« Previous AbstractDrought affects carbon partitioning into volatile organic compound biosynthesis in Scots pine needles    Next AbstractEvaluation of worker exposure to asphalt paving fumes using traditional and nontraditional techniques »

Free Radic Biol Med

Title:		Anthocyanins and their gut metabolites attenuate monocyte adhesion and transendothelial migration through nutrigenomic mechanisms regulating endothelial cell permeability
Author(s):		Krga I; Tamaian R; Mercier S; Boby C; Monfoulet LE; Glibetic M; Morand C; Milenkovic D;
Address:		"Universite Clermont Auvergne, INRA, UNH, CRNH Auvergne, F-63000 Clermont-Ferrand, France; Centre of Research Excellence in Nutrition and Metabolism, Institute for Medical Research, University of Belgrade, Belgrade, Serbia. Research and Development Department, National Institute for Research and Development for Cryogenic and Isotopic Technologies, RO-240050 Ramnicu Valcea, Romania; SC Biotech Corp SRL, RO-240050 Ramnicu Valcea, Romania. Electronic address: radu.tamaian@icsi.ro. Universite Clermont Auvergne, INRA, UNH, CRNH Auvergne, F-63000 Clermont-Ferrand, France. Universite Clermont Auvergne, INRA, VetAgro Sup, UMR Herbivores, Metabolism Exploration Platform, F-63122 Saint-Genes-Champanelle, France. Centre of Research Excellence in Nutrition and Metabolism, Institute for Medical Research, University of Belgrade, Belgrade, Serbia. Universite Clermont Auvergne, INRA, UNH, CRNH Auvergne, F-63000 Clermont-Ferrand, France; Department of Internal Medicine, Division of Cardiovascular Medicine, School of Medicine, University of California Davis, Davis, CA 95616, United States of America. Electronic address: dragan.milenkovic@inra.fr"
Journal Title:		Free Radic Biol Med
Year:		2018
Volume:		20180628
Issue:
Page Number:		364 - 379
DOI:		10.1016/j.freeradbiomed.2018.06.027
ISSN/ISBN:		1873-4596 (Electronic) 0891-5849 (Linking)
Abstract:		"Cardioprotective effects of dietary anthocyanins are partly attributed to their ability to maintain endothelial function. However, the underlying cellular and molecular mechanisms of action are not fully understood. This study aimed to evaluate the effect of anthocyanins and their gut metabolites, at physiologically-relevant conditions, on endothelial cell (EC) function and decipher the underlying molecular mechanisms of action using integrated omics approaches. Primary EC were treated with a mixture of 0.1?ª+muM cyanidin-3-arabinoside, 0.1?ª+muM cyanidin-3-galactoside, 0.1?ª+muM cyanidin-3-glucoside, 0.1?ª+muM delphinidin-3-glucoside, 0.1?ª+muM peonidin-3-glucoside and 0.5?ª+muM 4-hydroxybenzaldehyde for 3?ª+h or a mixture of gut metabolites: 0.2?ª+muM protocatechuic, 2?ª+muM vanillic, 1?ª+muM ferulic and 2?ª+muM hippuric acids for 18?ª+h. Also, successive exposure of EC to both mixtures was performed to mimic anthocyanin pharmacokinetics following their intake. Inflammatory stress was induced using TNFalpha and monocytes added to assess adhesion and transmigration. Effects of these mixtures on gene, miRNA expression and their potential interaction with cell signalling were investigated. Anthocyanins and their gut metabolites significantly reduced monocyte adhesion and transendothelial migration. Gene expression analysis, using macroarrays, showed that tested compounds modulated the expression of genes involved in cell-cell adhesion, cytoskeleton organisation or focal adhesion. Bioinformatics analyses of gene expression data identified potential transcription factors involved in the observed nutrigenomic effects and signalling proteins regulating their activity. Molecular docking revealed cell signalling proteins to which these bioactives may bind to and potentially affect their activity and the activation of downstream signalling, effects that were in agreement with the results of Western blot analyses. Microarray analysis showed that anthocyanins and their gut metabolites affected miRNA expression in EC, especially those involved in regulation of EC permeability, contributing to the observed changes in EC function. Integration of these results revealed endothelial-protective properties of anthocyanins and their gut metabolites and deciphered new underlying multi-target and multi-layered mode of action"
Keywords:		Anthocyanins/metabolism/*pharmacology Capillary Permeability/*drug effects Cell Adhesion/drug effects/genetics Human Umbilical Vein Endothelial Cells/*drug effects/metabolism Humans Monocytes/*drug effects Nutrigenomics Transendothelial and Transepithelia;
Notes:		"MedlineKrga, Irena Tamaian, Radu Mercier, Sylvie Boby, Celine Monfoulet, Laurent-Emanuel Glibetic, Marija Morand, Christine Milenkovic, Dragan eng 2018/07/03 Free Radic Biol Med. 2018 Aug 20; 124:364-379. doi: 10.1016/j.freeradbiomed.2018.06.027. Epub 2018 Jun 28"