Astragaloside IV regulates the HIF/VEGF/Notch signaling pathway through miRNA-210 to promote angiogenesis after ischemic stroke.
Restor Neurol Neurosci. 2020 May 12. Epub 2020 May 12. PMID: 32417803
BACKGROUND: Astragaloside IV (AS-IV) is one of the main active ingredients of Astragalusmembranaceus. Studies have shown that AS-IV stimulates angiogenesis, including cell proliferation, migration, and neovascularization. However, the relevant mechanism remains unclear.
OBJECTIVE: This study aims to investigate whether AS-IV activates the HIF/VEGF/Notch signaling pathway through miRNA-210 to promote angiogenesisafter ischemic stroke.
METHODS: The present study established a rat model of middle cerebral artery occlusion (MCAO) and cultured human umbilical vein endothelial cells (HUVECs) under hypoxic conditions in vitro to investigate the role of AS-IV in promoting angiogenesis and reveal its underlying mechanism. Through in vivo studies, the area of cerebral infarction was determined by 2,3,5-triPhenyltetrazolium chloride (TTC) staining. Immunofluorescence staining and RT-qPCR were used to detect the expression changes of miRNA-210 and ephrinA3 in the ischemic cortex after ischemia. Through in vitro studies, cell proliferation was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Subsequently, angiogenesis experiments were performed to observe the angiogenic ability.
RESULTS: Results revealed that AS-IV significantly reduced infarct size, promoted cell proliferation and ductal formation, and inhibited the expression of the target gene ephrinA3 by increasing the expression of miRNA-210 and inducing activation of the HIF-VEGF-Notch signaling pathway.
CONCLUSIONS: AS-IV promotes cerebral protection following angiogenesis and ischemic brain injury. The specific mechanism was activating the HIF/VEGF/Notch signaling pathway via miRNA-210.