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

NEUROPSYCHIATRIC DISEASE AND TREATMENT(2021)

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摘要
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 alpha-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-alpha 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 alpha-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 alpha-synuclein.
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关键词
Parkinson's disease,MPTP,echinacoside,alpha-synuclein,oxidative stress,neuroprotection,BDNF,GDNF,IL-6,TNF-alpha,IL-10
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