利用斑马鱼模型和网络药理学研究荷丹胶囊血管保护作用的主要活性成分

Zebrafish model and network pharmacology platform were used to study the main active components of Hedan capsule for vascular protection

目的利用斑马鱼模型和网络药理学方法研究荷丹胶囊的血管保护作用主要活性成分,为后续深入研究提供科学依据。方法采用血管转基因标记的CZ55系斑马鱼为实验动物,评价荷丹胶囊对斑马鱼血管损伤的保护作用;通过中医药整合药理学研究平台TCMIP、TCMSP、Gencards数据库、String平台、Cytoscape软件构建荷丹胶囊中荷叶、丹参、山楂、番泻叶、补骨脂的主要化学成分与作用靶点的相互作用网络,并筛选中药活性成分,同时利用分子对接进行成分与靶点结合能评价,然后采用斑马鱼模型对筛选的活性成分进行二次验证。结果斑马鱼实验结果显示荷丹胶囊具有显著保护血管内皮损伤的作用;网络药理学筛选和分子对接结果提示丹参酮ⅡA、荷叶碱、补骨脂异黄酮醛、槲皮素可能是荷丹胶囊发挥药效的重要物质基础;斑马鱼实验结果显示,丹参酮ⅡA、槲皮素具有明显的血管保护活性。结论荷丹胶囊中丹参酮ⅡA、槲皮素可能是发挥血管保护作用的重要物质基础,具有多靶点整合调节的作用特点。

Objective Abstract:Objective To study the main active components of Hedan capsule by zebrafish model and network pharmacology method,and to provide reference for its clinical application.Methods CZ55 line zebrafish was used as experimental animals to evaluate the protective effect of Hedan capsule on drug-induced vascular injury.Through TCMIP,TCMSP,Gencards database,String platform and Cytoscape software,the interaction network of main chemical components and targets of Hedan capsule was constructed.Furthermore,the active components of traditional Chinese medicine were screened,and the binding energy of components to target was evaluated by molecular docking.Then the zebrafish model was used to validate the active components.Results The results of zebrafish experiment show that Hedan capsule has a significant protective effect on vascular endothelial injury.The network pharmacology screening and molecular docking suggested that tanshinone IIA,nuciferine,corylinal and quercetin might be the important material basis for the efficacy of Hedan capsule.The results of zebrafish experiment showed that tanshinone IIA and quercetin had obvious vascular protective activity.Conclusion Tanshinone IIA and quercetin in Hedan capsule might be the important material basis of vascular protection,and have the characteristics of multi-target integrated regulation.