Evaluation of the first-pass glucuronidation of selected flavones in gut by Caco-2 monolayer model.
OBJECTIVE
Four flavones, namely Apigenin, Baicalein, Chrysin and Luteolin, were selected for study and comparison of their absorption and metabolism 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 significant 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-Basolateral transport studies were performed in Caco-2 models 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.
Ng
Siu Pong
SP
Faculty of Medicine, The Chinese University of Hong Kong, School of Pharmacy, Shatin, New Territories, Hong Kong.
Wong
Ka Yin
KY
Zhang
Li
L
Zuo
Zhong
Z
Lin
Ge
G
D001692:Biological Transport / Q000502:physiology; D018938:Caco-2 Cells; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods; D047309:Flavones / Q000737:chemistry / Q000378:metabolism*; D041981:Gastrointestinal Tract / Q000166:cytology / Q000378:metabolism*; D020719:Glucuronides / Q000378:metabolism*; D006801:Humans
D047309:Flavones; D020719:Glucuronides