Wuzi Yanzong Pill Plays A Neuroprotective Role in Parkinson's Disease Mice via Regulating Unfolded Protein Response Mediated by Endoplasmic Reticulum Stress

LI Yan-rong; FAN Hui-jie; SUN Rui-rui; JIA Lu; YANG Li-yang; ZHANG Hai-fei; JIN Xiao-ming; XIAO Bao-guo; MA Cun-gen; CHAI Zhi

doi:10.1007/s11655-022-3727-0

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Wuzi Yanzong Pill Plays A Neuroprotective Role in Parkinson's Disease Mice via Regulating Unfolded Protein Response Mediated by Endoplasmic Reticulum Stress

Original Article | Updated：2023-01-05

- Wuzi Yanzong Pill Plays A Neuroprotective Role in Parkinson's Disease Mice via Regulating Unfolded Protein Response Mediated by Endoplasmic Reticulum Stress
- Wuzi Yanzong Pill Plays A Neuroprotective Role in Parkinson's Disease Mice via Regulating Unfolded Protein Response Mediated by Endoplasmic Reticulum Stress
- 中国结合医学杂志（英文版） 2023年29卷第1期页码：19-27
- Affiliations：
  
  1.The Key Research Laboratory of Benefiting Qi for Acting Blood Circulation Method to Treat Multiple Sclerosis of State Administration of Traditional Chinese Medicine, Shanxi University of Chinese Medicine, Jinzhong, Shanxi Province (030619), China
  2.Institute of Brain Science Department, Neurology of First Affiliated Hospital, Shanxi Datong University, Datong, Shanxi Province (037009), China
  3.Department of Anatomy and Cell Biology, Department of Neurological Surgery, Spinal Cord and Brain Injury Research Group, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis(IN 46202), USA
  4.Institute of Neurology, Huashan Hospital,Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai (200025), China
- Author bio：
  
  Prof. CHAI Zhi, E-mail: chaizhi@sxtcm.edu.cn
- Funds：
  
  the National Natural Science Foundation of China(81703978;81102552);the Special Fund for Science and Technology Innovation Team of Shanxi University of Chinese Medicine(2022TD1013);the Natural Science Foundation of Shanxi Province(201901D111334);the Returned Chinese Scholars Technology Activities Preferred Project, Shanxi Province of China(20200026);the Research Project supported by Shanxi Scholarship Council of China(2021-142);Shanxi University Science and Technology Innovation Project(2019L0724);the Key Science and technology R&D project of Jinzhong(Y213004);the Young Scientist Cultivation Program Project, Shanxi University of Chinese Medicine(2021PY-QN-03)
- DOI：10.1007/s11655-022-3727-0
  中图分类号：
- 纸质出版日期：2023-01-01，
  
  网络出版日期：2022-11-12，
  
  录用日期：2022-06-29
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Wuzi Yanzong Pill Plays A Neuroprotective Role in Parkinson's Disease Mice via Regulating Unfolded Protein Response Mediated by Endoplasmic Reticulum Stress[J]. 中国结合医学杂志（英文版）, 2023,29(1):19-27.

LI Yan-rong, FAN Hui-jie, SUN Rui-rui, et al. Wuzi Yanzong Pill Plays A Neuroprotective Role in Parkinson's Disease Mice via Regulating Unfolded Protein Response Mediated by Endoplasmic Reticulum Stress[J]. Chinese Journal of Integrative Medicine, 2023,29(1):19-27.
Wuzi Yanzong Pill Plays A Neuroprotective Role in Parkinson's Disease Mice via Regulating Unfolded Protein Response Mediated by Endoplasmic Reticulum Stress[J]. 中国结合医学杂志（英文版）, 2023,29(1):19-27. DOI： 10.1007/s11655-022-3727-0.

LI Yan-rong, FAN Hui-jie, SUN Rui-rui, et al. Wuzi Yanzong Pill Plays A Neuroprotective Role in Parkinson's Disease Mice via Regulating Unfolded Protein Response Mediated by Endoplasmic Reticulum Stress[J]. Chinese Journal of Integrative Medicine, 2023,29(1):19-27. DOI： 10.1007/s11655-022-3727-0.

摘要

Abstract

Objective:

To investigate the protective effects and its possible mechanism of Wuzi Yanzong Pill (WYP) on Parkinson's disease (PD) model mice.

Methods:

Thirty-six C57BL/6 male mice were randomly assigned to 3 groups including normal

and PD+WYP groups

12 mice in each group. One week of intraperitoneal injection of 1-methyl-4-phenyl-1

6-tetrahydropyridine (MPTP) was used to establish the classical PD model in mice. Meanwhile

mice in the PD+WYP group were administrated with 16 g/kg WYP

twice daily by gavage. After 14 days of administration

gait test

open field test and pole test were measured to evaluate the movement function. Tyrosine hydroxylase (TH) neurons in substantia nigra of midbrain and binding immunoglobulin heavy chain protein (GRP78) in striatum and cortex were observed by immunohistochemistry. The levels of TH

GRP78

p-PERK

p-eIF2α

ATF4

p-IRE1α

XBP1

ATF6

CHOP

ASK1

p-JNK

Caspase-12

-9 and -3 in brain were detected by Western blot.

Results:

Compared with the PD group

WYP treatment ameliorated gait balance ability in PD mice (

0.05). Similarly

WYP increased the total distance and average speed (

0.05 or

0.01)

reduced rest time and pole time (

0.05). Moreover

WYP significantly increased TH positive cells (

0.01). Immunofluorescence showed WYP attenuated the levels of GRP78 in striatum and cortex. Meanwhile

WYP treatment significantly decreased the protein expressions of GRP78

p-PERK

p-eIF2α

ATF4

p-IRE1α

XBP1

CHOP

Caspase-12 and Caspase-9 (

0.05 or

0.01).

Conclusions:

WYP ameliorated motor symptoms and pathological lesion of PD mice

which may be related to the regulation of unfolded protein response-mediated signaling pathway and inhibiting the endoplasmic reticulum stress-mediated neuronal apoptosis pathway.

关键词

Keywords

Wuzi Yanzong PillParkinson's diseasedopaminergic neuronsendoplasmic reticulum stressapoptosis

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