title: Permeability characteristics and membrane affinity of flavonoids and alkyl gallates in Caco-2 cells and in phospholipid vesicles.
abstract: Biomembrane interactions of flavonoids and alkyl gallates were investigated using transport studies on Caco-2 cells and membrane affinity experiments in phospholipid vesicles. Flavone was rapidly absorbed across the cell monolayer (P(app),380 x 10(-6) cm/s), whereas efficient uptake but no apical to basolateral transport was observed with the flavonoids with higher degree of hydroxylation (e.g., quercetin and luteolin). The transport of alkyl gallates was governed by the length of the alkyl chain, i.e., methyl and propyl gallate were absorbed while octyl gallate showed cellular uptake but no transport. Flavonoids with several hydroxyl groups exhibited highest affinity for vesicle membranes, partition coefficients being 7.1 and 7.5 microM for luteolin and quercetin, respectively. In conclusion, the degree of hydroxylation, molecular configuration, and length of the side chain of flavonoids and alkyl gallates seem to have a highly important impact on their membrane affinity as well as on their permeability characteristics in Caco-2 cells.
authors.affiliation: Viikki Drug Discovery Technology Center, Faculty of Pharmacy, University of Helsinki, P.O. Box 56, FIN-00014, Helsinki, Finland.
authors.forename: Päivi
authors.initials: P
authors.lastname: Tammela
authors.forename: Leena
authors.initials: L
authors.lastname: Laitinen
authors.forename: Anna
authors.initials: A
authors.lastname: Galkin
authors.forename: Tero
authors.initials: T
authors.lastname: Wennberg
authors.forename: Robert
authors.initials: R
authors.lastname: Heczko
authors.forename: Heikki
authors.initials: H
authors.lastname: Vuorela
authors.forename: J Peter
authors.initials: JP
authors.lastname: Slotte
authors.forename: Pia
authors.initials: P
authors.lastname: Vuorela
mesh_terms: D000042:Absorption; D000327:Adsorption; D018938:Caco-2 Cells; D002462:Cell Membrane / Q000378:metabolism*; D002463:Cell Membrane Permeability / Q000502:physiology*; D005419:Flavonoids / Q000737:chemistry* / Q000493:pharmacokinetics*; D005707:Gallic Acid / Q000031:analogs & derivatives / Q000737:chemistry* / Q000493:pharmacokinetics*; D006801:Humans; D008081:Liposomes / Q000737:chemistry*; D010539:Permeability; D010743:Phospholipids / Q000737:chemistry*
chemical_list: D005419:Flavonoids; D008081:Liposomes; D010743:Phospholipids; D005707:Gallic Acid