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最近の記事

2025/05/01
In Vivo Assessment of Individual and Total Proteinuria in Zebrafish Larvae Using the Solvatochromic Compound ZMB741
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ゼブラフィッシュ創薬のグローバル展開
2024/10/28
医療ビッグデータ時代における次世代AIDXゼブラフィッシュ創薬研究開発
2024/09/02
ゼブラフィッシュによるOncocardiologyとOnconephrology
2024/07/01
Personalized cancer treatment using PDX zebrafish model
2024/06/20
The world's most powerful high-throughput individualized in vivo proteinuria screening system
2024/06/11
in vivo 血漿蛋白蛍光色素ZMB741による蛋白尿定量スクリーニング

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2020/05/25
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A novel orexin antagonist from a natural plant was discovered using zebrafish behavioural analysis

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

  • European Review for Medical and Pharmacological Sciences
  • Department of Systems Pharmacology Mie University Graduate School of Medicine

関連ファイル

  • A novel orexin antagonist from a natural plant was discovered using zebrafish behavioural analysis