The absorption and transport of six coumarins were passive diffusion as the dominating process.
METHODS AND RESULTS:
The P(app) values of umbelliferone, osthole, columbianadin, columbianetin acetate, angelol A and Angelol B from AP to BL side were (2.679+/-0.263) x 10(-5), (1.306+/-0.324) x 10(-5), (0.595+/-0.086) x 10(-6), (2.930+/-0.410) x 10(-6), (1.532+/-0.444) x 10(-5) and (1.413+/-0.243) x 10(-5) cm/s, and from BL to AP side were (3.381+/-0.410) x 10(-5), (0.898+/-0.134) x 10(-5), (0.510+/-0.183) x 10(-6), (0.222+/-0.025) x 10(-6), (1.203+/-0.280) x 10(-5) and (0.754+/-0.092) x 10(-5) cm/s, respectively. In this assay, the P(app) value of propranolol was 2.18 x 10(-5) cm/s and the P(app) value of atenolol was 2.77 x 10(-7) cm/s. Among the 6 coumarins, the P(app) values of umbelliferone, osthole, angelol A and Angelol B from AP to BL side were identical with that of propranolol, and columbianadin and columbianetin acetate lied between propranolol and atenolol. When replaced the HBSS with EBSS, and iodoacetamide or MK-591 were used in the experiment, the P(app) of Angelol B had no statistical difference as compared with the control group. In the mean total recoveries, umbelliferone was (83.31+/-3.52)%, angelol A was (77.39+/-7.38)%, osthole, columbianadin and Angelol B were between 50% to 65%, and columbianetin acetate was lower than 10%. The accumulation rates of osthole and columbianadin in the Caco-2 cells were (36.15+/-5.87)% and (53.90+/-4.39)%, respectively.
CONCLUSIONS:
The absorption and transport of umbelliferone, osthole, columbianadin, columbianetin acetate, angelol A and Angelol B are passive diffusion as the dominating process in Caco-2 cell monolayer model. Umbelliferone, osthole, angelol A and Angelol B are estimated to be highly absorbed compounds, and columbianadin and columbianetin acetate are estimated to be moderately absorbed compounds. In the Caco-2 cells, osthol and columbianadin appear to accumulate, and columbianetin acetate may be metabolized.
The absorption and transport of Angelol B are not influenced by the change of pH and the presence of iodoacetamide or MK571. |
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