Central and Enteric Neuroprotective Effects by Eucommia ulmoides Extracts on Neurodegeneration in Rotenone-induced Parkinsonian Mouse

Acta Med Okayama. 2022 Aug;76(4):373-383. doi: 10.18926/AMO/63889.

Abstract

Parkinson's disease (PD) is a progressive neurodegenerative disease of both the central and peripheral / enteric nervous systems. Oxidative stress and neuroinflammation are associated with the pathogenesis of PD, suggesting that anti-oxidative and anti-inflammatory compounds could be neuroprotective agents for PD. Eucommia ulmoides (EU) is a traditional herbal medicine which exerts neuroprotective effects by anti-inflammatory and anti-oxidative properties. Our previous study showed that treatment with chlorogenic acid, a component of EU, protected against neurodegeneration in the central and enteric nervous systems in a PD model. In this study, we examined the effects of EU extract (EUE) administration on dopaminergic neurodegeneration, glial response and α-synuclein expression in the substantia nigra pars compacta (SNpc), and intestinal enteric neurodegeneration in low-dose rotenone-induced PD model mice. Daily oral administration of EUE ameliorated dopaminergic neurodegeneration and α-synuclein accumulation in the SNpc. EUE treatment inhibited rotenone-induced decreases in the number of total astrocytes and in those expressing the antioxidant molecule metallothionein. EUE also prevented rotenone-induced microglial activation. Furthermore, EUE treatment exerted protective effects against intestinal neuronal loss in the PD model. These results suggest that EU exerts neuroprotective effects in the central and enteric nervous systems of rotenone-induced parkinsonism mice, in part by glial modification.

Keywords: Eucommia ulmoides; Parkinson’s disease; dopamine neuron; enteric neuron; glia.

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Chlorogenic Acid / metabolism
  • Chlorogenic Acid / pharmacology
  • Dopamine / metabolism
  • Dopamine / pharmacology
  • Dopaminergic Neurons / metabolism
  • Dopaminergic Neurons / pathology
  • Eucommiaceae* / metabolism
  • Metallothionein / metabolism
  • Metallothionein / pharmacology
  • Mice
  • Neurodegenerative Diseases* / metabolism
  • Neurodegenerative Diseases* / pathology
  • Neuroprotective Agents* / metabolism
  • Neuroprotective Agents* / pharmacology
  • Neuroprotective Agents* / therapeutic use
  • Plant Extracts / metabolism
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use
  • Rotenone / metabolism
  • Rotenone / pharmacology
  • alpha-Synuclein / metabolism
  • alpha-Synuclein / pharmacology

Substances

  • Antioxidants
  • Neuroprotective Agents
  • Plant Extracts
  • alpha-Synuclein
  • Rotenone
  • Chlorogenic Acid
  • Metallothionein
  • Dopamine