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The Functional Influences of Common ABCB1 Genetic Variants on the Inhibition of P-glycoprotein by Antrodia cinnamomea Extracts
Antrodia cinnamomea is a traditional healthy food that has been demonstrated to possess anti-inflammatory, antioxidative, and anticacer effects. The purpose of this study was to evaluate whether the ethanolic extract of A. cinnamomea (EEAC) can affect the efflux function of P-glycoprotein (P-gp) and...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3934917/ https://www.ncbi.nlm.nih.gov/pubmed/24586917 http://dx.doi.org/10.1371/journal.pone.0089622 |
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author | Sheu, Ming-Jyh Teng, Yu-Ning Chen, Ying-Yi Hung, Chin-Chuan |
author_facet | Sheu, Ming-Jyh Teng, Yu-Ning Chen, Ying-Yi Hung, Chin-Chuan |
author_sort | Sheu, Ming-Jyh |
collection | PubMed |
description | Antrodia cinnamomea is a traditional healthy food that has been demonstrated to possess anti-inflammatory, antioxidative, and anticacer effects. The purpose of this study was to evaluate whether the ethanolic extract of A. cinnamomea (EEAC) can affect the efflux function of P-glycoprotein (P-gp) and the effect of ABCB1 genetic variants on the interaction between EEAC and P-gp. To investigate the mechanism of this interaction, Flp-In™-293 cells stably transfected with various genotypes of human P-gp were established and the expression of P-gp was confirmed by Western blot. The results of the rhodamine 123 efflux assay demonstrated that EEAC efficiently inhibited wild-type P-gp function at an IC(50) concentration of 1.51±0.08 µg/mL through non-competitive inhibition. The IC(50) concentrations for variant-type 1236T-2677T-3435T P-gp and variant-type 1236T-2677A-3435T P-gp were 5.56±0.49 µg/mL and 3.33±0.67 µg/mL, respectively. In addition, the inhibition kinetics of EEAC also changed to uncompetitive inhibition in variant-type 1236T-2677A-3435T P-gp. The ATPase assay revealed that EEAC was an ATPase stimulator and was capable of reducing verapamil-induced ATPase levels. These results indicate that EEAC may be a potent P-gp inhibitor and higher dosages may be required in subjects carrying variant-types P-gp. Further studies are required to translate this basic knowledge into clinical applications. |
format | Online Article Text |
id | pubmed-3934917 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-39349172014-03-04 The Functional Influences of Common ABCB1 Genetic Variants on the Inhibition of P-glycoprotein by Antrodia cinnamomea Extracts Sheu, Ming-Jyh Teng, Yu-Ning Chen, Ying-Yi Hung, Chin-Chuan PLoS One Research Article Antrodia cinnamomea is a traditional healthy food that has been demonstrated to possess anti-inflammatory, antioxidative, and anticacer effects. The purpose of this study was to evaluate whether the ethanolic extract of A. cinnamomea (EEAC) can affect the efflux function of P-glycoprotein (P-gp) and the effect of ABCB1 genetic variants on the interaction between EEAC and P-gp. To investigate the mechanism of this interaction, Flp-In™-293 cells stably transfected with various genotypes of human P-gp were established and the expression of P-gp was confirmed by Western blot. The results of the rhodamine 123 efflux assay demonstrated that EEAC efficiently inhibited wild-type P-gp function at an IC(50) concentration of 1.51±0.08 µg/mL through non-competitive inhibition. The IC(50) concentrations for variant-type 1236T-2677T-3435T P-gp and variant-type 1236T-2677A-3435T P-gp were 5.56±0.49 µg/mL and 3.33±0.67 µg/mL, respectively. In addition, the inhibition kinetics of EEAC also changed to uncompetitive inhibition in variant-type 1236T-2677A-3435T P-gp. The ATPase assay revealed that EEAC was an ATPase stimulator and was capable of reducing verapamil-induced ATPase levels. These results indicate that EEAC may be a potent P-gp inhibitor and higher dosages may be required in subjects carrying variant-types P-gp. Further studies are required to translate this basic knowledge into clinical applications. Public Library of Science 2014-02-25 /pmc/articles/PMC3934917/ /pubmed/24586917 http://dx.doi.org/10.1371/journal.pone.0089622 Text en © 2014 Sheu et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Sheu, Ming-Jyh Teng, Yu-Ning Chen, Ying-Yi Hung, Chin-Chuan The Functional Influences of Common ABCB1 Genetic Variants on the Inhibition of P-glycoprotein by Antrodia cinnamomea Extracts |
title | The Functional Influences of Common ABCB1 Genetic Variants on the Inhibition of P-glycoprotein by Antrodia cinnamomea Extracts |
title_full | The Functional Influences of Common ABCB1 Genetic Variants on the Inhibition of P-glycoprotein by Antrodia cinnamomea Extracts |
title_fullStr | The Functional Influences of Common ABCB1 Genetic Variants on the Inhibition of P-glycoprotein by Antrodia cinnamomea Extracts |
title_full_unstemmed | The Functional Influences of Common ABCB1 Genetic Variants on the Inhibition of P-glycoprotein by Antrodia cinnamomea Extracts |
title_short | The Functional Influences of Common ABCB1 Genetic Variants on the Inhibition of P-glycoprotein by Antrodia cinnamomea Extracts |
title_sort | functional influences of common abcb1 genetic variants on the inhibition of p-glycoprotein by antrodia cinnamomea extracts |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3934917/ https://www.ncbi.nlm.nih.gov/pubmed/24586917 http://dx.doi.org/10.1371/journal.pone.0089622 |
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