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Publication List English
2024/08/06
2024/05/21
2021/10/31
Generation of a Transgenic Zebrafish Line for In Vivo Assessment of Hepatic Apoptosis
2021/08/19
2021/07/09
Establishment of a Quality Control Protocol for Zebrafish Developmental Toxicity Studies
2020/10/13
2020/05/28
A novel orexin antagonist from a natural plant was discovered using zebrafish behavioural analysis
2019/10/15
C3orf70 Is Involved in Neural and Neurobehavioral Development
2019/09/22
2019/07/17
Aging-associated microstructural deterioration of vertebra in zebrafish
A novel orexin antagonist from a natural plant was discovered using zebrafish behavioural analysis
2020/05/28
Eur Rev Med Pharmacol Sci. 2020 May;24(9):5127-5139.
doi: 10.26355/eurrev_202005_21207.
M Yamanaka, H Iwata, K Masuda, M Araki, Y Okuno, M Okamura, J Koiwa, T Tanaka
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-ΘB (NF-ΘB) 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.
