2020年
A novel orexin antagonist from a natural plant was discovered using zebrafish behavioural analysis
European Review for Medical and Pharmacological Sciences
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- 巻
- 24
- 号
- 9
- 開始ページ
- 5127
- 終了ページ
- 5139
- 記述言語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.26355/eurrev_202005_21207
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.
- リンク情報
- ID情報
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- DOI : 10.26355/eurrev_202005_21207
- ISSN : 1128-3602
- eISSN : 2284-0729
- PubMed ID : 32432777
- SCOPUS ID : 85085157311