Intestinal bacterial hydrolysis is indispensable to absorption of 18 beta-glycyrrhetic acid after oral administration of glycyrrhizin in rats

Abstract

Gnotobiote rats were prepared by infecting germ-free rats with Eubacterium sp. strain GLH, a human intestinal bacterium capable of hydrolysing glycyrrhizin to 18 beta-glycyrrhetic acid. Their faeces and caecal contents showed glycyrrhizin-hydrolysing activities (31.7 and 31.3 pmol min-1 (mg protein)-1, respectively) similar to those (81.0 and 39.9 pmol min-1 (mg protein)-1, respectively) of conventional rats, although there was no detectable activity in germ-free rats. When glycyrrhizin (100 mg kg-1) was orally administered to conventional, germ-free and gnotobiote rats, no glycyrrhizin could be detected in plasma 4 or 17 h after the administration, using EIA and HPLC assays. Plasma 18 beta-glycyrrhetic acid was not detected 4 or 17 h after the administration of glycyrrhizin to germ-free rats nor could this compound be detected in caecal contents or in the faeces. However, 18 beta-glycyrrhetic acid (0.6-2.6 nmol mL-1) was detected in plasma of the conventional and the gnotobiote rats 4 and 17 h after the administration, and the caecal contents after 4 h and the cumulative faeces up to 17 h of the conventional and the gnotobiote rats contained considerable amounts of 18 beta-glycyrrhetic acid. These findings indicate that orally administered glycyrrhizin is poorly absorbed from the gut, but is hydrolysed to 18 beta-glycyrrhetic acid by intestinal bacteria such as E. sp. strain GLH, and the resulting 18 beta-glycyrrhetic acid is absorbed.