• Journal of Microbiology and Biotechnology
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• 제30권3호
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• pp.359-367
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• 2020

Neurodegenerative disorders in the elderly are characterized by gradual loss of memory and cognitive function. Oxidative stress caused by reactive oxygen species is associated with progressive neuronal cell damage and death in Alzheimer's disease, one of the most common neurodegenerative disorders. An edible brown seaweed, Ecklonia cava, contains a variety of biologically active compounds such as phlorotannins. In this study, we comparatively evaluated the total phenolic content, antioxidant capacity, and neuroprotective effects of the phlorotannin-rich extract from E. cava (PEEC). The total phenolic content of PEEC and dieckol was 810.8 mg gallic acid equivalents (GAE)/g and 996.6 mg GAE/g, respectively. Antioxidant capacity of PEEC was 1,233.8 mg vitamin C equivalents (VCE)/g and 392.1 mg VCE/g determined using ABTS and DPPH assays, respectively, while those of dieckol were 2,238.4 mg VCE/g and 817.7 mg VCE/g. High-performance liquid chromatography results revealed 48.08 ± 0.67 mg dieckol/g of PEEC. PEEC had neuroprotective effects in pheochromocytoma (PC-12) and human neuroblastoma (SH-SY5Y) cells against H₂O₂- and AAPH-induced oxidative damage, partly due to reduced intracellular oxidative stress. PEEC treatment inhibited acetylcholinesterase and butyrylcholinesterase in a dose-dependent manner. Taken together, these findings suggest that PEEC is a good source of antioxidants and neuroprotective materials.

• Biomolecules & Therapeutics
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• 제22권4호
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• pp.275-281
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• 2014

Autophagy is a series of catabolic process mediating the bulk degradation of intracellular proteins and organelles through formation of a double-membrane vesicle, known as an autophagosome, and fusing with lysosome. Autophagy plays an important role of death-survival decisions in neuronal cells, which may influence to several neurodegenerative disorders including Parkinson's disease. Chebulagic acid, the major constituent of Terminalia chebula and Phyllanthus emblica, is a benzopyran tannin compound with various kinds of beneficial effects. This study was performed to investigate the autophagy enhancing effect of chebulagic acid on human neuroblastoma SH-SY5Y cell lines. We determined the effect of chebulagic acid on expression levels of autophagosome marker proteins such as, DOR/TP53INP2, Golgi-associated ATPase Enhancer of 16 kDa (GATE 16) and Light chain 3 II (LC3 II), as well as those of its upstream pathway proteins, AMP-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR) and Beclin-1. All of those proteins were modulated by chebulagic acid treatment in a way of enhancing the autophagy. Additionally in our study, chebulagic acid also showed a protective effect against 1-methyl-4-phenylpyridinium ($MPP^+$) - induced cytotoxicity which mimics the pathological symptom of Parkinson's disease. This effect seems partially mediated by enhanced autophagy which increased the degradation of aggregated or misfolded proteins from cells. This study suggests that chebulagic acid is an attractive candidate as an autophagy-enhancing agent and therefore, it may provide a promising strategy to prevent or cure the diseases caused by accumulation of abnormal proteins including Parkinson's disease.

• The Korean Journal of Physiology and Pharmacology
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• 제11권5호
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• pp.171-174
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• 2007

Neuronal death is a common characteristic hallmark of a variety of neurodegenerative disorders including Alzheimer's disease and Parkinson's disease. However, there have been no effective drugs to successfully prevent neuronal death in those diseases, whereas oriental medicinal plants have to possess valuable therapeutic potentials to treat neurodegenerative diseases. In the present study, in an attempt to provide neuroprotective agents from natural plants, 80% methanol extracts of a wide range of medicinal plants, which are native to Jeju Island in Korea, were prepared and their protective effects on hydrogen peroxide-induced apoptotic cell death were examined. Among those tested, extracts from Smilax china and Saururus chinesis significantly decreased hydrogen peroxide-induced apoptotic cell death. The extracts attenuated hydrogen peroxide($H_2O_2$)-induced caspase-3 activation in a dose-dependent manner. Further, plant extracts restored $H_2O_2$-induced depletion of intracellular glutathione, a major endogenous antioxidant. The data suggest that Jeju native medicinal plants could potentially be used as therapeutic agents for treating or preventing neurodegenerative diseases in which oxidative stress is implicated.

