Resveratrol-Linoleate protects from exacerbated endothelial permeability via a drastic inhibition of the MMP-9 activity

Autor: Shamseddin, A., Crauste, C., Durand, E., Villeneuve, P., Dubois, G., Pavlickova, T., Durand, T., Vercauteren, J., Veas, Francisco
Přispěvatelé: LIPMC, Institut de Recherche pour le Développement (IRD), Faculty of Biotechnology, Misr University for Science & Technology (MUST), Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Ingénierie des Agro-polymères et Technologies Émergentes (UMR IATE), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université de Montpellier (UM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), IF-EBOLA action from the EC-H2020 [grant number 666102], French Research Institute for Development (IRD), French National Center for Scientific Research (CNRS)., Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Institut National de la Recherche Agronomique (INRA)
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Zdroj: Bioscience Reports
Bioscience Reports, Portland Press, 2018, 38 (4), pp.BSR20171712. ⟨10.1042/BSR20171712⟩
Bioscience Reports, 2018, 38 (4), pp.BSR20171712. ⟨10.1042/BSR20171712⟩
Bioscience Reports 4 (38), BSR20171712. (2018)
ISSN: 0144-8463
1573-4935
DOI: 10.1042/BSR20171712⟩
Popis: Gelatinolytic matrix metalloproteinases (MMP-2, -9) play a critical role not only in mammals physiology but also during inflammation and healing processes. The natural stilbenoid, resveratrol (RES), exhibits potent antioxidant effects, in a hormetic mode of action, and is known to inhibit MMP-9. However, RES administration exhibits major issues, including poor bioavailability and water solubility, hampering its potential therapeutic effect in vivo. In the present study, we synthesized and evaluated five novel RES-lipid conjugates to increase their cell membrane penetration and improve their bioavailability. The best in vitro MMP-9 inhibitory activity of RES-lipids conjugates was observed with RES-linoleic acid (LA) (5 mu M), when dissolved in a natural deep eutectic solvent (NADES), composed of an equimolar content of 1,2-propanediol:choline chloride (ChCI):water. The inhibition of MMP-9 expression by RES-LA in activated THP-1 monocytes, was, at least due to the deactivation of ERK1/2 and JNK1/2 MAP kinase signaling pathways. Moreover, RES-LA exhibited a strong effect protecting the TNF-alpha-induced exacerbated permeability in an HUVEC in vitro monolayer (by 81%) via the integrity protection of intercellular junction proteins from the MMP-9 activity. This effect was confirmed by using several complementary approaches including, the real-time monitoring of trans-endothelial electric resistance (TEER), the Transwell HUVEC permeability level, the microscopic examination of the platelet endothelial cell adhesion molecule-1 (CD31/PECAM-1) integrity as well as the fluorescence in intercellular spaces. Consequently, following this strong in vitro proof-of-concept, there is a need to test this promising RES-lipid derivative compound to control the pathological endothelial permeability in vivo.
Databáze: OpenAIRE
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