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 liver function with occasional complete recovery from hepatitis; its effects on the secretion of hepatitis B surface antigen (HBsAg) were examined in vitro. Glycyrrhizin suppressed the secretion of HBsAg and accumulated it dose-dependently in PLC/PRF/5 cells. Its action was further analyzed and determined in the HBsAg-expression system using the varicella-zoster virus. Glycyrrhizin suppressed the secretion of HBsAg, resulting in its accumulation in the cytoplasmic vacuoles in the Golgi apparatus area. HBsAg labeled with 35S-methionine and cysteine accumulated in the cells and its secretion was suppressed dose-dependently in glycyrrhizin-treated culture. The secreted HBsAg was modified by N-linked and O-linked glycans but its sialylation was inhibited dose-dependently by glycyrrhizin. Thus glycyrrhizin suppressed the intracellular transport of HBsAg at the trans-Golgi area after O-linked glycosylation and before its sialylation. HBsAg particles were mainly observed on the cell surface in the glycyrrhizin-treated culture but not in the untreated culture. This suggests that asialylation of HBsAg particles resulted in the novel surface nature of glycyrrhizin-treated HBsAg particles. We elucidated the unique mechanism of action of glycyrrhizin on HBsAg processing, intracellular transport, and secretion.
Takahara
T
T
Third Department of Internal Medicine, Toyama Medical and Pharmaceutical University, Japan.
Watanabe
A
A
Shiraki
K
K
D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D019695:Glycyrrhizic Acid; D006509:Hepatitis B / Q000188:drug therapy; D006514:Hepatitis B Surface Antigens / Q000096:biosynthesis / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D008854:Microscopy, Electron; D016253:Microscopy, Immunoelectron; D014407:Tumor Cells, Cultured
D000998:Antiviral Agents; D006514:Hepatitis B Surface Antigens; D019695:Glycyrrhizic Acid; D006034:Glycyrrhetinic Acid