title: Flavanone metabolites decrease monocyte adhesion to TNF-α-activated endothelial cells by modulating expression of atherosclerosis-related genes.
abstract: Flavanones are found specifically and abundantly in citrus fruits. Their beneficial effect on vascular function is well documented. However, little is known about their cellular and molecular mechanisms of action in vascular cells. The goal of the present study was to identify the impact of flavanone metabolites on endothelial cells and decipher the underlying molecular mechanisms of action. We investigated the impact of naringenin and hesperetin metabolites at 0·5, 2 and 10 μM on monocyte adhesion to TNF-α-activated human umbilical vein endothelial cells (HUVEC) and on gene expression. Except hesperetin-7-glucuronide and naringenin-7-glucuronide (N7G), when present at 2 μM, flavanone metabolites (hesperetin-3'-sulphate, hesperetin-3'-glucuronide and naringenin-4'-glucuronide (N4'G)) significantly attenuated monocyte adhesion to TNF-α-activated HUVEC. Exposure of both monocytes and HUVEC to N4'G and N7G at 2 μM resulted in a higher inhibitory effect on monocyte adhesion. Gene expression analysis, using TaqMan Low-Density Array, revealed that flavanone metabolites modulated the expression of genes involved in atherogenesis, such as those involved in inflammation, cell adhesion and cytoskeletal organisation. In conclusion, physiologically relevant concentrations of flavanone metabolites reduce monocyte adhesion to TNF-α-stimulated endothelial cells by affecting the expression of related genes. This provides a potential explanation for the vasculoprotective effects of flavanones.
authors: INRA, UMR 1019, UNH, CRNH Auvergne, F-63000 Clermont-Ferrand, France.
authors: Audrey
authors: A
authors: Chanet
authors: Dragan
authors: D
authors: Milenkovic
authors: Sylvain
authors: S
authors: Claude
authors: Jeanette A M
authors: JA
authors: Maier
authors: Muhammad
authors: M
authors: Kamran Khan
authors: Njara
authors: N
authors: Rakotomanomana
authors: Svitlana
authors: S
authors: Shinkaruk
authors: Annie M
authors: AM
authors: Bérard
authors: Catherine
authors: C
authors: Bennetau-Pelissero
authors: Andrzej
authors: A
authors: Mazur
authors: Christine
authors: C
authors: Morand
mesh_terms: D050197:Atherosclerosis / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects*; D042783:Endothelial Cells / Q000187:drug effects*; D044950:Flavanones / Q000378:metabolism* / Q000494:pharmacology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D020719:Glucuronides / Q000494:pharmacology; D006569:Hesperidin / Q000494:pharmacology; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007249:Inflammation; D009000:Monocytes / Q000166:cytology / Q000187:drug effects*; D013431:Sulfates / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D044950:Flavanones; D020719:Glucuronides; D013431:Sulfates; D014409:Tumor Necrosis Factor-alpha; D006569:Hesperidin; C005273:naringenin; C013015:hesperetin