Evaluation of the first-pass glucuronidation of selected flavones in gut by Caco-2 monolayer model.

PURPOSE. Four flavones, namely Apige- nin, Baicalein, Chrysin and Luteolin, were selected for study and comparison of their absorption and metabo- lism in gut using the in vitro Caco-2 monolayer model. METHODS. Transport of the four flavones in the Caco-2 monolayer model was studied in both Apical- to-Basolateral and Basolateral-to-Apical directions. RESULTS. All of the selected flavones were able to pass through the Caco-2 cell monolayer with no signif- icant efflux. The permeability coefficients of the four compounds were all greater than 10 -6 cm/sec and those of Apigenin and Baicalein were even greater than 10 -5 cm/sec. Glucuronides of the tested flavones were all formed in the Caco-2 cell monolayer model and a structure-activity relationship has been proposed for this glucuronidation. In addition, Apical-to-Basolat- eral transport studies were performed in Caco-2 mod- els pre-treated with Chrysin, an UGT inducer. Quantities of the corresponding glucuronides formed were all significantly higher in Chrysin-treated groups than the controls. CONCLUSIONS. It demonstrated that all selected flavones were substrates of the UGT isoforms that are inducible by Chrysin.