Preliminary safety assessment of oridonin in zebrafish

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...

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Autores principales:	Lili Tian, Donglai Sheng, Qiushuang Li, Chenxu Guo, Guofu Zhu
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2019
Materias:	isodon rubescens medicinal plant embryonic development effects body length swimming speed vegfr3 Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/d85174392bf14bf5bb85a155e8cef6ba
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spelling	oai:doaj.org-article:d85174392bf14bf5bb85a155e8cef6ba2021-11-17T14:21:56ZPreliminary safety assessment of oridonin in zebrafish1388-02091744-511610.1080/13880209.2019.1662457https://doaj.org/article/d85174392bf14bf5bb85a155e8cef6ba2019-01-01T00:00:00Zhttp://dx.doi.org/10.1080/13880209.2019.1662457https://doaj.org/toc/1388-0209https://doaj.org/toc/1744-5116Context: 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.Lili TianDonglai ShengQiushuang LiChenxu GuoGuofu ZhuTaylor & Francis Grouparticleisodon rubescensmedicinal plantembryonic development effectsbody lengthswimming speedvegfr3Therapeutics. PharmacologyRM1-950ENPharmaceutical Biology, Vol 57, Iss 1, Pp 632-640 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	isodon rubescens medicinal plant embryonic development effects body length swimming speed vegfr3 Therapeutics. Pharmacology RM1-950
spellingShingle	isodon rubescens medicinal plant embryonic development effects body length swimming speed vegfr3 Therapeutics. Pharmacology RM1-950 Lili Tian Donglai Sheng Qiushuang Li Chenxu Guo Guofu Zhu Preliminary safety assessment of oridonin in zebrafish
description	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.
format	article
author	Lili Tian Donglai Sheng Qiushuang Li Chenxu Guo Guofu Zhu
author_facet	Lili Tian Donglai Sheng Qiushuang Li Chenxu Guo Guofu Zhu
author_sort	Lili Tian
title	Preliminary safety assessment of oridonin in zebrafish
title_short	Preliminary safety assessment of oridonin in zebrafish
title_full	Preliminary safety assessment of oridonin in zebrafish
title_fullStr	Preliminary safety assessment of oridonin in zebrafish
title_full_unstemmed	Preliminary safety assessment of oridonin in zebrafish
title_sort	preliminary safety assessment of oridonin in zebrafish
publisher	Taylor & Francis Group
publishDate	2019
url	https://doaj.org/article/d85174392bf14bf5bb85a155e8cef6ba
work_keys_str_mv	AT lilitian preliminarysafetyassessmentoforidonininzebrafish AT donglaisheng preliminarysafetyassessmentoforidonininzebrafish AT qiushuangli preliminarysafetyassessmentoforidonininzebrafish AT chenxuguo preliminarysafetyassessmentoforidonininzebrafish AT guofuzhu preliminarysafetyassessmentoforidonininzebrafish
_version_	1718425513302687744

Preliminary safety assessment of oridonin in zebrafish

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