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

Abstract

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.This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

tsRNA-15797-modified BMSC-derived exosomes mediate LFNG to induce angiogenesis in osteonecrosis of the femoral head

“…We have previously found that 86 exosomal tsRNA was down-regulated in the plasma of ONFH patients compared with the healthy individuals by small RNA sequencing ( Fang et al, 2020 ). To further investigate the molecular mechanism of exosomal tsRNA involved in angiogenesis of ONFH, we finally screened tsRNA-15797 and tsRNA-10520, according to the evidence that their target genes were involved in angiogenesis-related pathways, including HIF-1α signaling pathway ( Zhang et al, 2018 ), VEGF signaling pathway ( Liang et al, 2021 ), Wnt signaling pathway ( Jiang et al, 2015 ) and TGF-beta signaling pathway ( Wang et al, 2013 ) ( Figure S1 ). Subsequently, to further verify the expression of tsRNA-15797 and tsRNA-10520 in plasma exosomes from ONFH patients, we first isolated exosomes derived from plasma of ONFH patients and healthy subjects, and comprehensively characterized the morphologies and structures of exosomes by TEM and NTA methods.…”

Network pharmacology-based and experimental identification of the effects of Renshen Yangrong decoction on myocardial infarction

“…To investigate the effects of RSYRD on MI, experimental mice were divided into four groups: the SHAM group, in which the mice with thoracotomy were intragastrically administered normal saline (NS); the SHAM + RSYRD group (SHAM + R), in which the mice with thoracotomy were intragastrically administered with RSYRD; the LAD ligated group (MI), in which the mice with LAD ligation were intragastrically administered NS; and the MI + RSYRD group (MI + R), in which the mice with LAD ligation were intragastrically administered with RSYRD. According to previous studies, RSYRD was intragastrically administered at a dose of 38 g/kg per day to the SHAM + R and MI + R groups for 3 days following surgery ( Liang et al, 2021 ).…”

“…Previous research have indicated that RSYRD can inhibit platelet activity in patients with ischemic heart disease and promote the proliferation, migration, and DNA synthesis of human umbilical vein endothelial cells ( Sheng et al, 2019 ). Remarkably, RSYRD has been shown to promote angiogenesis and cerebral protection following ischemic brain injury by activating the HIF/VEGF/NOTCH signaling pathway via miRNA-210 ( Liang et al, 2021 ). These findings suggest that RSYRD may have a protective role in MI.…”

Recent advances in tissue repair of the blood-brain barrier after stroke

“… 144 New researches show that GSYRD can activate HIF/VEGF/Notch signaling pathway through miR-210 to achieve enhanced angiogenesis after cerebral ischemia. 145 …”