NeuroMolecular Medicine

, Volume 19, Issue 4, pp 480–492 | Cite as

Isorhynchophylline Attenuates MPP+-Induced Apoptosis Through Endoplasmic Reticulum Stress- and Mitochondria-Dependent Pathways in PC12 Cells: Involvement of Antioxidant Activity

  • Xiao-Ming Li
  • Xiao-Jie Zhang
  • Miao-Xian DongEmail author
Original Paper


Endoplasmic reticulum stress (ERS) and mitochondrial dysfunctions are thought to be involved in the dopaminergic neuronal death in Parkinson’s disease (PD). In this study, we found that isorhynchophylline (IRN) significantly attenuated 1-methyl-4-phenylpyridinium (MPP+)-induced apoptotic cell death and oxidative stress in PC12 cells. IRN markedly reduced MPP+-induced-ERS responses, indicative of inositol-requiring enzyme 1 (IRE1) phosphorylation and caspase-12 activation. Furthermore, IRN inhibits MPP+-triggered apoptosis signal-regulating kinase 1 (ASK1)/c-Jun N-terminal Kinase (JNK) signaling-mediated mitochondria-dependent apoptosis pathway. IRN-mediated attenuation of endoplasmic reticulum modulator caspase-12 activation was abolished by diphenyleneiodonium (DPI) or IRE-1α shRNA, but not by SP600125 or pifithrin-α in MPP+-treated PC12 cells. Inhibitions of MPP+-induced both cytochrome c release and caspase-9 activation by IRN were blocked by pre-treatment with DPI or pifithrin-α, but not by IRE-1α shRNA. IRN blocks the generation of reactive oxygen species upstream of both ASK1/JNK pathway and IRE1/caspase-12 pathway. Altogether, our in vitro findings suggest that IRN possesses potent neuroprotective activity and may be a potential candidate for the treatment of PD.


Isorhynchophylline Parkinson’s disease Apoptosis Mitochondria dysfunction Endoplasmic reticulum stress 



This study was funded by the National Natural Science Foundation of China grant (Grant Number 81373629) awarded to Miao-Xian Dong. We thank Zhi Pan for valuable scientific discussion.

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  1. 1.The Institute of MedicineQiqihar Medical UniversityQiqiharChina

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