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20(R)-ginsenoside Rg3 protects against focal cerebral ischemia‒reperfusion injury by suppressing autophagy via PI3K/Akt/mTOR signaling pathway

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机构: [1]School of Pharmaceutical Science, Yunnan Key Laboratory of Pharmacology for Natural Products, NHC Key Laboratory of Drug Addiction Medicine, Kunming Medical University, Kunming, 650500, PR China. [2]The First People's Hospital of Liangshan Yi Autonomous Prefecture, XiChang, Sichuan Province, 615000, PR China. [3]Department of Pharmacology, Haiyuan College, Kunming Medical University, 650106, PR China.
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关键词: 20(R)-Ginsenoside Rg3 Cerebral ischemia‒reperfusion Autophagy PI3K/Akt signaling pathway

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This study aimed to investigate the effect of 20(R)-ginsenoside Rg3 on autophagy induced by cerebral ischemia‒reperfusion injury (CIRI) in rats and explore its regulation of the PI3K/Akt signaling pathway.Middle cerebral artery occlusion/reperfusion (MCAO/R) in male rats was injected intraperitoneally with 20(R)-ginsenoside Rg3 (5, 10, 20 mg/kg) 12 h before modeling, 2 h after ischemia and 12 h after reperfusion. Neurobehavioral and neuronal morphological changes were detected 24 h after brain I/R. In vitro, the OGD/R-induced injury model is replicated in PC12 cells and different concentrations of 20(R)-ginsenoside Rg3 are administered to observe its effects on cell viability and autophagy and PI3K/Akt/mTOR-related protein expression.Our findings suggest that treatment with 20 mg/kg 20(R)-ginsenoside Rg3 significantly attenuated the neuronal injury, as evidenced by a decreased number of damaged neurons, reduced dissolution of Nissl corpuscles, a fewer autophagosomes, and downregulated expression of Beclin1 and LC3-II/I compared with the MCAO/R group. Furthermore, 20(R)-ginsenoside Rg3 treatment significantly upregulated the expression of p62, p-PI3K, p-AKT, and p-mTOR. In vitro, 20(R)-ginsenoside Rg3 significantly improved the survival rate of cells following OGD/R and markedly attenuated the LY294002 and OGD/R-induced upregulation of Beclin1 and LC3 gene expression. Moreover, 20(R)-ginsenoside Rg3 could rescued the LY294002 and OGD/R-induced downregulation of p62, p-PI3K, p-AKT, and p-mTOR expression.20(R)-ginsenoside Rg3 attenuates neuronal injury and motor dysfunction following ischemia-reperfusion by inhibiting the activation of autophagy, and its mechanism is related to the upregulation of the PI3K/Akt/mTOR signaling pathway.Copyright © 2024 Elsevier Ltd. All rights reserved.

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大类 | 2 区 医学
小类 | 2 区 药学 3 区 神经科学
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第一作者机构: [1]School of Pharmaceutical Science, Yunnan Key Laboratory of Pharmacology for Natural Products, NHC Key Laboratory of Drug Addiction Medicine, Kunming Medical University, Kunming, 650500, PR China.
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通讯机构: [1]School of Pharmaceutical Science, Yunnan Key Laboratory of Pharmacology for Natural Products, NHC Key Laboratory of Drug Addiction Medicine, Kunming Medical University, Kunming, 650500, PR China. [3]Department of Pharmacology, Haiyuan College, Kunming Medical University, 650106, PR China.
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