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Magnolol Protects Against Oxidative Stress-Mediated Neural Cell Damage by Modulating Mitochondrial Dysfunction and PI3K/Akt Signaling

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Abstract

Magnolol, an orally available compound from Magnolia officinalis used widely in traditional herbal medicine against a variety of neuronal diseases, possesses potent antioxidant properties and protects the brain against oxidative damage. The aim of the work is to examine the protective mechanisms of magnolol on human neuroblastoma SH-SY5Y cells against apoptosis induced by the neurotoxin acrolein, which can cause neurodegenerative disorders by inducing oxidative stress. By investigating the effect of magnolol on neural cell damage induced by the neurotoxin acrolein, we found that magnolol pretreatment significantly attenuated acrolein-induced oxidative stress through inhibiting reactive oxygen species accumulation caused by intracellular glutathione depletion and nicotinamide adenine dinucleotide phosphate oxidase activation. We next examined the signaling cascade(s) involved in magnolol-mediated antiapoptotic effects. The results showed that acrolein induced SH-SY5Y cell apoptosis by activating mitochondria/caspase and MEK/ERK signaling pathways. Our findings provide the first evidence that magnolol protects SH-SY5Y cells against acrolein-induced oxidative stress and prolongs SH-SY5Y cell survival through regulating JNK/mitochondria/caspase, PI3K/MEK/ERK, and PI3K/Akt/FoxO1 signaling pathways.

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Abbreviations

3-NT:

3-Nitrotyrosine

4-HNE:

4-Hydroxynonenal

AD:

Alzheimer’s disease

Akt:

Protein kinase B

ERK:

Extracellular signal-regulated kinase

FoxO:

O subfamily of forkhead transcription factors

GSH:

Glutathione

GSSG:

Disulfide oxidized glutathione

HNE:

Hydroxynonenal

JNK/SAPK:

c-Jun N-terminal kinase/stress-activated protein kinase

MEK:

Mitogen-activated protein kinase kinase

NADPH:

Nicotinamide adenine dinucleotide phosphate

PD:

Parkinson’s disease

PI3K:

Phosphatidylinositol 3-kinase

ROS:

Reactive oxygen species

ΔΨm:

Mitochondrial membrane potential

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Acknowledgments

This work was supported by the China National “12.5” Foundation (no. 2011BAJ07B04) and the Open Foundation (SKLODSCUKF2012-04) from the State Key Laboratory of Oral Diseases, Sichuan University for the financial support and National Natural Science Foundation of China (no. 20972105 and 20772087) and Sichuan Province Foundation (no. 2008SZ0024).

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Authors and Affiliations

  1. Laboratory of Ethnopharmacology, Regenerative Medicine Research Center, West China Hospital, West China Medical School, and Institute for Nanobiomedical Technology and Membrane Biology, Sichuan University, No. 1 Keyuansilu, Gaopeng Dadao, Chengdu, Sichuan, 610041, People’s Republic of China

    Liqun Dong, Yang He & Wen Huang

  2. Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China

    Liqun Dong

  3. Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China

    Shu Zhou & Xiaohua Yang

  4. State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China

    Qianming Chen

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  1. Liqun Dong
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  2. Shu Zhou
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  3. Xiaohua Yang
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  4. Qianming Chen
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  5. Yang He
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  6. Wen Huang
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Corresponding authors

Correspondence to Qianming Chen, Yang He or Wen Huang.

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Liqun Dong and Shu Zhou contributed equally to this work.

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Dong, L., Zhou, S., Yang, X. et al. Magnolol Protects Against Oxidative Stress-Mediated Neural Cell Damage by Modulating Mitochondrial Dysfunction and PI3K/Akt Signaling. J Mol Neurosci 50, 469–481 (2013). https://doi.org/10.1007/s12031-013-9964-0

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  • DOI: https://doi.org/10.1007/s12031-013-9964-0

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