title: Multiple ABC Transporters Efflux Baicalin.
abstract: Baicalein, the aglycone formed by hydrolysis of baicalin in the intestine, is well absorbed by passive diffusion but subjected to extensive intestinal glucuronidation. Efflux of baicalin, the low passive permeability glucuronide of baicalein from enterocytes, likely depends on a carrier-mediated transport. The present study was designed to explore potential drug-herb interaction by investigating the inhibitory effect of baicalin on the transport of reporter substrates by transporters and to identify the transporters responsible for the efflux of baicalin from enterocytes and hepatocytes. The interaction of baicalin with specific ABC transporters was studied using membranes from cells overexpressing human BCRP, MDR1, MRP2, MRP3 and MRP4. Baicalin was tested for its potential to inhibit vesicular transport by these transporters. The transport of baicalin by the selected transporters was also investigated. Transport by BCRP, MRP3 and MRP4 was inhibited by baicalin with an IC50 of 3.41 ± 1.83 μM, 14.01 ± 2.51 μM and 14.39 ± 5.69 μM respectively. Inhibition of MDR1 (IC50  = 94.84 ± 31.10 μM) and MRP2 (IC50  = 210.13 ± 110.49 μM) was less potent. MRP2 and BCRP are the apical transporters of baicalin that may mediate luminal efflux in enterocytes and biliary efflux in hepatocytes. The basolateral efflux of baicalin is likely mediated by MRP3 and MRP4 both in enterocytes and hepatocytes. Via inhibition of transport by ABC transporters, baicalin could interfere with the absorption and disposition of drugs.
authors.affiliation: Department of Pharmaceutics, Semmelweis University, Hőgyes E. utca 7., H-1092, Budapest, Hungary.
authors.forename: Bernadett
authors.identifier: http://orcid.org/0000-0002-3645-1220
authors.initials: B
authors.lastname: Kalapos-Kovács
authors.affiliation: Institute of Organic Chemistry, Research Centre for Natural Sciences, Hungarian Academy of Sciences (IOC RCNS HAS), Magyar Tudósok körútja 2., H-1117, Budapest, Hungary.
authors.forename: Balázs
authors.initials: B
authors.lastname: Magda
authors.affiliation: SOLVO Biotechnology, Gyár utca 2., H-2040, Budaörs, Hungary.
authors.forename: Márton
authors.initials: M
authors.lastname: Jani
authors.affiliation: SOLVO Biotechnology, Gyár utca 2., H-2040, Budaörs, Hungary.
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Fekete
authors.affiliation: Institute of Organic Chemistry, Research Centre for Natural Sciences, Hungarian Academy of Sciences (IOC RCNS HAS), Magyar Tudósok körútja 2., H-1117, Budapest, Hungary.
authors.forename: Pál T
authors.initials: PT
authors.lastname: Szabó
authors.affiliation: Department of Pharmaceutics, Semmelweis University, Hőgyes E. utca 7., H-1092, Budapest, Hungary.
authors.forename: István
authors.initials: I
authors.lastname: Antal
authors.affiliation: SOLVO Biotechnology, Gyár utca 2., H-2040, Budaörs, Hungary.
authors.forename: Péter
authors.initials: P
authors.lastname: Krajcsi
authors.affiliation: Department of Pharmaceutics, Semmelweis University, Hőgyes E. utca 7., H-1092, Budapest, Hungary.
authors.forename: Imre
authors.initials: I
authors.lastname: Klebovich
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects; D020895:Enterocytes / Q000187:drug effects* / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology*; D020719:Glucuronides / Q000494:pharmacology; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D041743:Herb-Drug Interactions; D006801:Humans
chemical_list: D018528:ATP-Binding Cassette Transporters; D005419:Flavonoids; D020719:Glucuronides; C038044:baicalin
keywords: ABC transporters; BCRP; MDR1; MRP; baicalin