1. Academic Validation
  2. Eupatilin prevents behavioral deficits and dopaminergic neuron degeneration in a Parkinson's disease mouse model

Eupatilin prevents behavioral deficits and dopaminergic neuron degeneration in a Parkinson's disease mouse model

  • Life Sci. 2020 Jul 15;253:117745. doi: 10.1016/j.lfs.2020.117745.
Yuan Zhang 1 Lina Qin 2 Jieru Xie 1 Juan Li 1 Chong Wang 3
Affiliations

Affiliations

  • 1 Department of Basic Medical Sciences, School of Medicine, Xiamen University, Xiamen, Fujian 361102, PR China.
  • 2 Department of Histology and Embryology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong 510080, PR China.
  • 3 Department of Basic Medical Sciences, School of Medicine, Xiamen University, Xiamen, Fujian 361102, PR China. Electronic address: wangchong@xmu.edu.cn.
Abstract

Aims: Neuroinflammation and Apoptosis play a crucial role in Parkinson's disease (PD) pathogenesis. Eupatilin is a lipophilic flavonoid isolated from Artemisia species and exerts anti-apoptotic and anti-inflammatory activities. In this study, we investigated the effects of Eupatilin on a mouse model of PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).

Main methods: The rotarod test and traction test were constructed to examine the motor function. Immunofluorescent staining was performed to detect the expression of TH, Iba-1 and GFAP. Apoptosis was examined by the TUNEL assay. Real-Time PCR was used to determine the mRNA expression and Western blot and ELISA were used to determine the protein expression.

Key findings: Eupatilin improved behavioral impairment caused by MPTP. A loss of TH positive neurons was observed in the substantia nigra pars compacta of MPTP-lesioned brain, while it was rescued by Eupatilin. Moreover, MPTP administration increased the cell number of microglia and astrocytes and the expression of inflammatory factors TNF-α, IL-1β, and IL-6. Whereas Eupatilin suppressed the activation of neuroinflammation. Eupatilin also decreased cell Apoptosis enhanced by MPTP/MPP+ exposure in vivo and in vitro. We further revealed that Eupatilin abolished MPTP-induced downregulation of IκBα expression and accumulation of p65 in the nuclear compartment. Besides, MPTP administration led to dephosphorylation of Akt and GSK-3β, but it was restored by Eupatilin.

Significance: We demonstrate that Eupatilin alleviates behavioral impairment and dopaminergic neuron loss induced by MPTP through inhibition of neuroinflammation and Apoptosis. Our research provides more evidence for Eupatilin as a potential preventative drug for PD.

Keywords

Apoptosis; Eupatilin; Neuroinflammation; Parkinson's disease.

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