Preliminary safety assessment of oridonin in zebrafish

Bibliographic Details
Title: Preliminary safety assessment of oridonin in zebrafish
Authors: Lili Tian, Donglai Sheng, Qiushuang Li, Chenxu Guo, Guofu Zhu
Source: Pharmaceutical Biology, Vol 57, Iss 1, Pp 632-640 (2019)
Publisher Information: Taylor & Francis Group, 2019.
Publication Year: 2019
Collection: LCC:Therapeutics. Pharmacology
Subject Terms: isodon rubescens, medicinal plant, embryonic development effects, body length, swimming speed, vegfr3, Therapeutics. Pharmacology, RM1-950
More Details: Context: Oridonin, isolated from the leaves of Isodon rubescens (Hemsl.) H.Hara (Lamiaceae), has good antitumor activity. However, its safety in vivo is still unclear. Objective: To investigate the preliminary safety of oridonin in zebrafish. Materials and methods: Embryo, larvae and adult zebrafish (n = 40) were used. Low, medium and high oridonin concentrations (100, 200 and 400 mg/L for embryo; 150, 300 and 600 mg/L for larvae; 200, 400 and 800 mg/L for adult zebrafish) and blank samples were administered. At specific stages of zebrafish development, spontaneous movement, heartbeat, hatching rate, etc., were recorded to assess the developmental effects of oridonin. VEGFA, VEGFR2 and VEGFR3 gene expression were also examined. Results: Low-dose oridonin increased spontaneous movement and hatching rate with median effective doses (ED50) of 115.17 mg/L at 24 h post-fertilization (hpf) and 188.59 mg/L at 54 hpf, but these values decreased at high doses with half maximal inhibitory concentrations (IC50) of 209.11 and 607.84 mg/L. Oridonin decreased heartbeat with IC50 of 285.76 mg/L at 48 hpf, and induced malformation at 120 hpf with half maximal effective concentration (EC50) of 411.94 mg/L. Oridonin also decreased body length with IC50 of 324.78 mg/L at 144 hpf, and increased swimming speed with ED50 of 190.98 mg/L at 120 hpf. The effects of oridonin on zebrafish embryo development may be attributed to the downregulation of VEGFR3 gene expression. Discussions and conclusions: Oridonin showed adverse effects at early stages of zebrafish development. We will perform additional studies on mechanism of oridonin based on VEGFR3.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 1388-0209
1744-5116
13880209
Relation: https://doaj.org/toc/1388-0209; https://doaj.org/toc/1744-5116
DOI: 10.1080/13880209.2019.1662457
Access URL: https://doaj.org/article/d85174392bf14bf5bb85a155e8cef6ba
Accession Number: edsdoj.85174392bf14bf5bb85a155e8cef6ba
Database: Directory of Open Access Journals
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More Details
ISSN:13880209
17445116
DOI:10.1080/13880209.2019.1662457
Published in:Pharmaceutical Biology
Language:English