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Cranberry product decreases fat accumulation in Caenorhabditis elegans.

Posted: 
August 22, 2016
Authors: 
Sun Q, Yue Y, Shen P, Yang JJ, Park Y.
Journal: 
Journal of Medicinal Food; 2016. 19(4):427-433.
Abstract: 

Cranberry phenolic compounds have been linked to many health benefits. A recent report suggested that cranberry bioactives inhibit adipogenesis in 3T3-L1 adipocytes. Thus, we investigated the effects and mechanisms of the cranberry product (CP) on lipid metabolism using the Caenorhabditis elegans (C. elegans) model. CP (0.016% and 0.08%) dose-dependently reduced overall fat accumulation in C. elegans (N2, wild type) by 43% and 74%, respectively, without affecting its pumping rates or locomotive activities. CP decreased fat accumulation in aak-2 (an ortholog of AMP-activated kinase alpha ) and tub-1 (an ortholog of TUBBY) mutants significantly, but only minimal effects were observed in sbp-1 (an ortholog of sterol response element-binding protein-1) and nhr-49 (an ortholog of peroxisome proliferator-activated receptor- alpha ) mutant strains. We further confirmed that CP downregulated sbp-1, cebp, and hosl-1 (an ortholog of hormone-sensitive lipase homolog) expression, while increasing the expression of nhr-49 in wild-type C. elegans. These results suggest that CP could effectively reduce fat accumulation in C. elegans dependent on sbp-1, cebp, and nhr-49, but not aak-2 and tub-1.

Critical reevaluation of the 4-(dimethylamino)cinnamaldehyde assay: cranberry proanthocyanidin standard is superior to procyanidin A2 dimer for accurate quantification of proanthocyanidins in cranberry products.

Posted: 
August 22, 2016
Authors: 
Krueger, C. G. Chesmore, N. Chen Xin Parker, J. Khoo, C. Marais, J. P. J. Shanmuganayagam, D. Crump, P. Reed, J. D.
Journal: 
Journal of Functional Foods; 2016. 22:13-19.
Abstract: 

The 4-(dimethylamino)cinnamaldehyde (DMAC) assay is currently used to quantify proanthocyanidin (PAC) content in cranberry products. In a multi-operator/multi-day study design, a cranberry proanthocyanidin (c-PAC) standard was compared to procyanidin A2 (ProA2) dimer for accurate quantification of PAC in commercial cranberry juices, lab generated cranberry blends and cranberry powders. The c-PAC standard reflects the structural heterogeneity of cranberry PAC degree of polymerization, hydroxylation pattern and ratios of 'A-type' to 'B-type' interflavanyl bonds. Use of the c-PAC standard to quantify PAC content in cranberry samples resulted in values that were 3.6 times higher than those determined by ProA2. Overall, there was no effect (P>0.05) of operator or day on estimation of PAC concentration. The adoption of c-PAC standard should be considered as an improvement over the use of ProA2 for accurate quantification of cranberry PAC. Improved standardization of bioactive PAC components in functional cranberry foods will aid in establishment of dosage guidelines.

Effect of cranberry (Vaccinium macrocarpon) oligosaccharides on the formation of advanced glycation end-products.

Posted: 
August 22, 2016
Authors: 
Sun J, Liu W, Ma H, Marais JPJ, Khoo C, Dain JA, Rowley DC, Seeram NP
Journal: 
Journal of Berry Research; 2016. 6(2):149-158
Abstract: 

