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.

Parkinson’s disease (PD) is a progressive movement disorder caused by nigrostriatal neurodegeneration. Since chronically activated neuroinflammation accelerates neurodegeneration in PD, we considered that modulating chronic neuroinflammatory response might provide a novel therapeutic approach. Glycogen synthase kinase 3 (GSK-3) is a multifunctional serine/threonine protein kinase with two isoforms, GSK-3α and GSK-3β, and GSK-3β plays crucial roles in inflammatory response, which include microglial migration and peripheral immune cell activation. GSK-3β inhibitory peptide (IAGIP) is specifically activated by activated inhibitory kappa B kinase (IKK), and its therapeutic effects have been demonstrated in a mouse model of colitis. Here, we investigated whether the anti-inflammatory effects of IAGIP prevent neurodegeneration in the rodent model of PD. IAGIP significantly reduced MPP⁺-induced astrocyte activation and inflammatory response in primary astrocytes without affecting the phosphorylations of ERK or JNK. In addition, IAGIP inhibited LPS-induced cell migration and p65 activation in BV-2 microglial cells. In vivo study using an MPTP-induced mouse model of PD revealed that intravenous IAGIP effectively prevented motor dysfunction and nigrostriatal neurodegeneration. Our findings suggest that IAGIP has a curative potential in PD models and could offer new therapeutic possibilities for targeting PD.

Neurodegenerative diseases such as Parkinson’s disease (PD) are known to be related to oxidative stress and neuroinflammation, and thus, modulating neuroinflammation offers a possible means of treating PD-associated pathologies. Morin (2′,3,4′,5,7-pentahydroxy flavone) is a flavonol with anti-oxidative and anti-inflammatory effects found in wines, herbs, and fruits. The present study was undertaken to determine whether a morin-containing diet has protective effects in an MPTP-induced mouse model of PD. Mice were fed a control or morin diet for 34 days, and then MPTP (30 mg/kg, i.p.) was administered daily for 5 days to induce a PD-like pathology. We found that dietary morin prevented MPTP-induced motor dysfunction and ameliorated dopaminergic neuronal damage in striatum (STR) and substantia nigra (SN) in our mouse model. Furthermore, MPTP-induced neuroinflammation was significantly reduced in mice fed morin. In vitro studies showed that morin effectively suppressed glial activations in primary microglia and astrocytes, and biochemical analysis and a docking simulation indicated that the anti-inflammatory effects of morin were mediated by blocking the extracellular signal-regulated kinase (ERK)-p65 pathway. These findings suggest that morin effectively inhibits glial activations and has potential use as a functional food ingredient with therapeutic potential for the treatment of PD and other neurodegenerative diseases associated with neuroinflammation.

Parkinson’s disease (PD) is one of the most common neurodegenerative disorders, and is caused by the death of dopamine neurons and neuroinflammation in the striatum and substantia nigra. Furthermore, the inflammatory response in PD is closely related to glial cell activation. This study examined the neuroprotective effects of the barbiturate derivative, MHY2699 [5-(4-hydroxy 3,5-dimethoxybenzyl)-2 thioxodihydropyrimidine-4,6(1H,5H)-dione] in a mouse model of PD. MHY2699 ameliorated MPP⁺-induced astrocyte activation and ROS production in primary astrocytes and inhibited the MPP⁺-induced phosphorylation of MAPK and NF-κB. The anti-inflammatory effects of MHY2699 in protecting neurons were examined in an MPTP-induced mouse model of PD. MHY2699 inhibited MPTP-induced motor dysfunction and prevented dopaminergic neuronal death, suggesting that it attenuated neuroinflammation. Overall, MHY2699 has potential as a neuroprotective treatment for PD.

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