Epigallocatechin gallate (EGCG) of green tea and the nutraceutical CystiCran-40 (containing 40% proanthocyanidins) of the cranberry plant have been associated with antiviral activity. The purpose of this work was to determine the mechanism of antiviral synergy between each compound. Coliphage T4II (phage T4) and the rotavirus strain SA-11(RTV) were used as model virus systems. Individual and combined flavonoids structural and molecular weight analyses were performed by NMR and HPCL/MS, respectively. A suboptimal concentration of EGCG or C-40 alone or in combination reduced phage infectivity by <=10%. Similarly, EGCG (30 micro g/ml) and C-40 (25 micro g/ml), respectively, reduced RTV titers by 3 and 13%. However, RTV titers were reduced by 32% (p < .05) with both flavonoids used in combination. RTV was not recognized in host cells by electron microscopy 24-h post-inoculation. NMR and HPLC/MS findings revealed significant structural and potential changes in molecular weight of the flavonoids in complex.

INTRODUCTION: Hyperlipidemia, obesity, hypertension, and diabetes are the most important risk factors for cardiovascular diseases. The aim of this systematic review article is to introduce the medicinal plants that exert significant clinical effects on hypertension, hyperlipidemia, obesity, and diabetes. METHODS: In this review article, the international research databases including MEDLINE, Google scholar, EBSCO, Academic Search, Web of Science, SciVerse, Scopus (SCOPUS), EBSCO, Academic Search, Cochrane, Central Register of Controlled Trials (CENTRAL) and a Chinese database (China Network Knowledge Infrastructure [CNKI]) were searched using the key words hyperlipidemia, hypertension, diabetes, herbal, obesity, and phytomedicine, matched by MESH, from their respective inceptions up to March, 2016. The plants that were effective on one, two, three, or all of four diseases were determined. The doses, side effects, the most important pharmaceutically effective compounds, the used organs, and important points regarding usage were separately recorded. Also known clinically significant interactions were presented. RESULTS: 1023 articles were found to be about medicinal plants and hypertension, 1912 articles about medicinal plants and hyperlipidemia, 810 articles about medicinal plants and obesity, 1174 articles about medicinal plants and diabetes. Of 144 plants included in the analysis, 83 were found to be effective on hyperlipidemia, 100 on hypertension, 66 on obesity, and 72 on diabetes. 43 plants were found to be effective on two diseases, 14 on three diseases, and 34 on all four diseases. Three plants (Tomato, Cranberry and Pomegranate), in food and therapeutic doses, were found to be used to treat cardiovascular diseases especially in pre-eclampsia and hyperlipidemia in pregnancy. CONCLUSION: Regarding the findings of this study, we can argue that the medicinal plants, other than monotherapy, can be used as poly-therapy, to treat cardiovascular diseases.

Cranberries and cranberry-derived diet supplements are often recommended for the treatment of urinary tract infections, also during pregnancy. These products contain strongly anti-angiogenic chemical compounds which could not be indifferent to the developing fetus. In the present work we evaluated the effect of feeding pregnant and lactating mice American cranberry extract (daily dose 0.88 mg) on the morphology and some parameters of spleen and kidney function of their adult progeny. Six weeks after delivery the morphometry of spleen and kidney, cytometric analysis of spleen lymphocytes, evaluation of humoral response to SRBC (Sheep Red Blood Cells), and examination of serum creatinine/urea concentration, were performed in the offspring. Spleens of progeny from experimental (E) group differed from the spleens of progeny of control mice in the lower number of lymphatic nodules and their larger diameter. Cytometry of spleen cells from progeny of E mothers revealed more CD19+ and CD8+ lymphocytes than in the control group. No difference was seen in the response to immunization by red blood cells of sheep (SRBC) between control and E offspring. An increase in the diameter of glomeruli was observed in the kidneys of the experimental group in comparison with the control group. No abnormalities in creatinine and urea serum level were observed. A higher concentration of VEGF and bFGF in E offspring sera in comparison to the controls was seen. CONCLUSION: Although the observed differences between the control and experimental group were not large, caution is recommended in using cranberries and their extracts during pregnancy until more research will be done on this topic.

