Affinity of liquorice derivatives for mineralocorticoid and glucocorticoid receptors

Abstract

Liquorice abuse causes a syndrome of pseudohyperaldosteronism. Much less commonly, glucocorticoid-like effects have been reported. The electrolyte-active principle of liquorice is glycyrrhizic acid (GI), which can be hydrolyzed to glycyrrhetinic acid (GE). Previous studies have reported that GE, but not GI, may occupy mineralocorticoid and glucocorticoid receptors. We here report that both GE and GI can bind to both mineralocorticoid and glucocorticoid receptors. The affinity of GI for mineralocorticoid receptors is four orders of magnitude lower than aldosterone and for glucocorticoid receptors five orders of magnitude lower than dexamethasone. The affinity, though low, is sufficient to explain the mineralocorticoid-like side effects, given the large amount of liquorice required to produce such a syndrome.