最近の記事
- 2024/10/01
- 大学院生募集中 2024年10月16日(水)ー18日(金)
- 2024/07/01
- 患者がん移植ゼブラフィシュモデルの個別化医療戦略
- 2024/06/06
- AI(人工知能)ゼブラフィッシュ創薬の新しい展開
- 2024/05/29
- システムズ薬理学大学院入試説明会
- 2024/04/17
- ２０２４（令和６）年度 大学院生募集中
- 2023/03/02
- 研究員募集中
- 2020/06/08
- 大学院生のゼブラフィッシュ創薬論文が出版されました。
| 2020/06/08 |
|
大学院生のゼブラフィッシュ創薬論文が出版されました。
A novel orexin antagonist from a natural plant was discovered using zebrafish behavioural analysis
M. YAMANAKA1, H. IWATA2, K. MASUDA2, M. ARAKI2, Y. OKUNO2,
M. OKAMURA1, J. KOIWA1, T. TANAKA1
1Department of Systems Pharmacology, Mie University, Graduate School of Medicine, Tsu, Mie, Japan
2Graduate School of Medicine, Kyoto University, Kyoto, Japan
Abstract. – OBJECTIVE: Phenotypic screening is one of the most practical approaches
to the identification of mediators of behaviour,
since it is difficult to model brain function in vitro, at a cellular level. We used a zebrafish (Danio rerio) behavioural assay to discover novel,
natural, neuroactive compounds.
MATERIALS AND METHODS: A zebrafish
behavioural assay was performed for seven
natural compounds, obtained from plants. The
behavioural profiles were compared to those of
known psychoactive drugs. We characterised a
natural compound exhibiting a behaviour profile
similar to that of suvorexant, using in silico, in
vitro and microarray expression analysis.
RESULTS: The behavioural analysis performed
in this study classified central nervous system
drugs according to their mechanism. Zebrafish
treated with a natural compound, 8b-(4'-Hydroxytigloyloxy) costunolide (8b), showed behaviour
profiles similar to those of zebrafish treated with
suvorexant, a known orexin antagonist. This behavioural assay was validated using in silico and
in vitro assays, which revealed that the new compound was a dual orexin receptor antagonist. In
addition, transcriptome analysis suggested that
8b might regulate the nuclear factor-κB (NF-κB)
related pathway.
CONCLUSIONS: We conclude that zebrafish
phenotypic screening, combined with in silico
assays and gene expression profiling, is a useful
strategy to discover and characterize novel therapeutic compounds, including natural products.
関連リンク
- 三重大学メディカルゼブラフィッシュ研究センター
- Department of Systems Pharmacology Mie University Graduate School of Medicine
関連ファイル
