EFFECTS OF GLYCYRRHIZIN ON HEPATITIS-B SURFACE-ANTIGEN - A BIOCHEMICAL AND MORPHOLOGICAL-STUDY

Glycyrrhizin, a major component of a herb (licorice), has been widely used to treat chronic hepatitis B in Japan. This substance improves li ver function with occasional complete recovery from hepatitis; its eff ects on the secretion of hepatitis B surface antigen (HBsAg) were exam ined in vitro. Glycyrrhizin suppressed the secretion of HBsAg and accu mulated it dose-dependently in PLC/PRF/5 cells. Its action was further analyzed and determined in the HBsAg-expression system using the vari cella-zoster virus. Glycyrrhizin suppressed the secretion of HBsAg, re sulting in its accumulation in the cytoplasmic vacuoles in the Golgi a pparatus area. HBsAg labeled with S-35-methionine and cysteine accumul ated in the cells and its secretion was suppressed dose-dependently in glycyrrhizin-treated culture. The secreted HBsAg was modified by N-li nked and O-linked glycans but its sialylation was inhibited dose-depen dently by glycyrrhizin. Thus glycyrrhizin suppressed the intracellular transport of HBsAg at the trans-Golgi area after O-linked glycosylati on and before its sialylation. HBsAg particles were mainly observed on the cell surface in the glycyrrhizin-treated culture but not in the u ntreated culture. This suggests that asialylation of HBsAg particles r esulted in the novel surface nature of glycyrrhizin-treated HBsAg part icles. We elucidated the unique mechanism of action of glycyrrhizin on HBsAg processing, intracellular transport, and secretion. (C) Journal of Hepatology.