Effect of glycyrrhizin and its derivatives on integrity of human red blood cells

Abstract

Introduction: The first and most prevailing cells that glycyrrhizin (GL) and glycyrrhetinic acid (GA) encounter are red blood cells (RBCs). However, what follows this event is poorly understood. This study aims to evaluate the effect of GL and its derivatives on the integrity of human RBCs. Methods: The integrity of human RBC was assessed under normal isotonic conditions and following osmotic and nystatin-induced colloid-osmotic stress by measuring the amount of hemoglobin released. The pore size was determined by the osmotic protection method. Results: GL was found to be virtually non-hemolytic. However, removal of the carbohydrate moiety of GL imparted significant RBC lytic activity to the cis-(beta-) but not to the trans-(alpha-) isoform of GA. The hemisuccinate radical at position C3 (carbenoxolone) greatly diminished the hemolytic property of GA. The RBC lysis occurred by colloid-osmotic mechanism due to the formation of hydrophilic pores with the radius of ~2.3 nm. At the sublytic doses, the two stereo-isoforms displayed opposite effects on the osmo-resistivity of human RBC: osmoprotection for alpha-GA and osmotic sensibilization for beta-GA. Similar osmotic sensibilization was also observed for GL and carbenoxolone. The two stereo-isoforms exhibited different but not opposite weakening effects on the resistivity of the RBC to the colloid-osmotic stress induced by nystatin, a pore-former. The weakening effect was found intermediate for GL and absent for carbenoxolone. Conclusion: Upon intestinal digestion and absorption, depending on the structure and dosage, the GL hydrolysis products interact with RBC with both beneficial and detrimental consequences.

Effect of pinocembrin on thymocyte proliferation and death

“…The well-known antioxidant properties of pinocembrin (30,39) could be related to the pinocembrin's protective effects against necrosis, e.g., by suppressing the lipid peroxidation which labializes the lipid matrix of the cellular membrane. We hypothesize that similar to gossypol (36) as well as to glycyrrhizic acid and its derivatives (40), pinocembrin may intercalate into the bilayer lipid matrix of the thymocyte plasma membrane and enhance its rigidity and resistivity towards the mechanical distortion.…”