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

IF 4.6 2区医学 Q1 NEUROSCIENCES

Neuropharmacology Pub Date : 2024-11-16 DOI:10.1016/j.neuropharm.2024.110226

Daiju Tao, Fajing Li, Xiaochao Zhang, Hui Guo, Renhua Yang, Yuan Yang, Li Zhang, Zhiqiang Shen, Jia Teng, Peng Chen, Bo He

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引用次数: 0

Abstract

Objective: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

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20(R)-人参皂苷Rg3通过PI3K/Akt/mTOR信号通路抑制自噬，从而防止局灶性脑缺血再灌注损伤。

研究目的本研究旨在探讨20(R)-人参皂苷Rg3对大鼠脑缺血再灌注损伤（CIRI）诱导的自噬的影响，并探讨其对PI3K/Akt信号通路的调控作用：方法：雄性大鼠在建模前12小时、缺血后2小时和再灌注后12小时腹腔注射20(R)-金森甙Rg3（5、10、20 mg/kg），进行大脑中动脉闭塞/再灌注（MCAO/R）。脑缺血/再灌注24小时后检测神经行为和神经元形态学变化。在体外，在 PC12 细胞中复制 OGD/R 诱导的损伤模型，并给予不同浓度的 20(R)-ginsenoside Rg3，观察其对细胞活力、自噬和 PI3K/Akt/mTOR 相关蛋白表达的影响：我们的研究结果表明，与MCAO/R组相比，20 mg/kg 20（R）-人参皂苷Rg3能显著减轻神经元损伤，表现为受损神经元数量减少、Nissl细胞团溶解减少、自噬体减少以及Beclin1和LC3-II/I表达下调。此外，20(R)-金森甙 Rg3 还能显著上调 p62、p-PI3K、p-AKT 和 p-mTOR 的表达。在体外，20（R）-人参皂苷 Rg3 能明显提高 OGD/R 后细胞的存活率，并能明显减弱 LY294002 和 OGD/R 诱导的 Beclin1 和 LC3 基因表达上调。此外，20（R）-人参皂苷 Rg3 还能挽救 LY294002 和 OGD/R 诱导的 p62、p-PI3K、p-AKT 和 p-mTOR 表达下调：结论：20(R)-人参皂苷Rg3通过抑制自噬的激活减轻缺血再灌注后的神经元损伤和运动功能障碍，其机制与PI3K/Akt/mTOR信号通路的上调有关。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Neuropharmacology 医学-神经科学

CiteScore

10.00

自引率

4.30%

发文量

288

审稿时长

45 days

期刊介绍： Neuropharmacology publishes high quality, original research and review articles within the discipline of neuroscience, especially articles with a neuropharmacological component. However, papers within any area of neuroscience will be considered. The journal does not usually accept clinical research, although preclinical neuropharmacological studies in humans may be considered. The journal only considers submissions in which the chemical structures and compositions of experimental agents are readily available in the literature or disclosed by the authors in the submitted manuscript. Only in exceptional circumstances will natural products be considered, and then only if the preparation is well defined by scientific means. Neuropharmacology publishes articles of any length (original research and reviews).