Abstract: Piceatannol-4′-O-β-D-glucopyranoside (PG),a natural antioxidant abundant in Rheum emodi Wall,was found to be an easihy metabolized substrate.The present study was aimed to study glucuronidation of PG in rat in vivo and in vitro. Rat bile samples were collected after a single intravenous bolus injection of PG at dose of 20 mg/kg.The metabolic profiling was performed using LC-MS,and the principal glucuronide metabolites were deduced.Then in vitro glucuronidation was investigated in rat liver microsomes,and the kinetic properties were determined.The results showed that PG can be quickly metabolized to glucuronide metabolites after intravenous administration in rat.In the in vitro co-incubation system containing PG and rat liver microsomes,two main mono-glucuronide metabolites of PG were observed,and the metabolic profile was found to be similar to that in vivo. The maximum reaction rate (V_max) of glucuronidation was 10-11 nmol/(min·mg), Michaelis-Menten constant (K_m) was 0.36 mmol/L,and liver clearance (CL_int) was 0.028 mL/(min·mg),respectively.All the findings indicated that UGTs in rat liver have fairly high affinity with PG and were responsible for the rapid glucuronidation of PG,which was one of the main elimination pathways of PG in rat.

Key words: piceatannol-4&prime, -O-&beta, -D-glucopyranoside, glucuronidation, rat bile, liver microsomes, metabolic kinetics