Licorice: From Pseudohyperaldosteronism to Therapeutic Uses

Abstract

Licorice has been used as a medicinal plant from 2.500 years. It shows a wide range of biological and pharmacological activities, including anti-inflammatory and immune regulatory actions. One of its most known effects is the induction of hypertension, and it can induce what appears to be pseudohyperaldosteronism, due to glycyrrhetinic acid, the main active component of the root. Glycyrrhetinic acid and metabolites block the 11 beta-hydroxysteroid dehydrogenase type 2 and also bind mineralocorticoid receptors directly, acting as agonists. However, other interesting therapeutic uses of licorice are linked to its anti-androgen and estrogen-like activity, especially in the treatment of polycystic ovary syndrome (PCOS) in conjunction with spironolactone therapy. In this brief review, we report the main features and possible therapeutic uses of this ancient plant.

Keywords: aldosterone; glycyrrhetinic acid (GA); hypertension; inflammation; licorice; polycystic ovary syndrome (PCOS); pseudohyperaldosteronism.

Figure 1

Endocrine effects of the main components of licorice. GI, glycyrrhizic acid; GA, glycyrrhetinic acid; 11HSD2, 11 beta-hydroxysteroid dehydrogenase 2; MR, mineralocorticoid receptor; 17HSD, 17 hydroxysteroid dehydrogenase; ER, estrogen receptor.

Figure 2

Mechanism of conversion of cortisol into cortisone through 11 beta-hydroxysteroid dehydrogenase 2 (11HSD2). This enzyme is a NAD-dependent dehydrogenase enzyme, mainly expressed in the kidney, intestine, salivary and sweat glands. It can be inhibited by glycyrrhetinic acid, leading to functional mineralocorticoid excess due to unmetabolized cortisol at the level of classical target tissues of aldosterone.

Figure 3

Red blood cell (RBC) membrane alterations induced by oxidative stress and the possible anti-inflammatory effect of licorice. Glycyrrhetinic acid (GA), which has been shown to directly interact with membrane sphingolipids and cholesterol, can induce a protective shield against membrane protein oxidation, mainly avoiding protein band 3, the main constituents of RBC membranes, from being oxidized by ROS to form high molecular weight aggregate (HMWA), recognized by circulating IgG as premature aged cells. GA also prevents protein glutathionylation, which would avoid cytosolic GSH store depletion and support the correct functioning of cytosolic enzymes such as Carbonic Anhydrase (CA2).