Glycyrrhizin-induced changes in phospholipid dynamics studied by 1H NMR and MD simulation.

Phospholipid bilayer constitutes the basis of the cell membrane. Any changes in its structure and dynamics could significantly affect the properties and functions of the cell membrane and associated proteins. It could, in its turn, affect the mechanism and strength of drug-membrane interaction. Phase transitions in lipid bilayer play an important role in cell life and in transmembrane transport of ions and drug molecules. In the present study we have tried to clarify the mechanism of glycyrrhizin bioactivity by the study of its influence on the lipid dynamics and phase transition of the lipid bilayer. For this purpose, a combination of nuclear magnetic resonance (NMR) and molecular dynamic (MD) simulations was used. Glycyrrhizin is the saponin extracted from licorice root. It displays a wide spectrum of biological activity and is frequently used in traditional medicine since ancient times. Now glycyrrhizin attracts additional attention as a novel multifunctional drug delivery system. We have established that glycyrrhizin interaction with dipalmitoylphosphatidylcholine lipid bilayers leads to changes in lipid mobility and phase transition temperature. NMR and MD results demonstrated that a glycyrrhizin molecule is able to integrate into a lipid bilayer and form stable aggregates inside. We hypothesize that surface curvatures caused by local changes in the lipid composition and the presence of phase boundaries might affect the permeability of the cell membrane.