glycyrrhetinic

Glycyrrhetinic, commonly encountered as glycyrrhetinic acid, is the aglycone of glycyrrhizin, the major sweet-tasting constituent of licorice root (Glycyrrhiza glabra). It is a lipophilic triterpenoid that occurs in licorice extracts used in traditional medicine and various commercial preparations.

Chemistry and sources: Glycyrrhetinic acid is a pentacyclic triterpenoid obtained by hydrolysis of glycyrrhizin. As the aglycone, it represents the non-sugar portion of the licorice glycoside and is often present in the non-saponin fractions of licorice extracts.

Pharmacology: The principal mechanism is inhibition of 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2). Inhibition allows cortisol to activate mineralocorticoid receptors in the kidney, promoting sodium retention, potassium loss, and hypertension. This can lead to edema and hypokalemia, particularly with high or long-term intake. Glycyrrhetinic acid also exhibits anti-inflammatory properties and has been explored for topical dermatological and antimicrobial effects in vitro, though clinical uses focus largely on licorice-derived products.

Uses and safety: In topical dermatology and some cosmetics, glycyrrhetinic acid derivatives are used for anti-inflammatory effects and to support skin conditioning. Oral licorice preparations containing glycyrrhizin and glycyrrhetinic acid carry a risk of pseudoaldosteronism, and long-term or high-dose use is cautioned, especially in individuals with hypertension, kidney impairment, or heart failure. Interactions with corticosteroids, diuretics, and other antihypertensives may occur.

Notes: Glycyrrhetinic acid is the aglycone component of glycyrrhizin and is studied for various pharmacological activities, but its cardiovascular risk profile requires careful consideration in licorice-derived products.