Molecular Mechanism of Resveratrol’s Lipid Membrane Protection

Resveratrol, a natural compound found in red wine and various vegetables, has drawn increasing interest due to its reported benefit in cardiovascular protection, neurodegenerative disorders, and cancer therapy. The mechanism by which resveratrol exerts such pleiotropic effects remains unclear. It re...

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Bibliographic Details
Published in:Scientific reports 2018-01, Vol.8 (1), p.1587-12, Article 1587
Main Authors: Fei, Qinqin, Kent, David, Botello-Smith, Wesley M., Nur, Fariah, Nur, Saadia, Alsamarah, Abdelaziz, Chatterjee, Payal, Lambros, Maria, Luo, Yun
Format: Article
Language:English
Subjects:
119/118
631/57/2266
631/57/2270
Cancer
Cholesterol
Drug development
Free energy
Humanities and Social Sciences
Hydrogen Bonding
Lecithin
Lipid Bilayers - metabolism
Lipids
Molecular dynamics
Molecular Dynamics Simulation
multidisciplinary
Neurodegenerative diseases
Phosphatidylcholine
Phospholipase A1
Phospholipase A2
Polyphenols
Resveratrol
Science
Science (multidisciplinary)
Stilbenes - chemistry
Stilbenes - metabolism
Vegetables
Wine
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Summary:Resveratrol, a natural compound found in red wine and various vegetables, has drawn increasing interest due to its reported benefit in cardiovascular protection, neurodegenerative disorders, and cancer therapy. The mechanism by which resveratrol exerts such pleiotropic effects remains unclear. It remains as one of the most discussed polyphenol compounds in the debating "French Paradox". In this study, using molecular dynamics simulations of dipalmitoyl phosphatidylcholine (DPPC) bilayer with resveratrol, we generated a free energy map of resveratrol’s location and orientation of inside the lipid bilayer. We found that resveratrol increases the surface area per lipid and decreases membrane thickness, which is the opposite effect of the well-studied cholesterol on liquid phase DPPC. Most importantly, based on the simulation observation that resveratrol has a high probability of forming hydrogen bonds with sn-1 and sn-2 ester groups, we discovered a new mechanism using experimental approach, in which resveratrol protects both sn-1 and sn-2 ester bonds of DPPC and distearoyl phosphatidylcholine (DSPC) from phospholipase A1 (PLA1) and phospholipase A2 (PLA2) cleavage. Our study elucidates the new molecular mechanism of potential health benefits of resveratrol and possibly other similar polyphenols and provides a new paradigm for drug design based on resveratrol and its analogs.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-017-18943-1