title: Anthocyanidins but not anthocyanins inhibit P-glycoprotein-mediated calcein extrusion - possible implication for orally administered drugs.
abstract: P-glycoprotein (P-gp) inhibition represents a promising therapeutic strategy for oncologic patients. The inhibition by naturally occurring anthocyans would bring certain benefits. Unfortunately, due to the low bioavailability and consequently low blood level, they cannot be used for cancer therapy. However, due to the food supplementation, significant concentration can raise up in the intestine, where P-gp is abundantly expressed. As many drugs are orally taken, simultaneous administration might affect the concentration of these drugs in the blood. Here, we found that anthocyanidins (aglycons) but not anthocyanins (glycosides) can significantly inhibit P-gp up to 60% of positive control, verapamil. This inhibitory activity was observed for 500 μm concentrations of malvidin and pelargonidin. We conclude that these compounds may be the source of food-drug interactions either for orally taken drugs or for intravenously administered drugs eliminated via biliary excretion which are the substrates of P-gp.
authors.affiliation: Department of Cell Biology and Genetics, Faculty of Science, Palacky University, Slechtitelu 27, 783 71, Olomouc, Czech Republic.
authors.forename: Radim
authors.initials: R
authors.lastname: Vrzal
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D000872:Anthocyanins / Q000008:administration & dosage* / Q000378:metabolism; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D005452:Fluoresceins / Q000008:administration & dosage* / Q000378:metabolism; D018565:Food-Drug Interactions / Q000502:physiology; D006801:Humans; D013552:Swine; D014700:Verapamil / Q000008:administration & dosage / Q000378:metabolism
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000872:Anthocyanins; D005452:Fluoresceins; D014700:Verapamil; C007740:fluorexon
keywords: MDR1; calcein assay; inhibition; malvidin; pelargonidin