Interaction of Phytocompounds of Echinacea purpurea with ABCB1 and ABCG2 Efflux Transporters
| Autor: | Henrike Bruckmueller, Ingolf Cascorbi, Charles Awortwe, Meike Kaehler |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Cichoric acid
Pharmaceutical Science 02 engineering and technology Pharmacology 021001 nanoscience & nanotechnology 030226 pharmacology & pharmacy 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine chemistry Phytochemical Cell culture Drug Discovery Echinacoside Caffeic acid Molecular Medicine Cytotoxic T cell Viability assay 0210 nano-technology Intracellular |
| Zdroj: | Molecular Pharmaceutics. 18:1622-1633 |
| ISSN: | 1543-8392 1543-8384 |
| DOI: | 10.1021/acs.molpharmaceut.0c01075 |
| Popis: | This 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 https://doi.org/10.1021/acs.molpharmaceut.0c01075, see ACS Articles on Request. Preparations 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, B |
| Databáze: | OpenAIRE |
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