Differences in the metabolism of glycyrrhizin, glycyrrhetic acid and glycyrrhetic acid monoglucuronide by human intestinal flora.

Glycyrrhizin (1.0 mm GL), glycyrrhetic acid (1.0 mm GA) and glycyrrhetic acid monoglucuronide (1.0 mM GAMG), as well as a combination of all components added to medium at the start of growth and at the maximal stage of intestinal flora were cultured for 24 and 12 h, respectively. GL alone enhanced GL beta-D-glucuronidase activity about 2.7- to 6.8-fold and was metabolized to between 55 and almost 100% GA. GAMG alone was metabolized to almost 100% GA by GAMG beta-D-glucuronidase activity. Intestinal flora grown to a maximal stage converted GL to about 15% GA and GAMG to about 13% GA at almost 0 h. GL in combined GL and GA was consumed about 20% at 12 h and about 100% at 24 h under different culture conditions. Metabolite GA and unchanged GA were metabolized to a negligible amount of 3-oxoglycyrrhetic acid, 3alpha-hydroxyglycyrrhetic acid (3alpha-hydroxyGA) or both by 3beta-hydroxysteroid dehydrogenase and 3alpha-hydroxyGA dehydrogenase activities. Combined GL and GAMG consumed about 90% and 100% GAMG at 24 h and 12 h, respectively, regardless of culture conditions, and the consumption of GL was non-existent or negligible. Consumption of combined GL, GA and GAMG was similar to that of both combined GL and GA and combined GL and GAMG. It was found that intestinal flora can metabolize GL alone, but does not readily metabolize GL when present among its metabolites containing GL.