β-Glucuronidase Inhibitory Activity and Hepatoprotective Effect of 18β-Glycyrrhetinic Acid from the Rhizomes of Glycyrrhiza uralensis

An inhibitor of beta-glucuronidase from the rhizomes of Glycyrrhiza uralensis was isolated and its hepatoprotective activity on CCI4-induced hepatotoxicity of rats was investigated. From the water-soluble extract of G. uralensis, glycyrrhizin was isolated as a potent inhibitor of beta-glucuronidase. When glycyrrhizin was orally administered, it had a hepatoprotective activity. However, when glycyrrhizin was intraperitoneally administered, it did not have a hepatoprotective activity. 18 beta-Glycyrrhetinic acid, which is a major metabolite of glycyrrhizin by human intestinal bacteria, was also a potent inhibitor of beta-glucuronidase. When 18 beta-glycyrrhetinic acid was intraperitoneally administered, it also had some hepatoprotective activity. These results suggest that glycyrrhizin may be a natural prodrug for the observed hepatoprotective effect in rats and that serum beta-glucuronidase levels have implications for the liver injury, as reductions of its activity by administration of inhibitors such as G. uralensis or its derived products and silymarin correlate with reductions in biochemical indices of liver injury.