title: Spectroscopic and molecular dynamics characterization of glycyrrhizin membrane-modifying activity.
abstract: Glycyrrhizic acid (GA) is a triterpene glycoside extracted from licorice root. Due to its amphiphilicity GA is capable of forming complexes with a variety of hydrophobic molecules, substantially increasing their solubility. GA can enhance the therapeutic effects of various drugs. It was hypothesized that the increased bioavailability of the drug by GA is not only due to increased solubility, but also to enhancement of drug permeability through cell membranes. In this study the interaction of GA with POPC liposomes and model DOPC, POPC and DPPC bilayers was investigated by NMR with addition of shift reagents and MD simulations. This work helps to better understand the mechanism of enhanced drug bioavailability in the presence of GA. NMR and MD reveal that GA does penetrate into the lipid bilayer. NMR shows that GA changes the mobility of lipids. GA is predominantly located in the outer "half-layer" of the liposome and that the middle of the hydrophobic tails is the preferred location. GA freely passes through the bilayer surface to the inner part bringing a few water molecules. Also both approaches indicate pore formation in the presence of GA. The GA interaction with membranes is an additional aspect of the biological activity of GA-based drug delivery systems.
authors: Institute of Chemical Kinetics and Combustion, Institutskaya St., 3, 630090, Novosibirsk, Russia; Novosibirsk State University, Pirogova St., 2, 630090, Novosibirsk, Russia. Electronic address: olga.gluschenko@gmail.com.
authors: O Yu
authors: OY
authors: Selyutina
authors: Institute of Chemical Kinetics and Combustion, Institutskaya St., 3, 630090, Novosibirsk, Russia; Novosibirsk State University, Pirogova St., 2, 630090, Novosibirsk, Russia.
authors: I E
authors: IE
authors: Apanasenko
authors: Institute of Chemical Kinetics and Combustion, Institutskaya St., 3, 630090, Novosibirsk, Russia.
authors: A V
authors: AV
authors: Kim
authors: Institute of Chemical Kinetics and Combustion, Institutskaya St., 3, 630090, Novosibirsk, Russia; Novosibirsk State University, Pirogova St., 2, 630090, Novosibirsk, Russia.
authors: E A
authors: EA
authors: Shelepova
authors: Nesmeyanov Institute of Organoelement Compounds of Russian Academy of Sciences, Vavilova St., 28, 119334, Moscow, Russia.
authors: S S
authors: SS
authors: Khalikov
authors: Institute of Chemical Kinetics and Combustion, Institutskaya St., 3, 630090, Novosibirsk, Russia.
authors: N E
authors: NE
authors: Polyakov
mesh_terms: D002462:Cell Membrane / Q000737:chemistry*; D019695:Glycyrrhizic Acid / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D008051:Lipid Bilayers / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D056004:Molecular Dynamics Simulation; D010713:Phosphatidylcholines / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D008051:Lipid Bilayers; D008081:Liposomes; D010713:Phosphatidylcholines; D019695:Glycyrrhizic Acid
keywords: Drug delivery; Glycyrrhizic acid; Lipid bilayer; Liposome; Membrane permeability; Molecular dynamics; Nuclear magnetic resonance