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

Yeon Ji Suh,Jaewon Lee,Seung-Cheol Chang,Hangun Kim,Jae-Seoun Hur,Dong Geun Hong,Seonguk Yang,Seulah Lee,Akihito Ishigami

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.

Highlights

Parkinson’s disease (PD) is a common movement disorder characterized by bradykinesia, rigidity, and slow movements accompanied by nonmotor symptoms such as anxiety, sleep disorder, and dementia
The lichen extract library was provided by the Korean Lichen Research Institute (KoLRI) in Sunchon National University (Suncheon, Korea) and neuroprotective effects were screened using primary cultured neurons
Animal models, and postmortem brain tissues indicate dopaminergic neuron apoptosis is a characteristic of PD [27,28,29]

Summary

Introduction

Parkinson’s disease (PD) is a common movement disorder characterized by bradykinesia, rigidity, and slow movements accompanied by nonmotor symptoms such as anxiety, sleep disorder, and dementia. The neurodegenerative features of PD include dopaminergic neuronal loss in the substantia nigra (SN), accumulation of α-synuclein, and chronic neuroinflammation [1]. While present clinical treatments aim to recover dopamine levels or inhibit endogenous dopamine degradation, it was recently suggested treatment strategies might be directed toward removing direct causes of neurodegeneration by suppressing chronic neuroinflammation [2,3]. Several studies have presented evidence that activated microglia and reactive astrocytes induce neurodegeneration [4,5], which suggests anti-inflammatory agents offer a potential means of targeting PD. The metabolites produced by lichens exhibit antioxidant, antimicrobial, anticancer, antiviral, and anti-inflammatory effects [9,10,11,12,13]

Methods

Results

Conclusion