-dried black raspberries (approximately 25 g, containing 1.2 g of polyphenols) seems to slightly improve the glucoregulatory hormone and glycaemic responses to a high-carbohydrate food item in young adults but did not affect appetite or oxidative stress responses at doses or with methods studied herein.

Inhibitory Effects of Lingonberry Extract on Oral Streptococcal Biofilm Formation and Bioactivity.

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Authors
Kokubu E; Kinoshita E; Ishihara K.
Journal
Bulletin of Tokyo Dental College. 60(1):1-9, 2019
Abstract

Phenolic compounds in fruits such as cranberries have been shown to promote a number of biological activities. The purpose of this study was to investigate the effects of polyphenolic compound-containing lingonberry extract on oral streptococci and compare them with the known anti-cariogenic activity of cranberries. Water-soluble and polyphenol-rich fractions (Fractions I and II, respectively) were isolated from cranberries and lingonberries. The effects of those fractions on the biofilm formation ability and bioactivity of Streptococcus mutans MT8148R, Streptococcus sobrinus 6715, and Streptococcus sanguinis ATCC 10556 were then evaluated. Cranberry or lingonberry Fraction II (at 0.5-1 mg/ml) significantly reduced biofilm formation by S. mutans, S. sobrinus, and S. sanguinis. In contrast, cranberry or lingonberry Fraction I (at 0.5-2 mg/ml) increased biofilm formation by S. mutans and S. sobrinus, but not by S. sanguinis. Fractions I and II (at 1-2 mg/ml) also reduced the bioactivity of S. mutans, while Fraction II (at 0.5 mg/ml) enhanced the bioactivity of all tested strains. The results revealed that lingonberries contained a larger amount of polyphenol than cranberries and that they showed almost the same level of activity against the biofilm formation ability and bioactivity of oral streptococci. This indicates that polyphenol-rich lingonberry fraction offers a promising natural food derivative for prevention of dental caries.