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

OBJECTIVE: This study aims to investigate the efficacy of modified Ginseng Yangrong decoction (GSYRD) promoting angiogenesis after ischemic stroke. METHODS: In 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. RESULTS: In 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). CONCLUSION: GSYRD promotes cerebral protection following angiogenesis and ischemic brain injury. The specific mechanism was activating the HIF/VEGF/Notch signaling pathway via miRNA‐210.