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dc.contributor.authorAwortwe, Charles
dc.contributor.authorBruckmüller, Henrike
dc.contributor.authorKaehler, Meike
dc.contributor.authorCascorbi, Ingolf
dc.date.accessioned2022-04-08T11:54:13Z
dc.date.available2022-04-08T11:54:13Z
dc.date.issued2021-03-17
dc.description.abstractPreparations of Echinacea purpurea (E. purpurea) are widely used for the management of upper respiratory infections, influenza, and common cold, often in combination with other conventional drugs. However, the potential of phytochemical constituents of E. purpurea to cause herb−drug interactions via ABCB1 and ABCG2 efflux transporters remains elusive. The purpose of this study was to investigate the impact of E. purpurea-derived caffeic acid derivatives (cichoric acid and echinacoside) and tetraenes on the mRNA and protein expression levels as well as on transport activity of ABCB1 and ABCG2 in intestinal (Caco-2) and liver (HepG2) cell line models. The safety of these compounds was investigated by estimating EC20 values of cell viability assays in both cell lines. Regulation of ABCB1 and ABCG2 protein in these cell lines were analyzed after 24 h exposure to the compounds at 1, 10, and 50 μg/mL. Bidirectional transport of 0.5 μg/mL Hoechst 33342 and 5 μM rhodamine across Caco-2 monolayer and profiling for intracellular concentrations of the fluorophores in both cell lines were conducted to ascertain inhibition effects of the compounds. Cichoric acid showed no cytotoxic effect, while the EC20 values of tetraenes and echinacoside were 45.0 ± 3.0 and 52.0 ± 4.0 μg/mL in Caco-2 cells and 28.0 ± 4.3 and 62.0 ± 9.9 μg/mL in HepG2 cells, respectively. In general, the compounds showed heterogeneous induction of ABCB1 with the strongest 3.6 ± 1.2-fold increase observed for 10 μg/mL tetraenes in Caco-2 cells (p < 0.001). However, the compounds did not induce ABCG2. None of the phytocompounds inhibited significantly net flux of the fluorophores across Caco-2 monolayers. Overall, tetraenes moderately induced ABCB1 but not ABCG2 in Caco-2 and HepG2 cells while no compound significantly inhibited activity of these transporters at clinically relevant concentration to cause herb−drug interactions. KEYWORDS: Echinacea purpurea, caffeic acid derivatives, tetraenes, P-gp, Ben_US
dc.descriptionThis document is the Accepted Manuscript version of a Published Work that appeared in final form in Molecular Pharmaceutics, copyright © 2021 American Chemical Societ, after peer review and technical editing by the publisher. To access the final edited and published work see <a href=https://doi.org/10.1021/acs.molpharmaceut.0c01075>https://doi.org/10.1021/acs.molpharmaceut.0c01075</a>, see ACS Articles on Request.en_US
dc.identifier.citationAwortwe, Bruckmüller H, Kaehler, Cascorbi. Interaction of Phytocompounds of Echinacea purpurea with ABCB1 and ABCG2 Efflux Transporters. Molecular Pharmaceutics. 2021;18(4):1622-1633en_US
dc.identifier.cristinIDFRIDAID 1993969
dc.identifier.doi10.1021/acs.molpharmaceut.0c01075
dc.identifier.issn1543-8384
dc.identifier.issn1543-8392
dc.identifier.urihttps://hdl.handle.net/10037/24739
dc.language.isoengen_US
dc.publisherAmerican Chemical Societyen_US
dc.relation.journalMolecular Pharmaceutics
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2021 The Author(s)en_US
dc.titleInteraction of Phytocompounds of Echinacea purpurea with ABCB1 and ABCG2 Efflux Transportersen_US
dc.type.versionacceptedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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