title: Metabolic fate of fraxin administered orally to rats.
abstract: Naturally occurring fraxin (1) was administered orally to rats to investigate its metabolism. Urinary metabolites were analyzed by three-dimensional HPLC, and fraxetin-7-O-sulfate (2), fraxetin-7-O-beta-glucuronide (3), fraxetin (4), 6,7,8-trihydroxycoumarin (5), and fraxidin (6) were isolated. Fraxin (1) was extensively metabolized to 4, which was partly metabolized to 5 in a rat fecal suspension after incubation for 24 h. Urinary excretion of 4 and 5 in rats administered orally with 1 was substantially reduced when the rats were treated with antibiotics to suppress their intestinal flora. Incubation of 1 with a rat liver S-9 mixture yielded 6. These results suggest that hydrolysis and demethylation of 1 are performed by intestinal microflora, while methylation occurs in the liver.
authors.affiliation: Department of Phytochemistry, Tohoku Pharmaceutical University, Sendai, Miyagi 981-8558, Japan.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Yasuda
authors.forename: Mai
authors.initials: M
authors.lastname: Fukui
authors.forename: Takahiro
authors.initials: T
authors.lastname: Nakazawa
authors.forename: Ayumi
authors.initials: A
authors.lastname: Hoshikawa
authors.forename: Keisuke
authors.initials: K
authors.lastname: Ohsawa
mesh_terms: D000818:Animals; D003374:Coumarins / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology / Q000652:urine; D005243:Feces / Q000737:chemistry; D007422:Intestines / Q000187:drug effects / Q000382:microbiology*; D008099:Liver / Q000378:metabolism*; D008297:Male; D008745:Methylation; D015394:Molecular Structure; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D003374:Coumarins; C080614:fraxin