Modulation of peroxisome proliferator activated receptor gamma (PPARG) by Glycyrrhiza glabra

Glycyrrhiza glabra, commonly referred to as licorice root, is native to southern Europe and parts of Asia, but is currently grown throughout the world. It has been used for over 3000 years as a part of traditional medical treatments to soothe irritated membranes, to loosen congestion and stimulate mucous production. Scientific evidence supports its use as a gastric ulcer treatment. The root's major active compounds include glycyrrhizin (glycyrrhizic acid) and glabridin. Glycyrrhizin, a sweet-tasting compound has been linked to Licorice's deleterious side effects which include water retention and hypertension, a mineralocorticoid receptor agonist. Glabridin, structurally dissimilar to glycyrrhizin, has been shown to upregulate AMP-activated protein kinase to alleviate adipose tissue development in obese rodent models.

Peroxisome proliferator activated receptor gamma (PPARG) is a nuclear hormone receptor, currently under critical review for its impact on a number of anti-aging systems, including glucose utilization, inflammation and aberrant cell growth.

Here we describe a licorice extract that activates an isolated binding domain of peroxisome proliferator activated receptor gamma (PPARG) with an EC50 of 5 ug/ml. Bio-directed Fractionation in tandem with an LC/MSMS was used to identify glabridin not glycyrrhizin as the PPARG activating compound of Licorice. Glabridin activates PPARG and not peroxisome proliferator activated receptor alpha. Its activity is inhibited by a specific PPARG inhibitor. It activates the full-length receptor and subsequent PPAR response element containing reporter assay. Modulation of specific genetic targets are being evaluated. These data provide further information on the biological activity of Glycyrrhiza glabra.