Publications des agents du Cirad

Cirad

Resveratrol formulated with a natural deep eutectic solvent inhibits active matrix metalloprotease-9 in hormetic conditions

Shamseddin A., Crauste C., Durand E., Villeneuve P., Dubois G., Durand T., Vercauteren J., Veas F.. 2017. European Journal of Lipid Science and Technology, 119 (11) : 9 p..

DOI: 10.1002/ejlt.201700171

Despite the promising anti-oxidant and anti-inflammatory effects of resveratrol (RES) on human health, pre-clinical and clinical studies are frequently disappointing, probably due to its low water-solubility and poor bioavailability. Even though a hormetic mode of action was clearly established for RES, the high doses commonly used to mitigate these issues, lead to adverse effects. Common hallmarks of multiple pathologies results from pathological-enhanced endothelial permeability due to both enhanced inflammation and matrix metalloprotease-9 (aMMP-9) activities. The main aim of this work was to optimize the RES capacity to inhibit aMMP-9 by using a new class of solvents, natural deep eutectic solvents (NADES) for a new RES formulation as compared with dimethyl-sulfoxide (DMSO). To obtain the appropriate NADES, 18 compounds combinations were prepared to select those exhibiting the optimized capacity to dissolve RES. The RES-NADES 1,2-propanediol:choline-chloride:water (PCW, 1:1:1 molar ratio) and compared with RES-DMSO for their aMMP-9-inhibitory capacities. Low concentrations of RES-NADES/PCW formulation exhibited both a biocompatible solubility and a strong increased aMMP-9-inhibitory activity, at least 10-fold, higher than RES-DMSO, reaching its hormetic mode of action. Following in vivo validations, some particular NADES could potentially be considered as the new generation of formulation for druggable compounds. Practical applications: Formulation of resveratrol in Natural Deep Eutectic solvents (NADES) optimizes its capacity to inhibit active matrix metalloprotease-9. The Resveratrol-NADES 1,2-propanediol:choline-was the most efficient and low concentrations exhibited both a biocompatible solubility and an increased aMMP-9-inhibitory activity, at least 10-fold, higher than RES-DMSO. Consequently, the NADES/PCW formulation allowed resveratrol to reach its hormetic mode of action. Following in vivo validations, some particular NADES could potentially be consider

Mots-clés : resvératrol; solvant

Documents associés

Article (a-revue à facteur d'impact)

Agents Cirad, auteurs de cette publication :