BACKGROUND: The formation and accumulation of advanced glycation end-products (AGEs) are implicated in several chronic human illnesses including type-2 diabetes, renal failure, and neurodegenerative diseases. The cranberry (Vaccinium macrocarpon) fruit has been previously reported to show anti-AGEs effects, attributed primarily to its phenolic constituents. However, there is lack of similar data on the non-phenolic constituents found in the cranberry fruit, in particular, its carbohydrate constituents. Herein, a chemically characterized oligosaccharide-enriched fraction purified from the cranberry fruit was evaluated for its potential anti-AGEs and free radical scavenging effects. OBJECTIVE: The aim of this study was to evaluate the in vitro anti-AGEs and free radical scavenging effects of a chemically characterized oligosaccharide-enriched fraction purified from the North American cranberry (Vaccinium macrocarpon) fruit. METHOD: The cranberry oligosaccharide-enriched fraction was purified from cranberry hull powder and characterized based on spectroscopic and spectrometric (NMR, MALDI-TOF-MS, and HPAEC-PAD) data. The oligosaccharide-enriched fraction was evaluated for its anti-AGEs and free radical scavenging effects by the bovine serum albumin-fructose, and DPPH assays, respectively. RESULTS: Fractionation of cranberry hull material yielded an oligosaccharide-enriched fraction named Cranf1b-CL. The 1H NMR and MALDI-TOF-MS revealed that Cranf1b-CL consists of oligosaccharides ranging primarily from 6-mers to 9-mers. The monosaccharide composition of Cranf1b-CL was arabinose (25%), galactose (5%), glucose (47%) and xylose (23%). In the bovine serum albumin-fructose assay, Cranf1b-CL inhibited AGEs formation in a concentration-dependent manner with comparable activity to the synthetic antiglycating agent, aminoguanidine, used as the positive control (57 vs. 75%; both at 500 micro g/mL). In the DPPH free radical scavenging assay, Cranf1b-CL showed superior activity to the synthetic commercial antioxidant, butylated hydroxytoluene, used as the positive control (IC50=680 vs. 2200 micro g/mL, respectively). CONCLUSION: The in vitro anti-AGEs and free radical scavenging effects of cranberry oligosaccharides support previous data suggesting that these constituents may also contribute to biological effects of the whole fruit beyond its phenolic constituents alone. Also, this is the first study to evaluate a chemically characterized oligosaccharide fraction purified from the North American cranberry fruit for anti-AGEs and free radical scavenging properties.

Effect of glycated albumin and cranberry components on interleukin-6 and matrix metalloproteinase-3 production by human gingival fibroblasts

Posted: 
August 22, 2016
Authors: 
Tipton DA; Hatten AA; Babu JP; Dabbous MKh.
Journal: 
Journal of Periodontal Research. 51(2):228-36
Abstract: 

BACKGROUND AND OBJECTIVE: Gingival fibroblasts have the potential to participate in periodontal inflammation and breakdown, producing interleukin (IL)-6 and matrix metalloproteinase (MMP)-3. Advanced glycation end products (AGEs), formed during diabetic hyperglycemia, might aggravate periodontal inflammation. The cranberry contains anti-inflammatory polyphenols, which inhibit proinflammatory activities of lipopolysaccharide (LPS)- and IL-1beta-stimulated human cells. Little is known of its effects on gingival fibroblast IL-6 or MMP-3 production stimulated by AGEs. The objectives were to determine cranberry effects on IL-6 and MMP-3 production by gingival fibroblasts exposed to the representative AGE, glycated human serum albumin (G-HSA), or LPS +/- G-HSA. MATERIAL AND METHODS: Cranberry high molecular weight non-dialyzable material (NDM), was derived from cranberry juice. Normal human gingival fibroblasts were incubated with G-HSA or normal HSA or Porphyromonas gingivalis LPS (1 mug/mL) +/- G-HSA, in the presence or absence of preincubation with NDM. IL-6 and MMP-3 were measured by enzyme-linked immunosorbent assay. Data were analyzed using one-way analysis of variance and Scheffe's F procedure. RESULTS: IL-6 production was stimulated by G-HSA or LPS (p

Effects of cranberry components on IL-1beta-stimulated production of IL-6, IL-8 and VEGF by human TMJ synovial fibroblasts.

Posted: 
August 22, 2016
Authors: 
Tipton DA; Christian J; Blumer A.
Journal: 
Archives of Oral Biology. 68:88-96, 2016 Aug
Abstract: 

OBJECTIVE: Osteoarthritis (OA) in the TMJ is characterized by deterioration of articular cartilage and secondary inflammatory changes. Interleukin-1beta (IL-1beta) stimulates IL-6, IL-8, and vascular endothelial growth factor (VEGF) in synovial fluid of TMJ with internal derangement and bony changes. The cranberry (Vaccinium macrocarpon) contains polyphenolic compounds that inhibit production of pro-inflammatory molecules by gingival cells in response to several stimulators. This study examined effects of cranberry components on IL-1beta-stimulated IL-6, IL-8, and VEGF production by human TMJ synovial fibroblast-like cells. DESIGN: Cranberry high molecular weight non-dialyzable material (NDM) was derived from cranberry juice. Human TMJ synovial fibroblast-like cells from joints with degenerative OA and an ankylosed TMJ without degeneration were incubated with IL-1beta (0.001-1nM)+/-NDM (25-250mug/ml) (2h preincubation). Viability was assessed via activity of a mitochondrial enzyme. IL-6, IL-8, and VEGF in culture supernatants were measured by ELISA; NF-kappaB and AP-1 transcription factors were measured in nuclear extracts via binding to specific oligonucleotides. DATA ANALYSIS: ANOVA and Scheffe's F procedure for post hoc comparisons. RESULTS: NDM did not affect cell viability but inhibited IL-1beta stimulated IL-6, IL-8, and VEGF production in all cell lines (p

Identification and quantification of novel cranberry-derived plasma and urinary (poly)phenols.

