Silibinin Attenuates Motor Dysfunction in a Mouse Model of Parkinson's Disease by Suppression of Oxidative Stress and Neuroinflammation along with Promotion of Mitophagy

Neuroinflammation is the neuropathological feature of Parkinson’s disease (PD) and causes microglial activation and activated microglia-derived oxidative stress in the PD patients and PD animal models, resulting in neurodegeneration. The present study examined whether norfluoxetine (a metabolite of fluoxetine) could regulate neuroinflammation in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropypridine (MPTP) mouse model of PD and rescue dopamine neurons. Analysis by tyrosine hydroxylase (TH) immunohistochemistry demonstrated that norfluoxetine prevents degeneration of nigrostriatal dopamine neurons in vivo in MPTP-lesioned mice compared to vehicle-treated MPTP-lesioned control mice. MAC-1 immunostaining and hydroethidine histochemical staining showed that norfluoxetine neuroprotection is accompanied by inhibiting MPTP-induced microglial activation and activated microglia-derived reactive oxygen species production in vivo, respectively. In the separate experiments, treatment with norfluoxetine inhibited NADPH oxidase activation and nitrate production in LPS-treated cortical microglial cultures in vitro. Collectively, these in vivo and in vitro results suggest that norfluoxetine could be employed as a novel therapeutic agent for treating PD, which is associated with neuroinflammation and microglia-derived oxidative stress.

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Neuro-protective effects of Ligustri Fructus by suppression of oxidative stress in mouse model of Parkinson’s disease

Oriental Pharmacy and Experimental Medicine ◽

10.1007/s13596-016-0223-0 ◽

2016 ◽

Vol 16 (2) ◽

pp. 123-129 ◽

Cited By ~ 1

Author(s):

Minsook Ye ◽

Minhwan Kim ◽

Hyunsu Bae

Keyword(s):

Oxidative Stress ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Mouse Model ◽

Protective Effects

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Deletion ofHerpud1Enhances Heme Oxygenase-1 Expression in a Mouse Model of Parkinson’s Disease

Parkinson s Disease ◽

10.1155/2016/6163934 ◽

2016 ◽

Vol 2016 ◽

pp. 1-9 ◽

Cited By ~ 1

Author(s):

Thuong Manh Le ◽

Koji Hashida ◽

Hieu Minh Ta ◽

Mika Takarada-Iemata ◽

Koichi Kokame ◽

...

Keyword(s):

Oxidative Stress ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Mouse Model ◽

Heme Oxygenase ◽

Active Form ◽

Heme Oxygenase 1 ◽

Protein Levels ◽

The Status ◽

Mptp Administration

Herp is an endoplasmic reticulum- (ER-) resident membrane protein that plays a role in ER-associated degradation. We studied the expression of Herp and its effect on neurodegeneration in a mouse model of Parkinson’s disease (PD), in which both the oxidative stress and the ER stress are evoked. Eight hours after administering a PD-related neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), to mice, the expression of Herp increased at both the mRNA and the protein levels. Experiments usingHerpud1+/+andHerpud1−/−mice revealed that the status of acute degeneration of nigrostriatal neurons and reactive astrogliosis was comparable between two genotypes after MPTP injection. However, the expression of a potent antioxidant, heme oxygenase-1 (HO-1), was detected to a higher degree in the astrocytes ofHerpud1−/−mice than in the astrocytes ofHerpud1+/+mice 24 h after MPTP administration. Further experiments using cultured astrocytes revealed that the stress response against MPP+, an active form of MPTP, and hydrogen peroxide, both of which cause oxidative stress, was comparable between the two genotypes. These results suggest that deletion ofHerpud1may cause a slightly higher level of initial damage in the nigrastrial neurons after MPTP administration but is compensated for by higher induction of antioxidants such as HO-1 in astrocytes.

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

International Journal of Molecular Sciences ◽

10.3390/ijms22042098 ◽

2021 ◽

Vol 22 (4) ◽

pp. 2098

Author(s):

Seulah Lee ◽

Yeon Ji Suh ◽

Seonguk Yang ◽

Dong Geun Hong ◽

Akihito Ishigami ◽

...

Keyword(s):

Oxidative Stress ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Mitochondrial Dysfunction ◽

Neuronal Loss ◽

Motor Dysfunction ◽

Nigrostriatal Pathway ◽

Neuroprotective Effects ◽

Anti Inflammatory

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.

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