title: Triterpenoid Saponins from the Caryophyllaceae Family Modulate the Efflux Activity of the P-Glycoprotein in an In Vitro Model of Intestinal Barrier.
abstract: The oralbioavailabilityof drugs is often limited due to the presence of the P-glycoprotein, an efflux pump strongly expressed on the luminal side of the intestinal barrier. In an attempt to circumvent drug efflux, strategies consisting in the coadministration of drugs with surface-active agents have been found to be promising. In this context, the role of saponins on the intestinal permeability of a P-glycoprotein substrate was investigated. The P-glycoprotein inhibition activity of three triterpenoid saponins extracted from several plants of the Caryophyllaceae family was evaluated using an intestinal barrier model comprised of Caco-2 cell lines. The results showed a strong effect of two saponins on P-glycoprotein-mediated transport. At a concentration of 15 µM, the efflux ratio was close to 1 for both saponins, thus suggesting a total inhibition of the efflux pump in contrast to verapamil HCl, a conventional P-glycoprotein inhibitor. In addition, measurements of the transepithelial electrical resistance revealed that the integrity of the monolayers was not altered at such concentrations, thereby reducing potential adverse effects. The presence of acetylated sugars in the saponin structure could possibly facilitate interactions with the efflux pump by an ATP-dependent mechanism or by fluidization of cell membranes.
authors.affiliation: FDE EA4267, Université Bourgogne Franche-Comté, UFR des Sciences Médicales et Pharmaceutiques, Laboratoire de Pharmacie galénique, Besançon cedex, France.
authors.forename: Océane
authors.initials: O
authors.lastname: Dubray
authors.affiliation: FDE EA4267, Université Bourgogne Franche-Comté, UFR des Sciences Médicales et Pharmaceutiques, Laboratoire de Pharmacie galénique, Besançon cedex, France.
authors.forename: Brice
authors.initials: B
authors.lastname: Moulari
authors.affiliation: FDE EA4267, Université Bourgogne Franche-Comté, UFR des Sciences Médicales et Pharmaceutiques, Laboratoire de Pharmacie galénique, Besançon cedex, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Chrétien
authors.affiliation: FDE EA4267, Université Bourgogne Franche-Comté, UFR des Sciences Médicales et Pharmaceutiques, Laboratoire de Pharmacie galénique, Besançon cedex, France.
authors.forename: Yann
authors.initials: Y
authors.lastname: Pellequer
authors.affiliation: FDE EA4267, Université Bourgogne Franche-Comté, UFR des Sciences Médicales et Pharmaceutiques, Laboratoire de Pharmacie galénique, Besançon cedex, France.
authors.forename: Alf
authors.initials: A
authors.lastname: Lamprecht
authors.affiliation: FDE EA4267, Université Bourgogne Franche-Comté, UFR des Sciences de Santé, Laboratoire de Pharmacognosie, Dijon cedex, France.
authors.forename: Anne-Claire
authors.initials: AC
authors.lastname: Mitaine-Offer
authors.affiliation: FDE EA4267, Université Bourgogne Franche-Comté, UFR des Sciences de Santé, Laboratoire de Pharmacognosie, Dijon cedex, France.
authors.forename: Marie-Aleth
authors.initials: MA
authors.lastname: Lacaille-Dubois
authors.affiliation: FDE EA4267, Université Bourgogne Franche-Comté, UFR des Sciences Médicales et Pharmaceutiques, Laboratoire de Pharmacie galénique, Besançon cedex, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Béduneau
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018938:Caco-2 Cells; D029748:Caryophyllaceae / Q000737:chemistry*; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D010539:Permeability / Q000187:drug effects; D012503:Saponins / Q000302:isolation & purification / Q000494:pharmacology*; D014315:Triterpenes / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D012503:Saponins; D014315:Triterpenes