Journal of Natural Products 2006-05-01

Metabolic fate of fraxin administered orally to rats.

Takaaki Yasuda, Mai Fukui, Takahiro Nakazawa, Ayumi Hoshikawa, Keisuke Ohsawa

Index: J. Nat. Prod. 69(5) , 755-7, (2006)

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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.