title: Paradoxical effects of polyphenolic compounds from Clusiaceae on angiogenesis.
abstract: Clusiaceae plants display high contents of xanthones and coumarins, the effects of which on endothelium, more particularly on angiogenesis, have not been assessed yet. We screened the capacity of six molecules from Clusiaceae--belonging to xanthones, coumarins and acid chromanes classes--to induce endothelium-dependent relaxation on mice aortic rings. Endothelial nitric oxide (NO) production was assessed in endothelial cell line using electron paramagnetic resonance technique. Then, the capacity of these molecules to induce capillary-like structures of endothelial cells was assessed. Cellular processes implicated in angiogenesis (adhesion, migration and proliferation) and Western blot analyses were then investigated. Among the tested molecules, isocalolongic acid (IA) and 2-deprenylrheediaxanthone (DRX) induced an endothelium-dependent relaxation of the aorta associated with an increase of NO production in endothelial cells. Using in vitro and ex vivo angiogenesis assays, it was shown that IA treatment promoted the formation of capillary-like network. In contrast, DRX prevented the ability of vascular endothelial growth factor (VEGF) to increase the formation of capillary-like network. IA increased endothelial cell proliferation while DRX decreased all cellular processes of angiogenesis. Western blot analysis showed that IA increased VEGF expression whereas DRX decreased ICAM-1 expression. Altogether, these data allowed identifying isolated molecules from Clusiaceae that exhibit a potential activity towards the modulation of endothelium-dependent relaxation involving NO release. Interestingly, they also highlighted paradoxical effects of the two compounds on cellular angiogenic processes, IA being pro-angiogenic and DRX anti-angiogenic.
authors.affiliation: INSERM UMR U1063, IBS-IRIS, Université d'Angers, Rue des Capucins, F-49100 Angers Cedex, France. alexis.lavaud@gmail.com
authors.forename: Alexis
authors.initials: A
authors.lastname: Lavaud
authors.forename: Raffaella
authors.initials: R
authors.lastname: Soleti
authors.forename: Anne-Emmanuelle
authors.initials: AE
authors.lastname: Hay
authors.forename: Pascal
authors.initials: P
authors.lastname: Richomme
authors.forename: David
authors.initials: D
authors.lastname: Guilet
authors.forename: Ramaroson
authors.initials: R
authors.lastname: Andriantsitohaina
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D001011:Aorta / Q000187:drug effects; D015153:Blotting, Western; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D028084:Clusiaceae / Q000737:chemistry*; D004730:Endothelium, Vascular / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D015394:Molecular Structure; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D009569:Nitric Oxide / Q000378:metabolism; D059808:Polyphenols / Q000737:chemistry* / Q000494:pharmacology*; D046509:Tissue Culture Techniques
chemical_list: D059808:Polyphenols; D009569:Nitric Oxide; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid