Neuroprotective and Anti-Inflammatory Effects of Evernic Acid in an MPTP-Induced Parkinson's Disease Model

Int J Mol Sci. 2021 Feb 20;22(4):2098. doi: 10.3390/ijms22042098.

Abstract

Oxidative stress, mitochondrial dysfunction, and neuroinflammation are strongly associated with the pathogenesis of Parkinson's disease (PD), which suggests that anti-oxidative and anti-inflammatory compounds might provide an alternative treatment for PD. Here, we evaluated the neuroprotective effects of evernic aid (EA), which was screened from a lichen library provided by the Korean Lichen Research Institute at Sunchon National University. EA is a secondary metabolite generated by lichens, including Ramalina, Evernia, and Hypogymnia, and several studies have described its anticancer, antifungal, and antimicrobial effects. However, the neuroprotective effects of EA have not been studied. We found that EA protected primary cultured neurons against 1-methyl-4-phenylpyridium (MPP+)-induced cell death, mitochondrial dysfunction, and oxidative stress, and effectively reduced MPP+-induced astroglial activation by inhibiting the NF-κB pathway. In vivo, EA ameliorated MPTP-induced motor dysfunction, dopaminergic neuronal loss, and neuroinflammation in the nigrostriatal pathway in C57BL/6 mice. Taken together, our findings demonstrate that EA has neuroprotective and anti-inflammatory effects in PD models and suggest that EA is a potential therapeutic candidate for PD.

Keywords: 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Parkinson’s disease; anti-inflammation; evernic acid; neuroinflammation; neuroprotection.

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Apoptosis / drug effects
  • Astrocytes / drug effects
  • Astrocytes / metabolism
  • Astrocytes / pathology
  • Cells, Cultured
  • Disease Models, Animal
  • Dopaminergic Neurons / drug effects
  • Dopaminergic Neurons / metabolism
  • Dopaminergic Neurons / pathology
  • Drug Evaluation, Preclinical
  • Hydroxybenzoates / chemistry
  • Hydroxybenzoates / pharmacology
  • Hydroxybenzoates / therapeutic use*
  • Lichens / chemistry
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Motor Activity / drug effects
  • NF-kappa B / metabolism
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use*
  • Oxidative Stress / drug effects
  • Parkinson Disease / drug therapy*
  • Parkinson Disease / pathology
  • Parkinson Disease / physiopathology
  • Signal Transduction / drug effects

Substances

  • Anti-Inflammatory Agents
  • Hydroxybenzoates
  • NF-kappa B
  • Neuroprotective Agents
  • evernic acid
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine