Neuroprotective Effect of Echinacoside in Subacute Mouse Model of Parkinson's Disease

Biomed Res Int. 2019 Jan 30:2019:4379639. doi: 10.1155/2019/4379639. eCollection 2019.


Objective: To study the protective effect of Echinacoside for 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced dopaminergic (DA) neurons injury in the subacute mouse model of Parkinson's disease (PD) and to explore its mechanism of action.

Methods: We chose 10 weeks of healthy wild type C57BL/6 male mice, hypodermic MPTP 30 mg/kg/day, five days, to prepare PD subacute mouse model. Behavior indexes of open field test and pole test were applied to examine the function of ECH to PD subacute mice model of PD sample action. The effects of ECH on dopaminergic neurons and astrocyte were examined using Immunohistochemistry including tyrosine hydroxylase (TH) and glial fibrillary acidic protein (GFAP) expression. The total numbers of TH-positive neurons and GFAP-positive cells in the substantia nigra pars compacts (SNpc) and ventral tegmental area (VTA) were obtained stereologically using the optical fractionator method. Enzyme-linked immunosorbent assay (ELISA) method was used to detect the inflammatory cytokines in the serum, including TNF-α (Ttumor necrosis factor alpha) and IFN-γ (interferon gamma). Protein expressions of ionized calcium binding adaptor molecule 1 (IBA-1), TNF-α, Cleaved caspase-3, glial derived neurotrophic factor (GDNF), and phosphorylated and total extracellular signal-regulated kinase (p-ERK and ERK) in the anatomical region of substantia nigra (SN) were tested by protein immunoblot method (i.e., Western blotting).

Results: ECH reversed the reduction of total distance in open field test in MPTP-induced PD model mice (P < 0.01), shortened the return time and total time of PD subacute model mice in pole test (P < 0.01, P < 0.05), significantly reversed the reduction of TH positive neurons induced by MPTP (P < 0.05), and reduced the activation of astrocytes (P < 0.05). Meanwhile, ECH significantly inhibited the expression of IBA-1, Cleaved caspase-3, and TNF-α in midbrain of MPTP model mice (P < 0.05, P < 0.05, and P < 0.05) and upregulated the expression of GDNF (P < 0.05). And ECH lowered the level of TNF-α and IFN-γ in serum (P < 0.05, P < 0.05).

Conclusion: ECH has protective effects on the MPTP subacute model mice, its mechanism may be through inhibiting activation of microglia and astrocytes, reducing inflammatory reaction and promoting the secretion of neurotrophic factors, and eventually resulting in the reduction of the DA neurons apoptosis.

MeSH terms

  • Animals
  • Calcium-Binding Proteins / genetics
  • Caspase 3 / genetics
  • Corpus Striatum / drug effects
  • Corpus Striatum / pathology
  • Disease Models, Animal
  • Dopaminergic Neurons / drug effects
  • Dopaminergic Neurons / pathology
  • Gene Expression Regulation / drug effects
  • Glial Fibrillary Acidic Protein / genetics
  • Glycosides / administration & dosage*
  • Humans
  • Immunohistochemistry
  • MPTP Poisoning / drug therapy*
  • MPTP Poisoning / genetics
  • MPTP Poisoning / pathology
  • Mice
  • Microfilament Proteins / genetics
  • Microglia / drug effects
  • Microglia / pathology
  • Neuroprotective Agents / administration & dosage*
  • Parkinson Disease / drug therapy*
  • Parkinson Disease / genetics
  • Parkinson Disease / pathology
  • Substantia Nigra / drug effects
  • Substantia Nigra / pathology
  • Tumor Necrosis Factor-alpha / genetics
  • Tyrosine 3-Monooxygenase / genetics


  • Aif1 protein, mouse
  • Calcium-Binding Proteins
  • Glial Fibrillary Acidic Protein
  • Glycosides
  • Microfilament Proteins
  • Neuroprotective Agents
  • Tumor Necrosis Factor-alpha
  • glial fibrillary astrocytic protein, mouse
  • Tyrosine 3-Monooxygenase
  • Casp3 protein, mouse
  • Caspase 3
  • echinacoside