Resveratrol induces ordered domains formation in biomembranes: Implication for its pleiotropic action

Abstract

Resveratrol is a polyphenol compound with great value in cancer therapy, cardiovascular protection, and neurodegenerative disorders. The mechanism by which resveratrol exerts such pleiotropic effects is not yet clear and there is a huge need to understand the influence of this compound on the regulation of lipid domains formation on membrane structure. The aim of the present study was to reveal potential molecular interactions between resveratrol and lipid rafts found in cell membranes by means of Förster resonance energy transfer, DPH fluorescence quenching, and triton X-100 detergent resistance assay. Liposomes composed of egg phosphatidylcholine, cholesterol, and sphingomyelin were used as model membranes. The results revealed that resveratrol induces phase separation and formation of liquid-ordered domains in bilayer structures. The formation of such tightly packed lipid rafts is important for different signal transduction pathways, through the regulation of membrane-associating proteins, that can justify several pharmacological activities of this compound.

Resveratrol Inhibits Porcine Intestinal Glucose and Alanine Transport: Potential Roles of Na+/K+-ATPase Activity, Protein Kinase A, AMP-Activated Protein Kinase and the Association of Selected Nutrient Transport Proteins with Detergent Resistant Membranes

“…Effects of RSV on Ca 2+ channels and signaling [ 44 , 45 ] and K + channels [ 46 , 47 ] have already been described in several studies. One link between the formation of AKAP/PKA signaling complexes and RSV may be the association of AKAPs and adenylate cyclase with lipid rafts [ 40 , 48 ] and the ability of RSV to influence the properties of bio membranes including lipid raft formation [ 33 , 34 , 35 ]. We investigated whether RSV changes the association of intestinal nutrient transporters with DRMs.…”

“…3. Since Resveratrol is known to affect membrane properties and influences the formation of detergent resistant membrane fractions (DRM) [ 32 , 35 ], the association of nutrient transport proteins with DRMS and therefore their activity may be changed by Resveratrol.…”

“… RSV is known to affect membrane properties by accumulating in the outer leaflet of the lipid bilayer [ 32 ] or in DRMs and one way to enter the cell is via raft-dependent endocytosis [ 33 , 34 ]. There is also evidence that RSV influences the formation of lipid rafts [ 35 ], which might be associated with the variety of effects that are exhibited by RSV. …”

Molecular Mechanism of Resveratrol’s Lipid Membrane Protection

“…The position of resveratrol within the bilayer has also been discussed as concentration dependent 18 . Besides the location, the effects of resveratrol on the structure and fluidity of the lipid bilayer, it has been reported that resveratrol resembles cholesterol action on DMPC membrane and membrane models consisting of a mixture of egg-phosphatidyl choline, cholesterol, and sphingomyelin 6 , 21 , 22 .…”

Clinical efficacy of resveratrol as an adjuvant with meloxican in the treatment of knee osteoarthritis patients: A double-blind, randomised, placebo-controlled trial

“…In this regard, numerous studies have recently focused on the potential effects of natural compounds, including nutraceuticals, to halt the progression of OA and reduce any associated symptoms (Hussain et al, 2009;Moura et al, 2016). Resveratrol is a natural polyphenol extracted from Polygonum cuspidatum, which shows pleiotropic properties that suggest it may be applied for many therapeutic uses, including the treatment of cancer, cardiovascular diseases, and metabolic disorders (Neves, Nunes, Reis, 2016). Meanwhile, many preclinical studies have revealed the anti-inflammatory properties of resveratrol that might enable the degenerative articular damage to be ameliorated in vitro and in experimental animals (Jiang et al, 2017;Ma et al, 2015).…”