3-Monoglucuronyl-glycyrrhetinic acid is a major metabolite that causes licorice-induced pseudoaldosteronism.
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.
Kato
H
H
First Department of Internal Medicine, Toyama Medical and Pharmaceutical University, Japan.
Kanaoka
M
M
Yano
S
S
Kobayashi
M
M
D042842:11-beta-Hydroxysteroid Dehydrogenases; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006034:Glycyrrhetinic Acid / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology; D006035:Glycyrrhiza / Q000378:metabolism*; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D006913:Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors*; D006929:Hyperaldosteronism / Q000139:chemically induced* / Q000175:diagnosis; D007668:Kidney / Q000648:ultrastructure; D008297:Male; D008861:Microsomes / Q000201:enzymology; D008875:Middle Aged; D009249:NADP / Q000494:pharmacology; D010946:Plants, Medicinal
C052400:glycyrrhetyl 3-monoglucuronide; D009249:NADP; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases; D006034:Glycyrrhetinic Acid; D006854:Hydrocortisone