Baicalein is a dietary flavonoid that exhibits a variety of intestinal pharmacological activities with limited oral bioavailability. In the present study, the intestinal pharmacokinetics of baicalein was determined by HPLC-ESI-MS/MS and HPLC-PDA analysis. After oral administration, the intestinal concentration of baicalein was peaked at 1 h, and the amount of baicalein in the intestine corresponded to 87%, 45%, and 20% of the administered dose at 1 h, 8 h, and 12 h, respectively. Glucuronidation, sulfation, and methylation metabolites were the major metabolites of baicalein in the small intestine, including duodenum, jejunum, and ileum. Dehydroxylation, sulfation, and methylation metabolites were the major metabolites in the large intestine, including cecum and colon. In vitro, baicalein was transformed into its glucuronidation and methylation metabolites in hepatic and intestinal S9 fraction. The glucuronidation metabolites was hydrolyzed to baicalein by gut microbiota, but the dehydroxylation and methylation metabolites were stable during gut microbiota incubation.

In conclusion, the intestinal concentration of baicalein can support its intestinal pharmacological activities, and the present study may provide useful information for understanding the bioactivities of flavonoids with limited systemic bioavailability.