Glucuronidation is the dominating in vivo metabolism pathway of herbacetin: Elucidation of herbacetin pharmacokinetics after intravenous and oral administration in rats

Abstract

The promising potential benefits of herbacetin in human entail its pharmacokinetic investigations, but the metabolic fate of this natural compound in vivo remains a field of unknown so far. The current study, for the first time, identified and quantified seven herbacetin-metabolites from rat urine, feces and bile after administration of herbacetin to rats. It was found that herbacetin was excreted primarily from rat urine in the form of glucuronide-conjugations. Subsequent in vitro enzyme kinetic studies and in vivo pharmacokinetic investigations suggested an extensive hepatic metabolism of herbacetin and the high exposure of herbacetin-glucuronides in systemic circulation. The clearance, t1/2 and bioavailability of herbacetin in rats were determined as 16.4 ± 1.92 ml·kg/min, 11.9 ± 2.7 min, and 1.32%, respectively. On basis of these findings, a comprehensive metabolic pathway of herbacetin in rats was composed, which was crucial for the further assessments of herbacetin therapeutic effects and mechanism of pharmacological action.

Keywords

• Herbacetin
• Pharmacokinetics
• Biotransformation
• Glucuronidation
• Hepatic metabolism
• Colonic degradation