ZEBRAFISH

新しいハイスループット個別ゼブラフィッシュ腎毒性スクリーニングシステムの創生と応用

次世代がんの個別化医療とゼブラフィッシュ飼育品質管理システム

ゼブラフィッシュ創薬の利点と課題

新しい心毒性防御遺伝子stannniocalcin1の臨床応用

PDXZ and Tour Angiogenesis Analysis

Aging-associated microstructural deterioration of vertebra in zebra fi sh

患者がん移植ゼブラフィッシュモデル(PDXZ)と抗体医薬

zebrafish認知症モデルスクリーニングによる新規治療薬開発の成功例

ゼブラフィッシュ創薬の課題と克服戦略

zebrafish dementia models

一覧へ

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

2020/05/25

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.