morin and verlukast

In this study, we chose three of the flavonoids isorhamnetin-3-O-rutinoside(IRR) diosmetin-7-O-beta-D-xylopyranosyl-(1-6)-beta-D-glucopyranoside(DXG) and morin, which showed obvious efflux, to test the hypothesis that a specific efflux transporter is responsible for their transportation.. The intestinal epithelial membrane transport of the flavonoids were examined using the monolayer of the human Caco-2 cell line grown in Transwells, a common model of intestinal absorption. The flavonoids were measured by high performance liquid chromatography with UV detector.. The efflux of morin, IRR and DXG, across Caco-2 cell monolayers was examined over the concentration range from 2 to 200 microM and showed a saturable process. The depletion of the cellular ATP stores with 5 mM iodoacetamide led to a significant inhibition of the efflux. Fifty micromolar verapamil, a chemical inhibitor of P-glycoprotein, had no effect on the transport of the three flavonoids, while the presence of 50 microM MK-571 and 1 mM probenecid, MRP inhibitors, resulted in an obvious reduction in the efflux. Moreover, inhibition of morin transport by MK-571 demonstrated concentration dependence. The transportation of the three flavonoids was compared with apigenin.. These data support a role for MRPs in the intestinal transcellular efflux of morin, IRR, DXG and possibly other hydrophilic flavonoid aglycons and glycosides.

Topics: Adenosine Triphosphate; Antioxidants; Biological Transport, Active; Caco-2 Cells; Chromatography, High Pressure Liquid; Disaccharides; Enzyme Inhibitors; Flavonoids; Humans; Intestinal Mucosa; Iodoacetamide; Probenecid; Propionates; Quercetin; Quinolines; Verapamil

The influence of novel synthetic and plant origin flavonoids on activity of multidrug resistance-associated protein (MRP1) was investigated in human erythrocytes used as a cell model expressing MRP1 in plasma membrane. The fluorescent probe, BCPCF (2', 7'-bis-(3-carboxy-propyl)-5-(and-6)-carboxyfluorescein), was applied as a substrate for MRP1 multidrug resistance transporter. The effect of compounds belonging to different classes of natural flavonoids: flavone, flavonol, isoflavones and flavanolignan was compared with action of new synthetic derivatives of genistein. Most of the flavonoids showed strong or moderate ability to inhibit transport carried out by MRP1. Inhibitory properties of flavonoids were compared to the effects of indomethacin, probenecid and MK-571 known as MRP1 inhibitors. Studying the influence of new synthetic genistein derivatives on BCPCF transport we have found that the presence of hydrophobic groups substituting hydrogen of hydroxyl group at the position 4' in ring B of isoflavone is more important for inhibitory properties than hydrophobic substitution at the position 7 in ring A. In case of naturally occurring isoflavones the replacement of hydrogen at position 4' by hydrophobic ring structure seems also to be favourable for inhibition potency.

Topics: Dose-Response Relationship, Drug; Erythrocytes; Flavonoids; Fluoresceins; Genistein; Hemolysis; Humans; Indomethacin; Multidrug Resistance-Associated Proteins; Plants; Propionates; Protein Transport; Quinolines; Silybin; Silymarin