Neuroscience Bulletin

, Volume 32, Issue 4, pp 349–362 | Cite as

Echinacoside Protects Against MPP+-Induced Neuronal Apoptosis via ROS/ATF3/CHOP Pathway Regulation

  • Qing Zhao
  • Xiaoyan Yang
  • Dingfang Cai
  • Ling Ye
  • Yuqing Hou
  • Lijun Zhang
  • Jiwei Cheng
  • Yuan Shen
  • Kaizhe Wang
  • Yu Bai
Original Article


Echinacoside (ECH) is protective in a mouse model of Parkinson’s disease (PD) induced by 1-methyl-4-phenylpyridinium ion (MPP+). To investigate the mechanisms involved, SH-SY5Y neuroblastoma cells were treated with MPP+ or a combination of MPP+ and ECH, and the expression of ATF3 (activating transcription factor 3), CHOP (C/EBP-homologous protein), SCNA (synuclein alpha), and GDNF (glial cell line-derived neurotrophic factor) was assessed. The results showed that ECH significantly improved cell survival by inhibiting the generation of MPP+-induced reactive oxygen species (ROS). In addition, ECH suppressed the ROS and MPP+-induced expression of apoptotic genes (ATF3, CHOP, and SCNA). ECH markedly decreased the MPP+-induced caspase-3 activity in a dose-dependent manner. ATF3-knockdown also decreased the CHOP and cleaved caspase-3 levels and inhibited the apoptosis induced by MPP+. Interestingly, ECH partially restored the GDNF expression that was down-regulated by MPP+. ECH also improved dopaminergic neuron survival during MPP+ treatment and protected these neurons against the apoptosis induced by MPTP. Taken together, these data suggest that the ROS/ATF3/CHOP pathway plays a critical role in mechanisms by which ECH protects against MPP+-induced apoptosis in PD.


Echinacoside Parkinson’s disease 1-Methyl-4-phenylpyridinium ion Reactive oxygen species ATF3 CHOP 



This work was supported by the National Natural Science Foundation of China (81202814), the Shanghai Municipal Commission of Health and Family Planning (20124y116) and the Young Teachers Training Funding Scheme of Shanghai Colleges and Universities, China (zzszy12026). We thank Dr. Yunsheng Yuan, Professor Dazheng Wu, and Associate Professor Peihao Yin for their guidance on the experiments and preparation of the manuscript.

Supplementary material

12264_2016_47_MOESM1_ESM.pdf (209 kb)
Supplementary material 1 (PDF 208 kb)


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Copyright information

© Shanghai Institutes for Biological Sciences, CAS and Springer Science+Business Media Singapore 2016

Authors and Affiliations

  • Qing Zhao
    • 1
  • Xiaoyan Yang
    • 2
  • Dingfang Cai
    • 3
    • 4
  • Ling Ye
    • 5
    • 6
  • Yuqing Hou
    • 1
  • Lijun Zhang
    • 1
  • Jiwei Cheng
    • 1
  • Yuan Shen
    • 1
  • Kaizhe Wang
    • 5
  • Yu Bai
    • 1
  1. 1.Department of Neurology, Putuo HospitalShanghai University of Traditional Chinese MedicineShanghaiChina
  2. 2.Department of Emergency Internal Medicine, Putuo HospitalShanghai University of Traditional Chinese MedicineShanghaiChina
  3. 3.Laboratory of Neurology, Institute of Integrative Medicine, Zhongshan HospitalFudan UniversityShanghaiChina
  4. 4.Department of Integrative Medicine, Zhongshan HospitalFudan UniversityShanghaiChina
  5. 5.Center for Translational Neurodegeneration and Regenerative TherapyShanghai Tenth People’s Hospital Affiliated with Tongji University School of MedicineShanghaiChina
  6. 6.Department of ImmunologyTongji University School of MedicineShanghaiChina

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