Inhibitory effects of blueberry root methanolic extract on degranulation in KU812F cells
ABSTRACT The effect of blueberry (Vaccinium angustifolium) root methanolic extract (BRM) on the A23187 plus phorbol myristate acetate (PMA)-induced degranulation in human basophilic
KU812F cells was investigated. The total phenolic content (TPC) was 170±1.9 mg gallic acid equivalents (GAE)/g BRM. BRM reduced
levels of histamine and β-hexosaminidase released from stimulated KU812F cells. Intracellular calcium concentration ([Ca2+]i) were determined by spectrofluorometric analysis using Fura 2-AM was found to be reduced by BRM with dose-dependent manner.
Moreover, Western blot analysis revealed that protein kinase C (PKC) translocation was inhibited by BRM with dose-dependent
manner. These results indicated that BRM inhibited histamine and β-hexosaminidase through the suppression of Ca2+ influx and PKC translocation. Therefore, we suggest that BRM is potent inhibitor of degranulation in mast cells and basophils,
and may be useful in preventing the allergic reactions.
-degranulation-calcium influx-protein kinase C
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ABSTRACT: Regulation of the matrix metalloproteinases (MMPs), the major mediators of extracellular matrix (ECM) degradation, is crucial to regulate ECM proteolysis, which is important in metastasis. This study examined the effects of 3 flavonoid-enriched fractions (a crude fraction, an anthocyanin-enriched fraction, and a proanthocyanidin-enriched fraction), which were prepared from lowbush blueberries (Vaccinium angustifolium), on MMP activity in DU145 human prostate cancer cells in vitro. Using gelatin gel electrophoresis, MMP activity was evaluated from cells after 24-hr exposure to blueberry fractions. All fractions elicited an ability to decrease the activity of MMP-2 and MMP-9. Of the fractions tested, the proanthocyanidin-enriched fraction was found to be the most effective at inhibiting MMP activity in these cells. No induction of either necrotic or apoptotic cell death was noted in these cells in response to treatment with the blueberry fractions. These findings indicate that flavonoids from blueberry possess the ability to effectively decrease MMP activity, which may decrease overall ECM degradation. This ability may be important in controlling tumor metastasis formation.Biochemistry and Cell Biology 11/2005; 83(5):637-43. DOI:10.1139/o05-063 · 2.35 Impact Factor
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ABSTRACT: Polymethoxy flavones (PMFs) are present in fruit tissues of Citrus species. It has been reported that flavonoids isolated from several Citrus have been shown to suppress the degranulation as inferred by histamine release in rat basophilic leukemia RBL-2H3 cells. In this study, we examined the effect of PMFs (PMF-1: 6,7,4',5'-tetramethoxy-5-monohydroxyflavone, PMF-2: 5,6,8,3',6'-pentamethoxy flavone, PMF-3: 5,6,7,3',4',5'-hexamethoxy flavone) on the degranulation in RBL-2H3 cells. All the PMFs suppressed the degranulation from Ag-stimulated RBL-2H3 cells. Interestingly, PMF-combination (PMF-1+PMF-2; PMF-1+PMF-3) treatment enhanced the inhibition of degranulation compared with PMF-single treatment. In order to clarify the inhibitory mechanism of degranulation by PMFs, we examined the activation of intracellular signaling molecules such as Lyn, Syk, and PLCgammas. All the PMFs significantly suppressed the activation of Syk and PLCgammas. In Ag-mediated activation of Fc epsilonRI on mast cells, three major subfamilies of mitogen-activated protein kinases, especially ERK44/42, were activated. These PMFs reduced the level of phospho-ERKs. The intracellular free Ca(2+) concentration ([Ca(2+)]i) was elevated by Fc epsilonRI activation, and PMF treatment reduced the elevation of [Ca(2+)]i by suppressing Ca(2+) influx. Thus, it was suggested that the suppression of Ag-stimulated degranulation by these PMFs mainly is due to the Syk/PLCgammas/PKC pathway and Ca(2+) influx. Furthermore, to be noted in the PMF-combination treatment, inactivation of Syk was enhanced compared with PMF-single treatment. But the inhibitory effect of degranulation by PMF-combination treatment was not associated with the suppression of Ca(2+) influx.Bioorganic & medicinal chemistry 08/2008; 16(16):7592-8. DOI:10.1016/j.bmc.2008.07.018 · 2.82 Impact Factor
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ABSTRACT: Brain aging is characterized by the continual concession to battle against insults accumulated over the years. One of the major insults is oxidative stress, which is the inability to balance and to defend against the cellular generation of reactive oxygen species (ROS). These ROS cause oxidative damage to nucleic acid, carbohydrate, protein, and lipids. Oxidative damage is particularly detrimental to the brain, where the neuronal cells are largely post-mitotic. Therefore, damaged neurons cannot be replaced readily via mitosis. During normal aging, the brain undergoes morphological and functional modifications resulting in the observed behavioral declines such as decrements in motor and cognitive performance. These declines are augmented by neurodegenerative diseases including amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), and Parkinson's disease (PD). Research from our laboratory has shown that nutritional antioxidants, such as the polyphenols found in blueberries, can reverse age-related declines in neuronal signal transduction as well as cognitive and motor deficits. Furthermore, we have shown that short-term blueberry (BB) supplementation increases hippocampal plasticity. These findings are briefly reviewed in this paper.Neurobiology of Aging 01/2006; 26 Suppl 1:128-32. DOI:10.1016/j.neurobiolaging.2005.08.007 · 4.85 Impact Factor