Implementation of an Enzyme Membrane Reactor to Intensify the α-O-Glycosylation of Resveratrol Using Cyclodextrins

Abstract

The O-glycosylation of resveratrol increases both its solubility in water and its bioavailability while preventing its oxidation, allowing a more efficient use of this molecule as a bioactive ingredient in pharmaceutical and cosmetic applications. Resveratrol O-glycosides can be obtained by enzymatic reactions. Recent developments have made it possible to selectively obtain resveratrol α-glycosides from the β-cyclodextrin–resveratrol complex in water with a yield of 35%. However, this yield is limited by the partial hydrolysis of the resveratrol glycosides produced during the reaction. In this study, we propose to intensify this enzymatic reaction by coupling the enzymatic reactor to a membrane process. Firstly, membrane screening was carried out at the laboratory scale and led to the choice of a GE polymeric membrane with a cut-off of 1 kDa. This membrane allowed the retention of 65% of the β-cyclodextrin–resveratrol complex in the reaction medium and the transfer of 70% of the resveratrol α-O-glycosides in the permeate. In a second step, this membrane was used in an enzymatic membrane reactor and improved the yield of the enzymatic glycosylation up to 50%.

A Comparative Study of Rutin and Rutin Glycoside: Antioxidant Activity, Anti-Inflammatory Effect, Effect on Platelet Aggregation and Blood Coagulation

“…An increase in antibacterial activity and α-glucosidase inhibition were reported for hesperidin glycoside [ 11 ]. The O -glycosylation of resveratrol was reported to increase both its solubility in water and bioavailability while preventing oxidation [ 12 ]. The glycosylation of rutin has been extensively studied and is considered an efficient and available method to increase solubility [ 13 , 14 , 15 ]; however, information on the changes in its properties and efficacy is not fully understood.…”

A Comparative Study of Hesperetin, Hesperidin and Hesperidin Glucoside: Antioxidant, Anti-Inflammatory, and Antibacterial Activities In Vitro

“…In this study, hesperetin with high Log P value (poorly water soluble) showed high antibacterial activity against the Gram-positive and Gram-negative bacteria tested, but hesperidin glucoside, with very low Log P value (highly water soluble), also showed higher antibacterial activities than hesperidin with high Log P value. Lipophilicity of flavonoids is an important factor for antimicrobial activity, but high lipophilicity does not always lead to high antimicrobial activity in many cases [ 81 , 82 , 83 ]. In this study, 2% of DMSO did not sufficiently increase the solubility of hesperidin or hesperetin, and there were some precipitates in the bacterial culture broth at high concentration of hesperidin or hesperetin.…”

Resveratrol and cyclodextrins, an easy alliance: Applications in nanomedicine, green chemistry and biotechnology

“…1) 39 . Research has moved over the past few years toward the synthesis of their αanomeric counterparts whose aqueous solubility and surfactant properties are superior [163][164][165][166] .…”

“…The green synthesis of 3-O-α-D-glucosyl resveratrol with sucrose and not CDs as a glucose donor, has already been performed by a combination of an ionic liquid and a buffer, which considerably increases resveratrol solubility under the catalytic action of a phosphorylase from Bifidobacterium adolescentis 167 . Several works have reported achievement of stilbene O-glucosylation with cyclodextrin glucosyl-(glucano)-transferases (CGTases) from various sources as biocatalysts utilizing starch or CDs as glucose donors [163][164][165][166]168,169 (Table 4). CGTases have often been employed for the biosynthesis of various polyphenolic glucoside derivatives: epicatechin glucosides 170 , kaempferol glucoside 171 , genistein diglucoside 172 , flavonol and flavanones glucosides 173 , pinoresinol glucoside 174 or α-arbutin 175 .…”

“…As aforementioned, CDs allow the increasing of the internalization rate of compounds poorly soluble in water such as stilbene aglycones. Their use is thus particularly conducive to the green synthesis of stilbene glucoside derivatives 39,164,165 . The transfer of an α-glucoside group or more groups from the donor (the cyclodextrin) to the acceptor (the stilbene) may proceed through coupling of the cyclodextrin and the stilbene, which randomly attach to the active site of the CGTase 168,176 .…”