Preliminary safety assessment of oridonin in zebrafish

Abstract

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.

Keywords:

• Isodon rubescens
• medicinal plant
• embryonic development effects
• body length
• swimming speed
• VEGFR3

Acknowledgements

The authors sincerely appreciate the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences for providing the zebrafish.

Disclosure statement

The authors declare no conflicts of interest.

Additional information

Funding

This study was supported by the state administration of the famous Chinese Medicine Expert Qian Bowen’s Inheritance Studio. This project was supported by Zhejiang Hospital Technology Project Foundation [No. 2016] and Zhejiang Province Traditional Chinese Medicine Science and Technology Project Foundation [No. 2018ZQ002].