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

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Abstract
Gnotobiote rats were prepared by infecting germ-free rats with Eubaclerium sp. strain GLH, a human intestinal bacterium capable of hydrolysing glycyrrhizin to 18β-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 18β-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, 18β-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 18β-glycyrrhetic acid. These findings indicate that orally administered glycyrrhizin is poorly absorbed from the gut, but is hydrolysed to 18β-glycyrrhetic acid by intestinal bacteria such as E. sp. strain GLH, and the resulting 18β-glycyrrhetic acid is absorbed.
Funding Information
  • Takeda Science Foundation