背景:研究证实,大剂量冰片具有围产期毒性,对胚胎发育有一定影响。然而,关于冰片对斑马鱼胚胎发育的影响很少。因此,我们比较了D-冰片的效果,L-冰片和合成冰片对斑马鱼胚胎生长发育的影响,并预测了围产期毒性的可能机制。
方法:胚胎死亡率,孵化率,以48hpf记录各组心率,比较冰片对斑马鱼胚胎发育的影响。利用网络药理学和分子对接技术预测围产期毒性的可能机制。
结果:我们发现冰片在24和48hpf时增加了死亡率,在24hpf时抑制自主运动行为,并影响48hpf的孵化率和心率。网络药理学分析显示,冰片在围生期具有相同的毒性靶点,通过调节肿瘤通路参与调节围生期毒性,化学致癌-受体激活,PI3K-Akt等。分子对接表明活性成分与核心靶标的结合活性处于中等水平,冰片活性成分与核心靶标的结合活性差异不大。
结论:三种冰片对斑马鱼胚胎发育的影响不同。L-冰片的毒性最低。围产期毒性的机制与炎症有关,凋亡,细胞周期和生长,分化和繁殖。
BACKGROUND: Studies have confirmed that high dose borneol has perinatal toxicity and has a certain effect on embryonic development. However, there is little about the effect of borneol on the development of zebrafish embryos. Therefore, we compared the effects of D-borneol, L-borneol and synthetic borneol on the growth and development of zebrafish embryos, and predicted the possible mechanism of perinatal toxicity.
METHODS: The embryonic mortality rate, hatching rate, and heart rate of each group were recorded at 48 hpf to compare the effects of borneols on the development of zebrafish embryos. Network pharmacology and molecular docking technology were used to predict the possible mechanism of perinatal toxicity.
RESULTS: We found that borneols increased the mortality at 24 and 48 hpf, inhibited the autonomous movement behavior at 24 hpf, and affected the hatching rate and heart rate at 48 hpf. Network pharmacology analysis showed that borneols had the same toxic targets in the perinatal period and were involved in regulating perinatal toxicity by regulating pathways in cancer, chemical carcinogenesis-receptor activation, PI3K-Akt and others. Molecular docking showed that the binding activity of the active ingredients and the core target was at a medium level, and the binding activity of the borneols active ingredients and the core target was not much different.
CONCLUSIONS: Three kinds of borneol on the development of zebrafish embryos were different. The toxicity of L-borneol was the lowest. The mechanisms of perinatal toxicity were related to inflammation, apoptosis, cell cycle and growth, differentiation and reproduction.