Posted: 
August 22, 2016
Authors: 
Feliciano R.P., Boeres A., Massacessi L., Istas G., Ventura M.R., Nunes Dos Santos C., Heiss C., Rodriguez-Mateos A.
Journal: 
Archives of Biochemistry and Biophysics. 599 (pp 31-41), 2016
Abstract: 

Cranberries are a rich source of (poly)phenols, in particular proanthocyanidins, anthocyanins, flavonols, and phenolic acids. However, little is known about their bioavailability in humans. We investigated the absorption, metabolism, and excretion of cranberry (poly)phenols in plasma and urine of healthy young men after consumption of a cranberry juice (787 mg (poly)phenols). A total of 60 cranberry-derived phenolic metabolites were identified using UPLC-Q-TOF-MS analysis with authentic standards. These included sulfates of pyrogallol, valerolactone, benzoic acids, phenylacetic acids, glucuronides of flavonols, as well as sulfates and glucuronides of cinnamic acids. The most abundant plasma metabolites were small phenolic compounds, in particular hippuric acid, catechol-O-sulfate, 2,3-dihydroxybenzoic acid, phenylacetic acid, isoferulic acid, 4-methylcatechol-O-sulfate, alpha-hydroxyhippuric acid, ferulic acid 4-O-sulfate, benzoic acid, 4-hydroxyphenyl acetic acid, dihydrocaffeic acid 3-O-sulfate, and vanillic acid-4-O-sulfate. Some benzoic acids, cinnamic acids, and flavonol metabolites appeared in plasma early, at 1-2 h post-consumption. Others such as phenylacetic acids, benzaldehydes, pyrogallols, catechols, hippuric and dihydrocinnamic acid derivatives appear in plasma later (Tmax 4-22 h). The 24 h urinary recovery with respect to the amount of (poly)phenols consumed was 6.2%. Our extensive description of the bioavailability of cranberry (poly)phenols lays important groundwork necessary to start understanding the fate of these compounds in humans.

Inhibition of herpes simplex type 1 and type 2 infections by Oximacro, a cranberry extract with a high content of A-type proanthocyanidins (PACs-A)

Posted: 
August 22, 2016
Authors: 
Terlizzi ME; Occhipinti A; Luganini A; Maffei ME; Gribaudo G.
Journal: 
Antiviral Research. 132 (pp 154-164),
Abstract: 

In the absence of efficient preventive vaccines, topical microbicides offer an attractive alternative in the prevention of Herpes simplex type 1 (HSV-1) and type 2 (HSV-2) infections. Because of their recognized anti-adhesive activity against bacterial pathogens, cranberry (Vaccinium macrocarpon Ait.) extracts may represent a natural source of new antiviral microbicides. However, few studies have addressed the applications of cranberry extract as a direct-acting antiviral agent. Here, we report on the ability of the novel cranberry extract Oximacro and its purified A-type proanthocyanidins (PACs-A), to inhibit HSV-1 and HSV-2 replication in vitro. Analysis of the mode of action revealed that Oximacro prevents adsorption of HSV-1 and HSV-2 to target cells. Further mechanistic studies confirmed that Oximacro and its PACs-A target the viral envelope glycoproteins gD and gB, thus resulting in the loss of infectivity of HSV particles. Moreover, Oximacro completely retained its anti-HSV activity even at acidic pHs (3.0 and 4.0) and in the presence of 10% human serum proteins; conditions that mimic the physiological properties of the vagina - a potential therapeutic location for Oximacro. Taken together, these findings indicate Oximacro as an attractive candidate for the development of novel microbicides of natural origin for the prevention of HSV infections.

