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Ethanolic Extract of Fructus Alpinia oxyphylla Protects Against 6-Hydroxydopamine-Induced Damage of PC12 Cells In Vitro and Dopaminergic Neurons in Zebrafish

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Abstract

In an attempt to understand the neuroprotective effect of Fructus Alpinia oxyphylla (AOE) and to elucidate its underlying mechanism of action, the ethanolic extract of AOE was investigated using zebrafish and PC12 cell models. AOE prevented and restored 6-hydroxydopamine (6-OHDA)-induced dopaminergic (DA) neuron degeneration and attenuated a deficit of locomotor activity in a zebrafish (Danio rerio) model of Parkinson’s disease (PD). Treatment with AOE increased the viability of 6-OHDA-treated PC12 cells in vitro in a dose-dependent manner by attenuating cellular apoptosis. However, protocatechuic acid (PCA) and chrysin, two known polyphenol components of AOE, could not reproduce the neuroprotective activity of AOE in the PD zebrafish or PC12 cell models. A mechanistic study found that the protective effect of AOE against 6-OHDA-induced neuronal injury involved anti-inflammatory action (down-regulation of gene expression of IL-1β and TNF-α) and anti-oxidative action (inhibition of NO production and iNOS expression in PC12 cells). Moreover, the PI3K-AKT pathway might be part of the mechanism of neuroprotection of AOE. The results of this research are expected to provide a scientific rationale for the use of AOE in the treatment of PD. However, it is important that the active components that contribute to the neuroprotective action of AOE are identified and characterized.

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Abbreviations

AOE:

Ethanolic extract of Fructus Alpinia oxyphylla

PCA:

Protocacheuic acid

F-12K:

Kaighn’s modification of Ham’s F12 medium

MTT:

3-(4,5-Dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium bromide

FBS:

Fetal bovine serum

DMSO:

Dimethyl sulfoxide

PBS:

Phosphate-buffered saline

6-OHDA:

6-Hydroxydopamine

IL-1b:

Interleukin 1 beta

TNF-a:

Tumor necrosis factor alpha

l-NAME:

Nω-nitro-l-arginine methyl ester hydrochloride

SNP:

Sodium nitroprusside dehydrate

CNS:

Central nervous system

PD:

Parkinson’s disease

DA:

Dopaminergic

dpf:

Days post fertilization

nom:

Nomifensine

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Acknowledgments

This work was supported by a grant from the Science and Technology Development Fund of Macau SAR (Ref. No. 045/2007/A3) and the Research Committee, University of Macau (Ref. No. UL017/09-Y1).

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Authors and Affiliations

  1. State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Av. Padre Toma’s Pereira S.J. Taipa, Macao SAR, China

    Zai-Jun Zhang, Lorita C. V. Cheang, Mei-Wei Wang & Simon M. Y. Lee

  2. Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine & New Drug Research, Institute of New Drug Research, Jinan University College of Pharmacy, Guangzhou, China

    Zai-Jun Zhang

  3. Department of Chemistry, The University of Hong Kong, Hong Kong SAR, China

    Guo-Hui Li & Ivan K. Chu

  4. School of Chinese Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR

    Zhi-Xiu Lin

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  1. Zai-Jun Zhang
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  2. Lorita C. V. Cheang
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  3. Mei-Wei Wang
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  4. Guo-Hui Li
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  5. Ivan K. Chu
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  7. Simon M. Y. Lee
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Correspondence to Simon M. Y. Lee.

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Zhang, ZJ., Cheang, L.C.V., Wang, MW. et al. Ethanolic Extract of Fructus Alpinia oxyphylla Protects Against 6-Hydroxydopamine-Induced Damage of PC12 Cells In Vitro and Dopaminergic Neurons in Zebrafish. Cell Mol Neurobiol 32, 27–40 (2012). https://doi.org/10.1007/s10571-011-9731-0

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  • DOI: https://doi.org/10.1007/s10571-011-9731-0

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