title: Therapeutic basis of glycyrrhizin on chronic hepatitis B.
abstract: Glycyrrhizin, a major component of a herb (licorice), has been intravenously used for the treatment of chronic hepatitis B in Japan and improves liver function with occasional complete recovery from hepatitis. This substance modifies the intracellular transport and suppresses sialylation of hepatitis B virus (HBV) surface antigen (HBsAg) in vitro. This study was designed to clarify the pharmacological basis for its effectiveness. The structure-bioactivity relationship of glycyrrhizin, glycyrrhetic acid 3-O-monoglucuronide and glycyrrhetic acid was determined, and glycyrrhetic acid was found to be the most active of them. The amounts of three substances bound to the liver were evaluated in guinea pigs after intravenous administration of glycyrrhizin. Glycyrrhizin and glycyrrhetic acid 3-O-monoglucuronide were detected at concentrations of 31.8-1.3 micrograms/g of liver, but glycyrrhetic acid was not detected. When glycyrrhizin attained these concentrations in the cellular fraction of the PLC/PRF/5 cell culture, it suppressed the secretion of HBsAg as reported previously. These results indicated that glycyrrhizin administered intravenously might bind to hepatocytes at the concentration at which glycyrrhizin could modify the expression of HBV-related antigens on the hepatocytes and suppress sialylation of HBsAg.
authors.affiliation: Department of Virology, Toyama Medical and Pharmaceutical University, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Sato
authors.forename: W
authors.initials: W
authors.lastname: Goto
authors.forename: J
authors.initials: J
authors.lastname: Yamamura
authors.forename: M
authors.initials: M
authors.lastname: Kurokawa
authors.forename: S
authors.initials: S
authors.lastname: Kageyama
authors.forename: T
authors.initials: T
authors.lastname: Takahara
authors.forename: A
authors.initials: A
authors.lastname: Watanabe
authors.forename: K
authors.initials: K
authors.lastname: Shiraki
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D019695:Glycyrrhizic Acid; D006168:Guinea Pigs; D006514:Hepatitis B Surface Antigens / Q000378:metabolism; D006515:Hepatitis B virus / Q000187:drug effects*; D006801:Humans; D008099:Liver / Q000378:metabolism; D015394:Molecular Structure; D014407:Tumor Cells, Cultured
chemical_list: D000998:Antiviral Agents; D006514:Hepatitis B Surface Antigens; D019695:Glycyrrhizic Acid; D006034:Glycyrrhetinic Acid