BACKGROUND: A diet rich in fruit, vegetables and juices is associated with health benefit and reduced risk of certain civilization diseases. Antioxidant properties depend mainly on the total content of polyphenols and their composition. The aim of this study was to perform a multidimensional comparative analysis of phenolic compounds of organic juices with high antioxidant capacity (chokeberry, elderberry, cranberry, pomegranate).RESULTS: All the analyzed juices were a rich source of phenolic compounds. Chokeberry juices had the highest total polyphenol content (up to 7900 mg GAE L-1 ). These juices as well as pomegranate juice were characterized by the highest antioxidant capacity (~5000 mg Trolox equivalents L-1 ). Other samples had lower total polyphenols content and total antioxidant capacity. Multidimensional analysis of the profiles of phenolic compounds showed that chokeberry juices differ from the other juices. Cranberry and pomegranate juices were similar to each other, and elderberry juice was closer to these samples than to chokeberry. The predominant polyphenols of chokeberry juices were anthocyanins (especially cyanidin-3-galactoside and cyanidin-3-arabinoside) and phenolic acids (chlorogenic and neochlorogenic acid). Elderberry juice was an exception by having flavonols (quercetin derivatives) as the principal compounds.CONCLUSION: Chokeberry juices were characterized by the highest antioxidant properties, which predispose them to further clinical research concerning the supporting cardiovascular disease prophylaxis

1. The aim of this study was to evaluate the role of intestinal esterases on the absorption process of tenofovir disoproxil fumarate (TDF). 2. The esterase inhibition capacity of fruit juices (FJs) rich in ester linkages and pharmaceutical excipients (having ester bonds) was performed in vitro by incubating TDF with each FJ and excipient in the intestinal washings. The ex vivo everted gut sac model was also used to evaluate the absorption enhancement capacity of these FJs and excipients. Single-dose oral pharmacokinetic studies were performed by concomitant administration of TDF with each of the selected FJs and excipients. 3. The in vitro and ex vivo studies showed that cremophor-EL and all FJs prevented the metabolism of TDF with grapefruit juice (GFJ) having the highest level of inhibition. Further, the permeability flux of the monoester form of tenofovir was increased by 113% and 212% by cranberry juice (CBJ) and GFJ, respectively. The in vivo studies also showed that both CBJ and GFJ enhanced the oral bioavailability of TDF as the AUC was increased by 24% and 97%, respectively. 4. These results indicate that the prevention of the metabolic conversion of TDF to its monoester form is crucial in increasing the oral absorption of TDF.

CONTEXT:Cranberry has numerous biological activities, including antioxidation, anticancer, cardioprotection, as well as treatment of urinary tract infection (UTI), attributed to abundant phenolic contents.OBJECTIVE:The current study focused on the effect of cranberry juice (CJ) on blue light exposed human retinal pigment epithelial (ARPE-19) cells which mimic age-related macular degeneration (AMD).MATERIALS AND METHODS:Preliminary phytochemical and HPLC analysis, as well as total antioxidant capacity and scavenging activity of cranberry ethyl acetate extract and different CJ fractions (condensed tannins containing fraction), were evaluated. In cell line model, ARPE-19 were irradiated with blue light at 450 nm wavelength for 10 h (mimic AMD) and treated with different fractions of CJ extract at different doses (5-50 μg/mL) by assessing the cell viability or proliferation rate using MTT assay (repairing efficacy).RESULTS:Phytochemical and HPLC analysis reveals the presence of several phenolic compounds (flavonoids, proanthocyanidin, quercetin) in ethyl acetate extract and different fractions of CJ. However, the condensed tannin containing fraction of ethyl acetate extract of CJ displayed the greater (p < 0.05) scavenging activity especially at the dose of 1 mg/mL. Similarly, the condensed tannin containing fraction at 50 μg/mL presented better (p < 0.05) repairing ability (increased cell viability). Furthermore, the oligomeric condensed tannin containing fraction display the best (p < 0.05) repairing efficiency at 50 μg/mL.DISCUSSION AND CONCLUSION:In conclusion, this study distinctly proved that condensed tannin containing fraction of CJ probably exhibits better free radicals scavenging activity and thereby effectively protected the ARPE-19 cells and thus, hampers the progress of AMD.

Wheat allergy is an IgE-mediated disorder. Polyphenols, which are known to interact with certain proteins, could be used to reduce allergic reactions. This study screened several polyphenol sources for their ability to interact with gliadins, mask epitopes, and affect basophil degranulation. Polyphenol extracts from artichoke leaves, cranberries, apples, and green tea leaves were examined. Of these extracts, the first three formed insoluble complexes with gliadins. Only the cranberry and apple extracts masked epitopes in dot blot assays using anti-gliadin IgG and IgE antibodies from patients with wheat allergies. The cranberry and artichoke extracts limited cellular degranulation by reducing mouse anti-gliadin IgE recognition. In conclusion, the cranberry extract is the most effective polyphenol source at reducing the immunogenicity and allergenicity of wheat gliadins.

