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

• Material Type: 博士論文
• Title: A novel orexin antagonist from a natural plant was discovered using zebrafish behavioural analysis
• Author/Editor: YAMANAKA, MIKIKO
• Author Heading: YAMANAKA, MIKIKO
• Publication, Distribution, etc.: 三重大学
• Publication Date: 2021-09-15
• Publication Date (W3CDTF): 2021-09-15
• Degree grantor/type: 三重大学
• Date Granted: 2021-09-15
• Date Granted (W3CDTF): 2021-09-15
• Dissertation Number: 甲医学第2082号
• Degree Type: 博士(医学)
• Conferring No. (Dissertation): 甲医学第2082号
• Text Language Code: eng
• Alias of Author: ヤマナカ, ミキコ; 山中, 実喜子
• Subject Heading: Zebrafish; Behaviour; Phenotype-based screening; Sleep; Orexin
• Target Audience: 一般
• Note (General): 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
• DOI: info:doi/10.26355/eurrev_202005_21207; https://doi.org/info:doi/10.26355/eurrev_202005_21207
• Persistent ID (NDL): info:ndljp/pid/11976680; https://dl.ndl.go.jp/pid/11976680
• Collection: 障害者向け資料
• Collection (Materials For Handicapped People:1): テキストデータ
• Collection (particular): 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• Acquisition Basis: 博士論文（自動収集）
• Date Accepted (W3CDTF): 2022-01-10T16:22:37+09:00
• Date Created (W3CDTF): 2022-01-04
• Format (IMT): application/pdf
• Access Restrictions: 国立国会図書館内限定公開
• Service for the Digitized Contents Transmission Service: 図書館・個人送信対象外
• Availability of remote photoduplication service: 可
• Periodical Title (URI): http://hdl.handle.net/10076/00020067; https://mie-u.repo.nii.ac.jp/records/14449
• Data Provider (Database): 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp