Metabolic fate of orally administered phyllodulcin in rats.

Naturally occurring phyllodulcin (1) was orally administered to rats to investigate its metabolic fate. Urinary metabolites were analyzed by three-dimensional HPLC. Phyllodulcin-3'-O-sulfate (2), phyllodulcin-3'-O-beta-glucuronide (3), 2-[2-(3,4-dihydroxyphenyl)ethyl]-6-hydroxybenzoic acid (4), and one novel bibenzyl derivative, 2-[2-(3-hydroxy-4-methoxyphenyl)ethyl]-6-hydroxybenzoic acid (5), together with thunberginol G (6) and hydrangenol (7) were isolated from the phyllodulcin-treated urine. 1 was extensively metabolized to 4-6 by a rat fecal suspension after incubation for 24 h. Urinary excretion of 4-6 in rats administered phyllodulcin orally was substantially reduced when the rats were treated with antibiotics to suppress their intestinal flora. On the other hand, the incubation of 1 with rat liver S-9 mix showed the presence of 7 together with 4 and 5.