Liquid chromatography with tandem mass spectrometry quantification of urinary proanthocyanin A2 dimer and its potential use as a biomarker of cranberry intake

Posted: 
August 22, 2016
Authors: 
Walsh J.M., Ren X., Zampariello C., Polasky D.A., McKay D.L., Blumberg J.B., Chen C.-Y.O.
Journal: 
Journal of Separation Science. 39 (2) (pp 342-349), 2016.
Abstract: 

The lack of a biomarker for the consumption of cranberries has confounded the interpretation of several studies investigating the effect of cranberry products, especially juices, on health outcomes. The objectives of this pilot study were to develop a liquid chromatography tandem mass spectrometric method for the quantification of the proanthocyanin dimer A-2 in human urine and validate urinary proanthocyanin dimer A-2 as a biomarker of cranberry intake. Five healthy, nonsmoking, premenopausal women (20-30 years of age, body mass index: 18.5-25 kg/m2) were assigned to consume a cranberry beverage containing 140 mg proanthocyanin and 35 kilocalories at 237 mL/day, according to a weekly dosing schedule for 7 weeks. Eleven 24 h and morning spot urine samples each were collected from each subject. A reliable, sensitive method for the detection of proanthocyanin dimer A-2 in urine using liquid chromatography with tandem mass spectrometry was developed with a limit of quantitation of 0.25 ng/mL and a relative standard deviation of 7.26%, precision of 5.7%, and accuracy of 91.7%. While proanthocyanin dimer A-2 was quantifiable in urine, it did not appear to be excreted in a concentration that corresponded to the dosing schedule and intake of cranberry juice.

NMR-based metabolomics reveals urinary metabolome modifications in female Sprague-Dawley rats by cranberry procyanidins.

Posted: 
August 22, 2016
Authors: 
Liu H., Tayyari F., Edison A.S., Su Z., Gu L.
Journal: 
Journal of Nutritional Biochemistry. 34 (pp 136-145), 2016
Abstract: 

A 1H NMR global metabolomics approach was used to investigate the urinary metabolome changes in female rats gavaged with partially purified cranberry procyanidins (PPCP) or partially purified apple procyanidins (PPAP). After collecting 24-h baseline urine, 24 female Sprague-Dawley rats were randomly separated into two groups and gavaged with PPCP or PPAP twice using a dose of 250 mg extracts per kilogram body weight. The 24-h urine samples were collected after the gavage. Urine samples were analyzed using 1H NMR. Multivariate analyses showed that the urinary metabolome in rats was modified after administering PPCP or PPAP compared to baseline urine metabolic profiles. 2D 1H-13C HSQC NMR was conducted to assist identification of discriminant metabolites. An increase of hippurate, lactate and succinate and a decrease of citrate and alpha-ketoglutarate were observed in rat urine after administering PPCP. Urinary levels of d-glucose, d-maltose, 3-(3'-hydroxyphenyl)-3-hydroxypropanoic acid, p-hydroxyphenylacetic acid, formate and phenol increased but citrate, alpha-ketoglutarate and creatinine decreased in rats after administering PPAP. Furthermore, the NMR analysis showed that the metabolome in the urine of rats administered with PPCP differed from those gavaged with PPAP. Compared to PPAP, PPCP caused an increase of urinary excretion of hippurate but a decrease of 3-(3'-hydroxyphenyl)-3-hydroxypropanoic acid, p-hydroxyphenylacetic acid and phenol. These metabolome changes caused by cranberry procyanidins may help to explain its reported health benefits and identify biomarkers of cranberry procyanidin intake.

Review of dried fruits: phytochemicals, antioxidant efficacies, and health benefits.

Posted: 
August 22, 2016
Authors: 
Chang SK, Alasalvar C, Shahidi F
Journal: 
Journal of Functional Foods; 2016. 21:113-132.
Abstract: 

Dried fruits, which serve as important healthful snacks worldwide, provide a concentrated form of fresh fruits. They are nutritionally equivalent to fresh fruits in smaller serving sizes, ranging from 30 to 43 g depending on the fruit, in current dietary recommendation in different countries. Daily consumption of dried fruits is recommended in order to gain full benefit of essential nutrients, health-promoting phytochemicals, and antioxidants that they contain, together with their desirable taste and aroma. Recently, much interest in the health benefits of dried fruits has led to many in vitro and in vivo (animal and human intervention) studies as well as the identification and quantification of various groups of phytochemicals. This review discusses phytochemical compositions, antioxidant efficacies, and potential health benefits of eight traditional dried fruits such as apples, apricots, dates, figs, peaches, pears, prunes, and raisins, together with dried cranberries. Novel product formulations and future perspectives of dried fruits are also discussed. Research findings from the existing literature published within the last 10 years have been compiled and summarised.

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