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Zebrafish-Based Phenotype Screening

                     

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.

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