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

Significance Statement

Membrane Approach to Understand the Pleiotropic Effects of Resveratrol

Resveratrol is a natural polyphenol compound with great potential in the cancer therapy, cardiovascular protection, and neurodegenerative disorders. The mechanism of action of resveratrol may be associated to its capacity of modulating cell membrane structure and function, thereby influencing the activity of several membrane associating receptors, proteins and enzymes.

The present research reveals potential molecular interactions between resveratrol and lipid rafts found in cell membranes, bringing a new membrane approach to understand the pleiotropic effects of this phytochemical.

Förster resonance energy transfer (FRET), DPH fluorescence quenching by TEMPO, and Triton X-100 detergent resistance assay have been employed to monitor lipid phase separation in model membranes. Unilamellar liposomes composed of phosphatidylcholine, cholesterol and sphingomyelin were chosen as membrane mimetic systems.

The results indicate that resveratrol is able to incorporate in lipid bilayers, inducing phase separation, stabilizing and promoting the formation of ordered domains (lipid rafts) that can act as organizing centers for the assembly of proteins and receptors, which in turn may be involved in the cell signaling and cellular processes.

In conclusion, the influence of resveratrol on the regulation of lipid domains formation and stability provide a rational approach to better understand the therapeutic effects of this promising compound.

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

About The Author

Dr. Ana Rute Neves (PhD Pharmaceutical Sciences in 2015) is a Post-doctoral researcher in the Molecular Biophysics and Biotechnology Unit at GABAI/UCIBIO/REQUIMTE, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Portugal.

Her research focuses on biophysical and biochemical approaches to study the interaction of phytochemicals with biomembranes (using liposomes as biomimetic systems) in order to explain their therapeutic properties and the development of nanopharmaceuticals (lipid nanoparticles) as drug delivery systems to create new and more efficient therapies for a range of diseases.

About The Author

Dr. Cláudia Nunes (PhD Pharmaceutical Sciences in 2011) is a Post-doctoral researcher in the Molecular Biophysics and Biotechnology Unit at GABAI/UCIBIO/REQUIMTE, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Portugal.

Her research activities include the assessment of drug-membrane interactions, using membrane mimetic models; the development of nanotechnology based drug delivery systems (silica nanotubes, solid lipid nanoparticles, nanostructured lipid particles and liposomes) that can be efficiently carried to the inflamed tissues avoiding the gastric local toxic effects of the classical therapies.

About The Author

Professor Salette Reis (PhD Analytical Chemistry in 1995) is the Director of the Department of Chemical Sciences and the group leader of the Molecular Biophysics and Biotechnology Unit at GABAI/UCIBIO/REQUIMTE, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Portugal.

Her investigation has been focused in biophysics and pharmaceutical chemistry, namely in the use of biomimetic membrane models to study the effect of drugs on biological membranes trying to establish a relationship between this effect and their activity/mechanism of action; and the development of nanocarrier systems for drug delivery to overcome the disadvantages of the classical therapies.

Journal Reference

Biochim Biophys Acta. 2016;1858(1):12-8.  

Neves AR1, Nunes C1, Reis S2.

Show Affiliations
  1. UCIBIO, REQUIMTE, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal.
  2. UCIBIO, REQUIMTE, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal. Electronic address: [email protected]

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.

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