@phdthesis{oai:mie-u.repo.nii.ac.jp:00014449,
 author = {YAMANAKA, MIKIKO and 山中, 実喜子},
 month = {Sep},
 note = {application/pdf, 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, 8β-(4'-Hydroxytigloyloxy) costunolide (8β), 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 8β 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., 本文/Department of Systems Pharmacology, Mie University, Graduate School of Medicine, Tsu, Mie, Japan, 13p},
 school = {三重大学},
 title = {A novel orexin antagonist from a natural plant was discovered using zebrafish behavioural analysis},
 year = {2021},
 yomi = {ヤマナカ, ミキコ}
}