Panax notoginseng saponins promotes angiogenesis after cerebral ischemia-reperfusion injury

Ischemic stroke is a devastating disease that can result in permanent disability and death, and angiogenesis plays a critical role in the recovery and survival of patients and animal models of ischemic stroke. Panax notoginseng has been used as a key herb in the treatment of stroke diseases due to its effect in promoting blood circulation and removing blood stasis. However, the role of Panax notoginseng saponins, in promoting angiogenesis is unclear. This study is aimed to investigate the effect of Xueshuantong (XST) injection, composed of Panax notoginseng saponins in post-stroke revascularization. In the present study, a middle cerebral artery occlusion/reperfusion model was established in Sprague-Dawley rats, with XST and the positive drug Dl-3-n-butylphthalide (NBP) administered via intraperitoneal injection to observe vascular changes after stroke. The protective and pro-angiogenic effects of XST after stroke were demonstrated by Triphenyltetrazolium chloride staining and optical coherence tomography angiography. Subsequently, network pharmacology and molecular docking techniques, as well as experimental validation, were used to further analyze the potential mechanism by which XST promotes angiogenesis. The results showed that XST could reduce the cerebral infarction region in rats. And the neovascularization in the ischemic area of the rat brain significantly increased after 7 or 14 days of XST administration. Furthermore, XST could activate the vascular endothelial growth factor A (VEGFA)/vascular endothelial growth factor receptor 2 (VEGFR2), and hypoxia-inducible factor 1 (HIF-1) signaling pathways. XST may promote post-stroke angiogenesis by affecting the HIF1-α/VEGFA/VEGFR2 signaling pathways.