Licorice Inhibits Corticosteroid 1lβ-Dehydrogenase of Rat Kidney and Liver:<i>In Vivo</i>and<i>in Vitro</i>Studies*

TLDR

Licorice’s active component glycyrrhetinic acid mimics excess mineralocorticoid secretion in humans. The study tests whether inhibition of 11β‑dehydrogenase, rather than mineralocorticoid receptor activation, underlies licorice‑induced pseudoaldosteronism. Oral glycyrrhizic acid partially inhibited renal 11β‑dehydrogenase in rats, and both glycyrrhetinic acid and carbenoxolone dose‑dependently blocked corticosterone conversion in kidney preparations, with no effect on 11‑oxoreductase, indicating that licorice’s pharmacology is driven by 11β‑dehydrogenase inhibition rather than mineralocorticoid receptor interaction.

Abstract

In humans, glycyrrhetinic acid (GE), the active pharmacological ingredient of licorice, produces symptoms resembling those caused by excess mineralocorticoid secretion. We are proposing that llft-dehydrogenase inhibition, and not intrinsic mineralocorticoid activity, is the primary mechanism of licorice-induced pseudoaldosteronism. Glycyrrhizic acid (glycyrrhetinic acid glucuronide), when given orally to rats, partially inhibited renal lljS-dehydrogenase. In rats treated with dexamethasone before glycyrrhizic acid administration there was similar enzyme inhibition, suggesting that antimineralocorticoid effects of dexamethasone in licorice excess states are not mediated through a direct effect on 11/3-dehydrogenase activity. Dispersed renal proximal tubular preparations, kidney homogenates, and microsomes readily converted corticosterone to 11-dehydrocorticosterone. GE and its synthetic analog carbenoxolone inhibited the conversion in these systems in a dose-dependent manner. Corticosteroid 11-oxoreductase, which was present in kidney homogenates at a level 10–20% that of 11β-dehydrogenase was not inhibited by any of the agents. With homogenate and microsomes, the K; of GE was about 10−9-10−8 M; with intact tubules, the K, of GE was about 10−5-10−6 M. It is suggested that a permeability barrier slows the entry of GE into the tubule cells. We conclude that the effects of licorice on corticosteroid metabolism in the kidney are based on its inhibition of 11β-dehydrogenase. Our data, supplemented by published evidence, is inconsistent with the conclusion that interaction with mineralocorticoid receptors accounts for the pharmacological effects of GE.