This study aims to investigate the key active components with protection potential on endothelial injury in green prickly ash by using a zebrafish model and network pharmacology technology.A vascular endothelial injury model was established using a transgenic zebrafish to evaluate the activity of green prickly ash extract.The potential active components were screened using network pharmacology protein-protein interaction network methods and molecular docking techniques.Then, the protective effect against vascular endothelial injury of the candidate components was evaluated by the zebrafish model again.Zebrafish experiments showed that the green prickly ash extract can significantly promote the diameter of intersegmental blood vessels in zebrafish, indicating a certain level of vascular endothelial protection.The four components (quercetin, skimmianine, diosmetin and kokusaginine) in green prickly ash were screened to have strong binding affinity with the core target GAPDH by the network pharmacology and molecular docking techniques.And the zebrafish results demonstrated that diosmetin and quercetin displayed significant protective effects against vascular endothelial injury.In summary, this study firstly identified that skimmianine and quercetin in green prickly ash are key pharmacologically active components exerting protective effects against vascular endothelial injury.These findings provide a theoretical basis for the development and utilization of green prickly ash resources and their clinical scientific applications.