Novel Mechanism Supporting Therapeutic Effects of Glycyrrhizin in Acute or Chronic Hepatitis

Abstract

Glycyrrhizin (GL) isolated from the roots of licorice plant (Glycyrrhiza glabra L.) has been traditionally used for treating peptic ulcer, hepatitis, and pulmonary bronchitis. In addition to the protective efects of GL against liver injury or cancer proliferation by the membrane stabilization or via progesterone-receptor membrane component 1 (PGRMC1), the present chapter reports its new therapeutic mechanism through high-mobility group protein 1 (HMGB1) to which GL directly binds. In this study, we evaluated inlammation-promoting activity of HMGB1 and blockade of extracellular release of HMGB1 by GL in lipopolysaccharide (LPS)/d-galactosamine (GalN)-triggered mouse liver injury. In this experimental hepatitis model, apoptotic response of hepatocytes through the binding of HMGB1 protein to Glutathione transferase omega 1 (Gsto1), an apoptosis-associated gene, promoter region is caused, serum AST and ALT activities signiicantly increased, and GL-treatment prevented the apoptosis and inlammatory iniltrates induced with LPS/GalN-injection by disturbing the binding of HMGB1 protein to Gsto1 promoter sequence. Analysis with chromatin immunoprecipitation (ChIP)-assay revealed inhibiting the binding of HMGB1 protein to Gsto1 by the binding of GL to HMGB1.