Neuroprotective Effects and Related Mechanisms of Echinacoside in MPTP-Induced PD Mice

Zhen-Nian Zhang; Zhen Hui; Chang Chen; Yan Liang; Li-Li Tang; Su-Lei Wang; Cheng-Cheng Xu; Hui Yang; Jing-Si Zhang; Yang Zhao

doi:10.2147/NDT.S299685

Neuroprotective Effects and Related Mechanisms of Echinacoside in MPTP-Induced PD Mice

Neuropsychiatr Dis Treat. 2021 Jun 3:17:1779-1792. doi: 10.2147/NDT.S299685. eCollection 2021.

Authors

Zhen-Nian Zhang^#¹, Zhen Hui^#¹, Chang Chen¹, Yan Liang¹, Li-Li Tang¹, Su-Lei Wang¹, Cheng-Cheng Xu¹, Hui Yang¹, Jing-Si Zhang², Yang Zhao¹

Affiliations

¹ Department of Neurology, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, 210022, People's Republic of China.
² Department of Neurology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People's Republic of China.

^# Contributed equally.

Abstract

Objective: To explore the neuroprotective effect and the related mechanisms of echinacoside (ECH) in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) mice.

Methods: Parkinson's disease is induced in mice by MPTP and the neurobehaviors of mice in different groups are observed. Then, immunohistochemistry and Western blot analysis are adopted to measure the expression of tyrosine hydroxylase (TH) and α-synuclein in the substantia nigra (SN). The content of dopamine (DA) and other neurotransmitters in the brain is detected by high-performance liquid chromatography. The expression of nerve growth factors and inflammatory factors in SN in mice in each group is measured by quantitative polymerase chain reaction. Finally, the expression of oxidative stress-related parameters in each group is measured.

Results: Compared with the model group, the pole-climbing time among mice in the moderate and high-dose ECH groups is significantly reduced (P < 0.01). The rotarod staying time, as well as fore and hind-limb strides, shows a significant increase (P < 0.01), as does spontaneous activity (P < 0.01). Moreover, the expression levels of TH, DA, glial cell line-derived neurotrophic factor, and brain-derived neurotrophic factor in SN in mice show significant increases in these two groups (P < 0.01). The content of superoxide dismutase, catalase, and glutathione peroxidase indicates significant increases in the low, moderate, and high-dose ECH groups (P < 0.01), and the content of MDA was reduced (P < 0.01). In the high-dose ECH group, the expression of interleukin (IL) 6 and tumor necrosis factor-α is significantly reduced (P < 0.01), while the expression of IL-10 shows a marked increase (P < 0.01) alongside a decrease in the expression of α-synuclein (P < 0.01).

Conclusion: Echinacoside improves neurobehavioral symptoms in PD mice and significantly increases the expression of TH and DA. The neuroprotective effect potentially correlates with anti-inflammation and anti-oxidation actions, promotes the expression of nerve growth factor, and reduces the accumulation of α-synuclein.

Keywords: BDNF; GDNF; IL-10; IL-6; MPTP; Parkinson’s disease; TNF-α; echinacoside; neuroprotection; oxidative stress; α-synuclein.

Grants and funding

This study was funded by:Nanjing Health Science and Technology Development Special Fund Grant (YKK18134);Jiangsu Provincial Bureau of Traditional Chinese Medicine “Chinese Medicine Brain Diseases” Key Discipline Cultivation Project (NBPY201704);Nanjing University of Chinese Medicine “Jiangsu University Nursing Advantageous Discipline Construction Project Funding Project” (2019YSHL098);Nanjing “Thirteenth Five-Year Plan” Famous Chinese Medicine Doctor (Kong-Jiang Liu) Studio Construction Project (LKJ-2017-NJ);Nanjing “Thirteenth Five-Year Plan” Famous Chinese Medicine Doctor (Jing-Qing Wang) Studio Construction Project (WJQ-2019-NJ).The funding body had no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript.