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.

Severe hypernatremia is defined as serum sodium levels above 152 mEq/L, with a mortality rate ≥60%. 85-year-old gentleman was brought to the emergency room with altered level of consciousness after refusing to eat for a week at a skilled nursing facility. On admission patient was nonverbal with stable vital signs and was responsive only to painful stimuli. Laboratory evaluation was significant for serum sodium of 188 mmol/L and water deficit of 12.0 L. Patient was admitted to medicine intensive care unit and after inadequate response to suboptimal fluid repletion, hemodialysis was used to correct hypernatremia. Within the first fourteen hours, sodium concentration only changed 1 mEq/L with a fluid repletion; however, the concentration dropped greater than 20 mEq/L within two hours during hemodialysis. Despite such a drastic drop in sodium concentration, patient did not develop any neurological sequela and was at baseline mental status at the time of discharge.

Prior EPR oximetry work by Subczynski and colleagues has shown that cholesterol increases membrane resistance to oxygen permeation by 3-to 5-fold when present in a 1:1 ratio with phospholipid. In the current study, we use molecular dynamics simulations to investigate the biophysics of oxygen transport in membranes incorporating cholesterol. The simulations enable cross-validation of the EPR oximetry measurements and the simulations. Further, we have been able to observe oxygen transport near the bilayer surface, which has not been accessible to EPR spin-label probes. We find excellent agreement between the simulation and EPR observations. Our simulations affirm that cholesterol reduces oxygen flux when present at a 1:1 ratio with phospholipid. They further indicate that the bilayer surface in the presence or absence of cholesterol presents greater resistance to permeation than previously observed by EPR.