Peanut allergy is a worldwide health concern. In this study, the natural binding properties of plant-derived polyphenols to proteins was leveraged to produce stable protein-polyphenol complexes comprised of peanut proteins and cranberry (Vaccinium macrocarpon Ait.) or lowbush blueberry (Vaccinium angustifolium Ait.) pomace polyphenols. Protein-bound and free polyphenols were characterized and quantified by multistep extraction of polyphenols from protein-polyphenol complexes. Immunoblotting was performed with peanut-allergic plasma to determine peanut protein-specific IgE binding to unmodified peanut protein, or to peanut protein-polyphenol complexes. In an allergen model system, RBL-2H3 mast cells were exposed to peanut protein-polyphenol complexes and evaluated for their inhibitory activity on ionomycin-induced degranulation ( beta -hexosaminidase and histamine). Among the evaluated polyphenolic compounds from protein-polyphenol complex eluates, quercetin, - in aglycone or glycosidic form - was the main phytochemical identified to be covalently bound to peanut proteins. Peanut protein-bound cranberry and blueberry polyphenols significantly decreased IgE binding to peanut proteins at p<0.05 (38% and 31% decrease, respectively). Sensitized RBL-2H3 cells challenged with antigen and ionomycin in the presence of protein-cranberry and blueberry polyphenol complexes showed a significant (p<0.05) reduction in histamine and beta -hexosaminidase release (histamine: 65.5% and 65.8% decrease; beta -hexosaminidase: 60.7% and 45.4% decrease, respectively). The modification of peanut proteins with cranberry or blueberry polyphenols led to the formation of peanut protein-polyphenol complexes with significantly reduced allergenic potential. Future trials are warranted to investigate the immunomodulatory mechanisms of these protein-polyphenol complexes and the role of quercetin in their hypoallergenic potential.

Plant-derived foods rich in polyphenols are associated with several cardiometabolic health benefits, such as reduced postprandial hyperglycaemia. However, their impact on whole-body insulin sensitivity using the hyperinsulinaemic-euglycaemic clamp technique remains under-studied. We aimed to determine the effects of strawberry and cranberry polyphenols (SCP) on insulin sensitivity, glucose tolerance, insulin secretion, lipid profile, inflammation and oxidative stress markers in free-living insulin-resistant overweight or obese human subjects (n 41) in a parallel, double-blind, controlled and randomised clinical trial. The experimental group consumed an SCP beverage (333 mg SCP) daily for 6 weeks, whereas the Control group received a flavour-matched Control beverage that contained 0 mg SCP. At the beginning and at the end of the experimental period, insulin sensitivity was assessed by a hyperinsulinaemic-euglycaemic clamp, and glucose tolerance and insulin secretion by a 2-h oral glucose tolerance test (OGTT). Insulin sensitivity increased in the SCP group as compared with the Control group (+0·9 (sem 0·5)×10-3 v. -0·5 (sem 0·5)×10-3 mg/kg per min per pmol, respectively, P=0·03). Compared with the Control group, the SCP group had a lower first-phase insulin secretion response as measured by C-peptide levels during the first 30 min of the OGTT (P=0·002). No differences were detected between the two groups for lipids and markers of inflammation and oxidative stress. A 6-week dietary intervention with 333 mg of polyphenols from strawberries and cranberries improved insulin sensitivity in overweight and obese non-diabetic, insulin-resistant human subjects but was not effective in improving other cardiometabolic risk factors.

Plasma metabolome in young women following cranberry juice consumption were investigated using a global UHPLC-Q-Orbitrap-HRMS approach. Seventeen female college students, between 21 and 29 years old, were given either cranberry juice or apple juice for three days using a cross-over design. Plasma samples were collected before and after juice consumption. Plasma metabolomes were analyzed using UHPLC-Q-Orbitrap-HRMS followed by orthogonal partial least squares-discriminant analyses (OPLS-DA). S-plot was used to identify discriminant metabolites. Validated OPLS-DA analyses showed that the plasma metabolome in young women, including both exogenous and endogenous metabolites, were altered following cranberry juice consumption. Cranberry juice caused increases of exogenous metabolites including quinic acid, vanilloloside, catechol sulfate, 3,4-dihydroxyphenyl ethanol sulfate, coumaric acid sulfate, ferulic acid sulfate, 5-(trihydroxphenyl)-gamma-valerolactone, 3-(hydroxyphenyl)proponic acid, hydroxyphenylacetic acid and trihydroxybenzoic acid. In addition, the plasma levels of endogenous metabolites including citramalic acid, aconitic acid, hydroxyoctadecanoic acid, hippuric acid, 2-hydroxyhippuric acid, vanilloylglycine, 4-acetamido-2-aminobutanoic acid, dihydroxyquinoline, and glycerol 3-phosphate were increased in women following cranberry juice consumption. The metabolic differences and discriminant metabolites observed in this study may serve as biomarkers of cranberry juice consumption and explain its health promoting properties in human.