TY - JOUR

T1 - Effect of Glycyrrhizic Acid and Arabinogalactan on the Membrane Potential of Rat Thymocytes Studied by Potential-Sensitive Fluorescent Probe

AU - Glazachev, Yuri I.

AU - Schlotgauer, Anna A.

AU - Timoshnikov, Viktor A.

AU - Kononova, Polina A.

AU - Selyutina, Olga Yu

AU - Shelepova, Ekaterina A.

AU - Zelikman, Maxim V.

AU - Khvostov, Mikhail V.

AU - Polyakov, Nikolay E.

PY - 2020/8/1

Y1 - 2020/8/1

N2 - The effect of the natural saponin glycyrrhizic acid (GA) and polysaccharide arabinogalactan (AG) on the transmembrane potential of rat thymocytes was investigated using the potential-sensitive fluorescent probe 4-(p-dimethylaminostyryl)-1-methylpyridinium (DSM). Incubation of cells with GA in micellar form resulted in a decrease of the amplitude of observed fluorescence kinetics that points out to a decrease of the transmembrane potential. The proposed mechanism is an increase of membrane ion permeability (passive ion transport) of the plasma cell membrane due to GA incorporation. The incorporation of GA molecules into the cell membrane is extremely sensitive to the degree of GA dissociation. The neutral form of glycyrrhizic acid enters the lipid bilayer in contrast to the deprotonated anionic form. The incubation of rat thymocytes with anionic form of GA, namely with its disodium salt, has no effect on the fluorescence kinetics. The possible reasons of this phenomenon are discussed in the light of the nuclear magnetic resonance (NMR) and molecular dynamics (MD) data. The treatment of thymocytes with AG affects only the initial rate of the probe incorporation. The proposed mechanism is that AG covers the surface of the cell membrane and forms a barrier for the probe. Additionally, our experiments demonstrated that both polysaccharide AG and GA in the neutral form (but not Na 2GA) effectively capture the cationic probe in an aqueous solution and then deliver it to the cell membrane.

AB - The effect of the natural saponin glycyrrhizic acid (GA) and polysaccharide arabinogalactan (AG) on the transmembrane potential of rat thymocytes was investigated using the potential-sensitive fluorescent probe 4-(p-dimethylaminostyryl)-1-methylpyridinium (DSM). Incubation of cells with GA in micellar form resulted in a decrease of the amplitude of observed fluorescence kinetics that points out to a decrease of the transmembrane potential. The proposed mechanism is an increase of membrane ion permeability (passive ion transport) of the plasma cell membrane due to GA incorporation. The incorporation of GA molecules into the cell membrane is extremely sensitive to the degree of GA dissociation. The neutral form of glycyrrhizic acid enters the lipid bilayer in contrast to the deprotonated anionic form. The incubation of rat thymocytes with anionic form of GA, namely with its disodium salt, has no effect on the fluorescence kinetics. The possible reasons of this phenomenon are discussed in the light of the nuclear magnetic resonance (NMR) and molecular dynamics (MD) data. The treatment of thymocytes with AG affects only the initial rate of the probe incorporation. The proposed mechanism is that AG covers the surface of the cell membrane and forms a barrier for the probe. Additionally, our experiments demonstrated that both polysaccharide AG and GA in the neutral form (but not Na 2GA) effectively capture the cationic probe in an aqueous solution and then deliver it to the cell membrane.

KW - Arabinogalactan

KW - Drug delivery

KW - Glycyrrhizic acid

KW - Membrane potential

KW - Thymocytes

KW - DRUG

KW - CELLS

KW - OLIGOSACCHARIDES

KW - TRANSDERMAL DELIVERY

KW - BIOAVAILABILITY

KW - PERMEABILITY TRANSITION

KW - BETA-CYCLODEXTRIN

KW - DYNAMICS

KW - FORCE-FIELD

KW - POLYSACCHARIDE ARABINOGALACTAN

UR - http://www.scopus.com/inward/record.url?scp=85088957806&partnerID=8YFLogxK

U2 - 10.1007/s00232-020-00132-3

DO - 10.1007/s00232-020-00132-3

M3 - Article

C2 - 32725429

AN - SCOPUS:85088957806

VL - 253

SP - 343

EP - 356

JO - Journal of Membrane Biology

JF - Journal of Membrane Biology

SN - 0022-2631

IS - 4

ER -