Intestinal bacterial hydrolysis is indispensable to absorption of 18 beta-glycyrrhetic acid after oral administration of glycyrrhizin in rats.
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.
Akao
T
T
Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Japan.
Hayashi
T
T
Kobashi
K
K
Kanaoka
M
M
Kato
H
H
Kobayashi
M
M
Takeda
S
S
Oyama
T
T
D000284:Administration, Oral; D000818:Animals; D002432:Cecum / Q000378:metabolism* / Q000382:microbiology*; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D005051:Eubacterium / Q000502:physiology; D005243:Feces / Q000382:microbiology; D006034:Glycyrrhetinic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism*; D019695:Glycyrrhizic Acid; D006801:Humans; D006868:Hydrolysis; D007124:Immunoenzyme Techniques; D007408:Intestinal Absorption / Q000502:physiology*; D008297:Male; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D017208:Rats, Wistar; D013291:Streptococcus / Q000502:physiology
D019695:Glycyrrhizic Acid; D006034:Glycyrrhetinic Acid