• Junmin Chen, Xiangjian Zhang, Xiaoxia Liu, Cong Zhang, Wenyan Shang, Jing Xue, Rong Chen, Yuan Xing, Degang Song, and Renhao Xu.
• Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, China; Hebei Key Laboratory of Vascular Homeostasis and Hebei Collaborative Innovation Center for Cardio-cerebrovascular Disease, 215 Hepingxi Road, Shijiazhuang, Hebei, 050000, China.
• Eur. J. Pharmacol. 2019 Aug 5; 856: 172418.

AbstractAngiogenesis plays an important role in the remodeling process of the ischemic brain and the recovery of neurological function after ischemic stroke. Ginsenoside Rg1 has been reported to exert neuroprotective effects on the central nervous system. However, the effects of ginsenoside Rg1 on cerebral angiogenesis in cerebral ischemia remained unclear. The current study aimed to investigate the potential protective effects of ginsenoside Rg1 on cerebral angiogenesis as well as its underlying mechanisms. Mice were subjected to treatment with vehicle or ginsenoside Rg1 daily for 14 d beginning at 24 h after distal middle cerebral artery occlusion (dMCAO). Compared with the dMCAO group, ginsenoside Rg1 improved the neurobehavioral outcomes and reduced the brain infarct volume. Ginsenoside Rg1 treatment increased the expression of the cluster of differentiation 31 (CD31), bromodeoxyuridine+/CD31+ microvessels and GFAP-positive vessels in the peri-infarct cortex. The expression of VEGF was significantly enhanced in ginsenoside Rg1 group. In vitro, human brain microvascular endothelial (hCMEC/D3) cells was successfully cultured, and oxygen and glucose deprivation (OGD) model was established. Ginsenoside Rg1 significantly increased proliferation, migration and tube formation of endothelial cells after OGD, as well as upregulated the expressions of VEGF, HIF-1α, PI3K, p-Akt, and p-mTOR. Furthermore, administration of PI3K/Akt/mTOR signaling pathway inhibitor LY294002 abolished the beneficial effects of ginsenoside Rg1. In conclusion, ginsenoside Rg1 promoted cerebral angiogenesis through increasing the expression of VEGF via PI3K/Akt/mTOR signaling pathway after ischemic stroke.Copyright © 2019. Published by Elsevier B.V.

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