Metabolites identification of glycyrin and glycyrol, bioactive coumarins from licorice.

Coumarins are an important group of bioactive constituents in licorice (Glycyrrhiza uralensis), a worldwide popular herbal medicine. This study aims to elucidate the metabolism of two major licorice coumarins, glycyrin and glycyrol in rats. After oral administration of 40mg/kg glycyrin, neither the parent compound nor its metabolites could be detected in rats plasma or urine samples, indicating that glycyrin had poor oral bioavailability. Two hydroxylated metabolites, 4″-hydroxyl glycyrin and 5″-hydroxyl glycyrin, were detected in rat liver microsome incubation system. Among them, the major metabolite 4″-hydroxyl glycyrin, which is a new compound, was obtained by microbial transformation of Syncephalastrum racemosum AS 3.264. Its structure was fully identified by 1D and 2D NMR. Meanwhile, glycyrol, together with three metabolites, were detected in rats urine and fecal samples after oral administration (40mg/kg). Their structures were tentatively characterized by LC/MS. Glycyrol mainly undertakes hydroxylation metabolism, accompanied by hydration and dehydrogenation as minor reactions. This is the first systematic study on metabolism of glycyrin and glycyrol. The results could be valuable to evaluate druggability of these bioactive natural products.