THERAPEUTIC BASIS OF GLYCYRRHIZIN ON CHRONIC HEPATITIS-B

Glycyrrhizin, a major component of a herb (licorice), has been intrave nously used for the treatment of chronic hepatitis B in Japan and impr oves liver function with occasional complete recovery from hepatitis. This substance modifies the intracellular transport and suppresses sia lylation of hepatitis B virus (HBV) surface antigen (HBsAg) in vitro. This study was designed to clarify the pharmacological basis for its e ffectiveness. The structure-bioactivity relationship of glycyrrhizin, glycyrrhetic acid 3-O-monoglucuronide and glycyrrhetic acid was determ ined, and glycyrrhetic acid was found to be the most active of them. T he amounts of three substances bound to the liver were evaluated in gu inea pigs after intravenous administration of glycyrrhizin. Glycyrrhiz in and glycyrrhetic acid 3-O-monoglucuronide were detected at concentr ations of 31.8-1.3 mu g/g of liver, but glycyrrhetic acid was not dete cted. 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 glycyrrhiz in administered intravenously might bind to hepatocytes at the concent ration at which glycyrrhizin could modify the expression of HBV-relate d antigens on the hepatocytes and suppress sialylation of HBsAg.