論文 - 詳細
| RRC ID | 30487 |
|---|---|
| 著者 | Sheu MJ, Teng YN, Chen YY, Hung CC. |
| タイトル | The functional influences of common ABCB1 genetic variants on the inhibition of P-glycoprotein by Antrodia cinnamomea extracts. |
| ジャーナル | PLoS One |
| Abstract |
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 IC50 concentration of 1.51 ± 0.08 µg/mL through non-competitive inhibition. The IC50 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. |
| 巻・号 | 9(2) |
| ページ | e89622 |
| 公開日 | 2014-1-1 |
| DOI | 10.1371/journal.pone.0089622 |
| PII | PONE-D-13-43939 |
| PMID | 24586917 |
| PMC | PMC3934917 |
| MeSH | ATP Binding Cassette Transporter, Subfamily B / antagonists & inhibitors ATP Binding Cassette Transporter, Subfamily B / genetics ATP Binding Cassette Transporter, Subfamily B, Member 1 / antagonists & inhibitors* ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics* ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism Adenosine Triphosphatases / metabolism Antrodia / chemistry* Genetic Variation HEK293 Cells Humans Plant Extracts / pharmacology* RNA, Messenger / genetics RNA, Messenger / metabolism Rhodamine 123 / metabolism |
| IF | 2.74 |
| 引用数 | 11 |
| WOS 分野 | PHARMACOLOGY & PHARMACY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 5 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 遺伝子材料 | Human MDR1 cDNA (RDB01372) |