The Metabolism of Umbelliferone and Herniarin in Rats and by the Rat Intestinal Microflora

Abstract

1. The metabolism of umbelliferone (7-hydroxycoumarin) and herniarin (7-methoxycoumarin) was studied in rats after oral and intraperitoneal administration.

2. Umbelliferone was excreted in the urine partly unchanged but mainly as a glucuronide and/or sulphate conjugate. It was also metabolized to 2,4-dihydroxyphenylpropionic acid and, following intraperitoneal dosage, to a very small amount of 3,7-dihydroxycoumarin.

3. Herniarin was metabolized to the following unconjugated urinary metabolites: 2-hydroxy-4-methoxyphenylacetic acid (major metabolite), 2-hydroxy-4-methoxyphenylpropionic acid, 2,4-dihydroxyphenylpropionic acid, 2-hydroxy-4-methoxyphenyllactic acid and umbelliferone (trace). A trace of unchanged compound was excreted. The conjugated metabolites excreted were umbelliferone, 3,7-dihydroxycoumarin, 3-hydroxy-7-methoxycoumarin, isoscopoletin and two unidentified metabolites.

4. The metabolism of umbelliferone and herniarin and a few related compounds by the rat caecal microflora was investigated. Umbelliferone was metabolized to 2,4-dihydroxyphenylpropionic acid, presumably by way of 3,4-dihydro-7-hydroxycoumarin. Herniarin was metabolized to 2-hydroxy-4-methoxyphenylpropionic acid and 2,4-dihydroxyphenylpropionic acid.

5. The excretion of the phenylpropionic acid derivatives was reduced or abolished when neomycin-treated rats were used. These metabolites were absent from the urines of germ-free rats following the administration of umbelliferone and herniarin. These results, together with those from the caccal incubates, indicate that the phenylpropionic acid derivatives are formed from the coumarms by the gastrointestinal microflora.