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Astragaloside IV prevents MPP+-induced SH-SY5Y cell death via the inhibition of Bax-mediated pathways and ROS production

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Abstract

Parkinson’s disease (PD) is characterized by a progressive degeneration of dopaminergic neurons in the substantia nigra. Oxidative stress and neural degeneration are suggested to be involved in the pathogenesis of PD. Previous studies have revealed that Astragaloside IV (AS-IV) can reduce inflammation and oxidation, making it a potential therapeutic agent for neurodegenerative disease. In this study, we investigated whether AS-IV protect against 1-methyl-4-phenylpyridnium ion (MPP+)-induced dopaminergic neurotoxicity in SH-SY5Y cells and determined the mechanism of AS-IV neuroprotection. We found that pretreatment with AS-IV significantly reversed the loss of cell viability, nuclear condensation, the generation of intracellular reactive oxygen species (ROS), and the increase in Bax/Bcl-2 ratio and the activity of caspase-3 induced by MPP+. Our study suggests that the neuroprotective effect of AS-IV is related to mechanisms including ROS production and the inhibition of Bax-mediated pathway. The present study supports the notion that AS-IV may be a promising neuroprotective agent for the treatment of neurodegenerative disorders such as PD.

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Abbreviations

AS-IV:

Astragaloside IV

DCF:

Dichlorofluorescein

GPs:

Gypenosides

MPP+ :

1-Methyl-4-phenylpyridnium ion

MPT:

Mitochondrial permeability transition

MPTP:

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine

PD:

Parkinson’s disease

ROS:

Reactive oxygen species

SN:

Substantia nigra

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Authors and Affiliations

  1. Department of Neurosurgery and Institute for Functional Brain Disorders, Tangdu Hospital, The Fourth Military Medical University, 1 Xinsi Road, Baqiao District, Xi’an, People’s Republic of China

    Zhi-guo Zhang, Ju-lei Wang, Li-hong Li, Yi Xia, Huai-zhou Qin & Guo-dong Gao

  2. Department of Biochemistry and Molecular Biology, State Key Laboratory of Cancer Biology, The Fourth Military Medical University, Xi’an, People’s Republic of China

    Lin Wu, Jing Zhang, Jian Zhang & Li-bo Yao

  3. Department of Hepatobiliary Surgery, Xijing Hospital, The Fourth Military Medical University, Xi’an, People’s Republic of China

    Jian-dong Yang

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  1. Zhi-guo Zhang
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  2. Lin Wu
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  3. Ju-lei Wang
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Corresponding authors

Correspondence to Huai-zhou Qin or Guo-dong Gao.

Additional information

The first four authors contributed equally to this work.

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Supplement Fig. 1 Chemical structure of astragaloside IV (TIFF 427 kb)

11010_2011_1219_MOESM2_ESM.tif

Supplement Fig. 2 To select AS-IV concentrations for the subsequent experiments, MTT analysis was performed on SH-SY5Y cells. SH-SY5Y cells were treated with 0–200 μM AS-IV for 24 h (TIFF 570 kb)

11010_2011_1219_MOESM3_ESM.tif

Supplement Fig. 3 To select MPP+ concentrations for the subsequent experiments, MTT analysis was performed on the MPP+-induced SH-SY5Y cells. SH-SY5Y cells were treated with 0–6 mM MPP+ for 24 h (TIFF 502 kb)

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Zhang, Zg., Wu, L., Wang, Jl. et al. Astragaloside IV prevents MPP+-induced SH-SY5Y cell death via the inhibition of Bax-mediated pathways and ROS production. Mol Cell Biochem 364, 209–216 (2012). https://doi.org/10.1007/s11010-011-1219-1

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