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Neurochemical Research

, Volume 42, Issue 4, pp 975–985 | Cite as

Neuroprotective Effects of Echinacoside on Regulating the Stress-Active p38MAPK and NF-κB p52 Signals in the Mice Model of Parkinson’s Disease

  • Jingsi Zhang
  • Zhennian Zhang
  • Jun Xiang
  • Min Cai
  • Zhonghai Yu
  • Xiangting Li
  • Ting Wu
  • Dingfang Cai
Original Paper

Abstract

Herbal medicines have long been used to treat Parkinson’s disease (PD). To systematically analyze the anti-parkinsonian activity of echinacoside (ECH) in a neurotoxic model of PD and provide a future basis for basic and clinical investigations, male C57BL/6 mice were randomized into blank control, PD model and ECH-administration groups. ECH significantly suppressed the dopaminergic neuron loss (P < 0.01) caused by MPTP and maintained dopamine content (P < 0.01) and dopamine metabolite content (P < 0.05) compared with that measured in mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced damage. Additionally, ECH inhibited the activation of microglia and astrocytes in the substantia nigra, which suggested the involvement of neuroinflammation. The relevant cytokines were detected with a Proteome Profiler Array, which confirmed that ECH participated in the regulation of seven cytokines. Given that p38 mitogen-activated protein kinase (p38MAPK) and NF-kappaB (NF-κB) signals are considered to be closely related to neuroninflammation, the gene expression levels of p38MAPK and six NF-κB DNA-binding subunits were assessed. Western blotting analysis showed that both p38MAPK and the NF-κB p52 subunit were upregulated in the MPTP group and that ECH downregulated their expressions. Minocycline was administered as the positive control to inhibit neuroinflammation, and no differences were detected between the minocycline- and ECH-mediated inhibition of the p38MAPK and NF-κB p52 signals. In conclusion, echinacoside is a potential novel orally active compound for regulating neuroinflammation and related signals in Parkinson’s disease and may provide a new prospect for clinical treatment.

Keywords

Neuroprotective Neuroinflammation Echinacoside Microglia Cytokines 

Abbreviations

PD

Parkinson’s disease

SNpc

Substantia nigra pars compacts

MPTP

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine

ECH

Echinacoside

PhGs

Phenylethanoid glycosides

TH

Tyrosine hydroxylase

GDNF

Glial cell line-derived neurotrophic factor

BDNF

Brain-derived neurotrophic factor

HPLC

High-performance liquid chromatography

Iba1

Ionized calcium binding adapter molecule 1

GFAP

Glial fibrillary acidic protein

Notes

Acknowledgements

The work was supported by Grants from the National Natural Science Foundation of China (Grant Number: 81373866), the 3-year development plan project for Traditional Chinese Medicine (major research) of the Shanghai municipal health bureau (Grant Number: ZYSNXD-CC-ZDYJ028), and the 3-year development plan project for Traditional Chinese Medicine (Grant Number: ZY3-CCCX-3-7003, ZY3-CCCX-1-1015).

Compliance with Ethical Standards

Conflict of interest

The authors report no conflicts of interest in this work.

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Department of Integrative Medicine, Zhongshan HospitalFudan UniversityShanghaiChina

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