Preliminary safety assessment of oridonin in zebrafish.

Oridonin, isolated from the leaves of (Hemsl.) H.Hara (Lamiaceae), has good antitumor activity. However, its safety is still unclear. To investigate the preliminary safety of oridonin in zebrafish. Embryo, larvae and adult zebrafish ( = 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. , and gene expression were also examined. Low-dose oridonin increased spontaneous movement and hatching rate with median effective doses (ED) 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 (IC) of 209.11 and 607.84 mg/L. Oridonin decreased heartbeat with IC of 285.76 mg/L at 48 hpf, and induced malformation at 120 hpf with half maximal effective concentration (EC) of 411.94 mg/L. Oridonin also decreased body length with IC of 324.78 mg/L at 144 hpf, and increased swimming speed with ED of 190.98 mg/L at 120 hpf. The effects of oridonin on zebrafish embryo development may be attributed to the downregulation of gene expression. Oridonin showed adverse effects at early stages of zebrafish development. We will perform additional studies on mechanism of oridonin based on VEGFR3.