論文

査読有り
2020年

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

European Review for Medical and Pharmacological Sciences
  • M. Yamanaka
  • ,
  • H. Iwata
  • ,
  • K. Masuda
  • ,
  • M. Araki
  • ,
  • Y. Okuno
  • ,
  • M. Okamura
  • ,
  • J. Koiwa
  • ,
  • T. Tanaka

24
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
DOI
https://doi.org/10.26355/eurrev_202005_21207
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/32432777
Scopus
https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85085157311&origin=inward
Scopus Citedby
https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=85085157311&origin=inward
ID情報
  • DOI : 10.26355/eurrev_202005_21207
  • ISSN : 1128-3602
  • eISSN : 2284-0729
  • PubMed ID : 32432777
  • SCOPUS ID : 85085157311

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