beta-glucuronidase inhibitory activity and hepatoprotective effect of 18 beta-glycyrrhetinic acid from the rhizomes of Glycyrrhiza uralensis

An inhibitor of beta-glucuronidase from the rhizomes of Glycyrrhiza uralens is was isolated and its hepatoprotective activity on CCl4-induced hepatotox icity of rats was investigated. From the water-soluble extract of G. urolen sis, glycyrrhizin was isolated as a potent inhibitor of beta-glucuronidase. When glycyrrhizin was orally administered, it had a hepatoprotective activ ity. 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 activ ity. These results suggest that glycyrrhizin may be a natural prodrug for t he observed hepatoprotective effect in rats and that serum beta-glucuronida se levels have implications for the liver injury, as reductions of its acti vity by administration of inhibitors such as G. uralensis or its derived pr oducts and silymarin correlate with reductions in biochemical indices of li ver injury.