Total Saponins of <italic style="font-style: italic">Panax notoginseng</italic> Activate Akt/mTOR Pathway and Exhibit Neuroprotection <italic style="font-style: italic">in vitro</italic> and <italic style="font-style: italic">in vivo</italic> against Ischemic Damage

Yu-wei PAN; Dong-ping WU; Hua-feng LIANG; Gen-yun TANG; Chun-lin FAN; Lei SHI; Wen-cai YE; Man-mei LI

doi:10.1007/s11655-021-3454-y

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Total Saponins of Panax notoginseng Activate Akt/mTOR Pathway and Exhibit Neuroprotection in vitro and in vivo against Ischemic Damage

Original Article | Updated：2022-06-27

- Total Saponins of Panax notoginseng Activate Akt/mTOR Pathway and Exhibit Neuroprotection in vitro and in vivo against Ischemic Damage
- Chinese Journal of Integrative Medicine Vol. 28, Issue 5, Pages: 410-418(2022)
- Affiliations：
  
  1.JNU-HKUST Joint Laboratory for Neuroscience and Innovative Drug Research, Jinan University, Guangzhou (510632), China
  2.Department of TCM Preventive Medicine, Tianhe District Hospital of Traditional Chinese Medicine, Guangzhou (510632), China
  3.Institute of Traditional Chinese Medicine and Natural Products,Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou (510632), China
- Author bio：
  
  Dr. LI Man-mei, E-mail: jnulimanmei1209@126.com
- Funds：
- DOI：10.1007/s11655-021-3454-y
  CLC：
- Published：01 May 2022，
  
  Published Online：28 September 2021，
  
  Accepted：10 May 2021
Scan for full text
Yu-wei PAN, Dong-ping WU, Hua-feng LIANG, et al. Total Saponins of Panax notoginseng Activate Akt/mTOR Pathway and Exhibit Neuroprotection in vitro and in vivo against Ischemic Damage. [J]. Chinese Journal of Integrative Medicine 28(5):410-418(2022)
DOI：

Yu-wei PAN, Dong-ping WU, Hua-feng LIANG, et al. Total Saponins of Panax notoginseng Activate Akt/mTOR Pathway and Exhibit Neuroprotection in vitro and in vivo against Ischemic Damage. [J]. Chinese Journal of Integrative Medicine 28(5):410-418(2022) DOI： 10.1007/s11655-021-3454-y.

摘要

目的:

揭示三七总皂苷 (TSPN) 在脑缺血再灌注损伤和皮层神经元细胞氧糖剥夺再灌注 (OGD/R) 中的神经保护作用及其作用机制.

方法:

在体外

通过MTT、流式和live/dead cell assay实验评估TSPN对神经元的保护作用

通过免疫荧光染色的方法观察突触的形态. 大脑中动脉阻塞 (MCAO) 是一种在小鼠体内模拟脑缺血再灌注的模型

通过神经评分、悬尾实验、TTC染色和尼氏染色的方法评估TSPN的神经保护作用. 通过Western blot、免疫组化和免疫荧光的方法检测TSPN对Akt/mTOR信号通路的影响.

结果:

在OGD/R模型中

MTT结果显示50

25及12.5 μg/mL TSPN能有效保护皮层神经元细胞 (

0.01 或

0.05)

流式和live/dead cell assay实验结果表明25 μg/mL TSPN 能抑制神经元细胞凋亡 (

0.05)

免疫荧光染色结果说明25 μg/mL TSPN 能恢复损伤皮层神经元细胞的形态 (

0.05) . 12.5 μg/mL TSPN 能抑制Beclin-1、Cleaved-caspase 3和LC3B-Ⅱ/LC3B-Ⅰ的升高

并且恢复p-Akt及p-mTOR的表达 (

0.01 或

0.05) . 在MCAO 模型中

50 μg/mL TSPN能改善小鼠的神经行为损伤并降低脑梗死体积 (

0.05)

减少Beclin-1及LC3B在缺血半暗带的表达

恢复p-mTOR的水平.

结论:

在OGD/R模型中

TSPN可能是通过缓解神经功能损伤并抑制神经元死亡

从而恢复突触完整性

保护神经元. TSPN发挥神经保护作用的机制可能是恢复p-mTOR抑制Beclin-1.

Abstract

Objective:

To reveal the neuroprotective effect and the underlying mechanisms of a mixture of the main components of

Panax notoginseng

saponins (TSPN) on cerebral ischemia-reperfusion injury and oxygenglucose deprivation/reoxygenation (OGD/R) of cultured cortical neurons.

Methods:

The neuroprotective effect of TSPN was evaluated by 3-(4

5-dimethylthiazol-2-yl)-2

5-diphenyl tetrazolium bromide (MTT) assay

flow cytometry and live/dead cell assays. The morphology of dendrites was detected by immunofluorescence. Middle cerebral artery occlusion (MCAO) was developed in rats as a model of cerebral ischemia-reperfusion. The neuroprotective effect of TSPN was evaluated by neurological scoring

tail suspension test

5-triphenyltetrazolium chloride (TTC) and Nissl stainings. Western blot analysis

immunohistochemistry and immunofluorescence were used to measure the changes in the Akt/mammalian target of rapamycin (mTOR) signaling pathway.

Results:

MTT showed that TSPN (50

25 and 12.5 μg/mL) protected cortical neurons after OGD/R treatment (

0.01 or

0.05). Flow cytometry and live/dead cell assays indicated that 25 μg/mL TSPN decreased neuronal apoptosis (

0.05)

and immunofluorescence showed that 25 μg/mL TSPN restored the dendritic morphology of damaged neurons (

0.05). Moreover

12.5 μg/mL TSPN downregulated the expression of Beclin-1

Cleaved-caspase 3 and LC3B-Ⅱ/LC3B-Ⅰ

and upregulated the levels of phosphorylated (p)-Akt and p-mTOR (

0.01 or

0.05). In the MCAO model

50 μg/mL TSPN improved defective neurological behavior and reduced infarct volume (

0.05). Moreover

the expression of Beclin-1 and LC3B in cerebral ischemic penumbra was downregulated after 50 μg/mL TSPN treatment

whereas the p-mTOR level was upregulated (

0.05 or

0.01).

Conclusions:

TSPN promoted neuronal survival and protected dendrite integrity after OGD/R and had a potential therapeutic effect by alleviating neurological deficits and reversing neuronal loss. TSPN promoted p-mTOR and inhibited Beclin-1 to alleviate ischemic damage

which may be the mechanism that underlies the neuroprotective activity of TSPN.

关键词

Keywords

total saponins of Panax notoginsengoxygen-glucose deprivation and reoxygenationneuroprotectionischemia-reperfusionAkt/mTOR pathwayChinese medicine

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Department of Neurology, The First Hospital of Quanzhou Affiliated to Fujian Medical University

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State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Science, Xiamen University

Fujian Pien Tze Huang Enterprise Key Laboratory of Natural Medicine Research and Development

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⁰

Total Saponins of Panax notoginseng Activate Akt/mTOR Pathway and Exhibit Neuroprotection in vitro and in vivo against Ischemic Damage

DOI：10.1007/s11655-021-3454-y

摘要

Abstract

关键词

Keywords

references