Modified Renshen Yangrong decoction enhances angiogenesis in ischemic stroke through promotion of MicroRNA-210 expression by regulating the HIF/VEGF/Notch signaling pathway.

Abstract

ObjectiveThis study aims to investigate the efficacy of modified Ginseng Yangrong decoction (GSYRD) promoting angiogenesis after ischemic stroke.MethodsIn an in vivo study, rats that survived surgery were allocated into four groups: the control group and model group were treated with normal saline, the GSYRD group was treated with 18.9 mg/kg of GSYRD daily, and the positive control group was treated with Tongxinluo (TXL) (1 g/kg/d). At the end of the seven‐day treatment, the area of cerebral infarction, the expression changes of miRNA‐210 and ephrin A3 were determined. In an in vitro study, HUVECs were divided into a normal control serum group (NC group), normal control serum OGD group (Oxygen Glucose Deprivation group) (OGD group), OGD + drug‐containing serum group (OGD+GSYRD group), and OGD + drug‐containing serum + ES group (Endostatin group) (OGD+GSYRD+ES group). The cells in all groups except the NC group were cultured in a sugar‐free DMEM medium under hypoxia for 48 h. Cell proliferation, angiogenic structure formation ability, the expression changes of miRNA‐210, ephrin A3, and the HIF/VEGF/Notch signaling pathway‐related molecules were determined.ResultsIn vivo, GSYRD significantly reduced infarct size (p < .01), the expression of miRNA‐210 and ephrin A3 were decreased in the GSYRD group (p < .05). In vitro, the cell proliferation and tube formation ability were significantly increased in the GSYRD group (p < .05), and the expression of miRNA‐210 and ephrin A3 was decreased (p < .05). In addition, in the GSYRD group, the expression of the HIF/VEGF/Notch signaling pathway‐related molecules was significantly increased (p < .01 or p < .05).ConclusionGSYRD promotes cerebral protection following angiogenesis and ischemic brain injury. The specific mechanism was activating the HIF/VEGF/Notch signaling pathway via miRNA‐210.