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

Shamseddin Aly, Crauste Céline, Durand Erwann, Villeneuve Pierre, Dubois Gregor, Pavlickova Teresa, Durand Thierry, Vercauteren Joseph, Veas Francisco. 2018. Resveratrol-Linoleate protects from exacerbated endothelial permeability via a drastic inhibition of the MMP-9 activity. Bioscience Reports, 38 (4):BSR20171712, 13 p.

Quartile : Q3, Sujet : BIOCHEMISTRY & MOLECULAR BIOLOGY / Quartile : Q3, Sujet : CELL BIOLOGY

Résumé : 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 µM), when dissolved in a natural deep eutectic solvent (NADES), composed of an equimolar content of 1,2-propanediol:choline chloride (ChCl):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-α-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.

Classification Agris : L50 - Physiologie et biochimie animales
L73 - Maladies des animaux

Champ stratégique Cirad : Axe 4 (2014-2018) - Santé des animaux et des plantes

Auteurs et affiliations

• Shamseddin Aly, IRD (FRA)
• Crauste Céline, IBMM (FRA)
• Durand Erwann, CIRAD-PERSYST-UMR IATE (FRA) ORCID: 0000-0002-0306-8081
• Villeneuve Pierre, CIRAD-PERSYST-UMR IATE (FRA) ORCID: 0000-0003-1685-1494
• Dubois Gregor, IRD (FRA)
• Pavlickova Teresa, IBMM (FRA)
• Durand Thierry, IBMM (FRA)
• Vercauteren Joseph, IBMM (FRA) - auteur correspondant
• Veas Francisco, IRD (FRA) - auteur correspondant

Source : Cirad-Agritrop (https://agritrop.cirad.fr/588538/)

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