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

Ce Liang; Teng Zhang; Xu-Liang Shi; Lin Jia; Ya-Li Wang; Cui-Huan Yan

doi:10.1002/brb3.2295

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

Brain Behav. 2021 Aug;11(8):e2295. doi: 10.1002/brb3.2295. Epub 2021 Aug 1.

Authors

Ce Liang¹, Teng Zhang², Xu-Liang Shi³, Lin Jia⁴, Ya-Li Wang⁵, Cui-Huan Yan⁶

Affiliations

¹ Department of Hebei TCM Formula Granule Innovation Center, Hebei University of Chinese Medicine, Shijiazhuang, China.
² Department of Health Commission of Hebei Province, Department of Health of Traditional Chinese Medicine, Shijiazhuang, China.
³ Department of Acupuncture and Moxibustion, Hebei University of Chinese Medicine, Shijiazhuang, China.
⁴ Department of Respiratory, Hebei Provincial Hospital of Traditional Chinese Medicine, Shijiazhuang, China.
⁵ Department of Teaching and Research Section of Integrative Medicine, Hebei Medical University, Shijiazhuang, China.
⁶ Department of Internal Medicine, Hebei University of Chinese Medicine, Shijiazhuang, China.

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.

Keywords: HIF/VEGF/Notch; Ischemic stroke; Renshen Yangrong decoction; angiogenesis; miRNA-210.

MeSH terms

Animals
Brain Ischemia* / drug therapy
Drugs, Chinese Herbal
Ischemic Stroke*
MicroRNAs* / genetics
Rats
Signal Transduction
Stroke* / drug therapy
Vascular Endothelial Growth Factor A

Substances

Drugs, Chinese Herbal
MIRN210 microRNA, rat
MicroRNAs
Vascular Endothelial Growth Factor A
renshen yangrong decoction