3-Monoglucuronyl-glycyrrhetinic acid is a major metabolite that causes licorice-induced pseudoaldosteronism.

Abstract

18 beta-Glycyrrhetinic acid (GA) has been thought to be one of the major metabolites that causes licorice-induced pseudoaldosteronism. However, we found no difference in the blood level of GA between the patients with and without pseudoaldosteronism. We measured the blood concentration of 3 beta-D-(monoglucuronyl)18 beta-glycyrrhetinic acid (3MGA), another metabolite of 3 beta-D-diglucuronyl-18 beta-glycyrrhetinic acid (glycyrrhizin), by high performance liquid chromatography and found an increased concentration of 3MGA in 10 patients with licorice-induced pseudoaldosteronism, but not in 11 patients without pseudoaldosteronism. To investigate whether 3MGA can inhibit 11 beta-hydroxysteroid dehydrogenase, we incubated rat renal microsome with or without 3MGA and measured the conversion rate of [3H]cortisol to [3H]cortisone. 3MGA was found to be a potent inhibitor of 11 beta-hydroxysteroid dehydrogenase, allowing cortisol to exert its full mineralocorticoid effects. These results suggest that licorice-induced pseudoaldosteronism is due to an increased concentration of 3MGA, but not GA, in the circulating blood of these patients.