• BMB Reports
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• 제47권10호
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• pp.569-574
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• 2014

Heme oxygenase-1 (HO-1) degrades heme to carbon dioxide, biliverdin, and $Fe^{2+}$, which play important roles in various biochemical processes. In this study, we examined the protective function of HO-1 against oxidative stress in SH-SY5Y cells and in a Parkinson's disease mouse model. Western blot and fluorescence microscopy analysis demonstrated that PEP-1-HO-1, fused with a PEP-1 peptide can cross the cellular membranes of human neuroblastoma SH-SY5Y cells. In addition, the transduced PEP-1-HO-1 inhibited generation of reactive oxygen species (ROS) and cell death caused by 1-methyl-4-phenylpyridinium ion ($MPP^+$). In contrast, HO-1, which has no ability to transduce into SH-SY5Y cells, failed to reduce $MPP^+$-induced cellular toxicity and ROS production. Furthermore, intraperitoneal injected PEP-1-HO-1 crossed the blood-brain barrier in mouse brains. In a PD mouse model, PEP-1-HO-1 significantly protected against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced toxicity and dopaminergic neuronal death. Therefore, PEP-1-HO-1 could be a useful agent in treating oxidative stress induced ailments including PD.

• The Korean Journal of Physiology and Pharmacology
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• 제2권5호
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• pp.565-572
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• 1998

The present study was to evaluate the protective effects of bromocriptine, which is known as $D_2$ dopamine receptor agonist and used for the treatment of patients with Parkinson's disease (PD), on 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in vitro and in vivo. Lipid peroxidation product (malondialdehyde; MDA) produced by the administration of 6-OHDA was profoundly reduced following the treatment of bromocriptine in a dose-dependent manner in rabbit brain homogenate. Quinone formation by 6-OHDA autoxidation was also attenuated, and its effect was as potent as other antioxidants. Pretreatment of bromocriptine reduced the cytotoxicity of 6-OHDA on SH-SY5Y neuroblastoma cell lines dose-dependently. The loss of striatal dopamine and its metabolite, DOPAC (dihydroxyphenylacetic acid) as well as increase of MDA production caused by intrastriatal injection of 6-OHDA was significantly recovered following the treatment of bromocriptine. The present study clearly showed that bromocriptine had a protective action against 6-OHDA-induced neurotoxicity. These results suggest that bromocriptine has the antioxidant properties, which could be another advantage for delaying the progress of Parkinson's disease.

• 대한의생명과학회지
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• 제17권2호
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• pp.167-171
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• 2011

[ ${\alpha}$ ]synuclein (${\alpha}$-syn) is implicated in the pathogenesis of Parkinson's disease (PD) and other related diseases. We have previously reported that ${\alpha}$-syn binds to the cell membranes in a transient and reversible manner. However, little is known about the physiologic function and/or consequence of this association. Here, we examined whether chemically induced perturbations to the cellular membranes enhance the binding of ${\alpha}$-syn, based on hypothesis that ${\alpha}$-syn may play a role in maintenance of membrane integrity or repair. We induced membrane perturbations or alterations in ${\alpha}$-syn-overexpressing human neuroblastoma cells (SH-SY5Y) by treating the cells with hydrogen peroxide ($H_2O_2$) or oleic acid. In addition, membranes fractionated from these cells were perturbed by treating them with proteinase K or chloroform. Dynamic interaction of ${\alpha}$-syn to the membranes was analyzed by the chemical cross-linking assay that we developed in the previous study. We found that membrane interaction of ${\alpha}$-syn was increased upon treatment with membrane-perturbing reagents in a dose and time dependent manner. These results suggest that perturbations in the cellular membranes cause increased binding of ${\alpha}$-syn, and this may have significant implication in the physiological function of ${\alpha}$-syn in cells.

• 한국환경독성학회:학술대회논문집
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• 한국환경독성학회 2003년도 추계국제학술대회
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• pp.177-177
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• 2003

Methylmercury (MeHg) is a well-known neurotoxicant that causes severe damage to the central nervous system in humans. Many reports have shown that MeHg is poisonous to human body through contaminated foods and has released into the environment. Despite many studies on the pathogenesis of MeHg-induced central neuropathy, no useful mechanism of toxicity has been established so far. In this study, suppressive subtractive hybridization (SSH) was performed to identify differentially expressed genes on human neuroblastoma cell line, SH-SY5Y treated with DMSO and MeHg (6.25 uM) for 6 hr. Differentially expressed cDNA clones were sequenced and were screened by dot blot to eliminate false positive clones. 13 of 35 screened genes were confirmed using real time RT-PCR. These genes include EB1,90-kDa heat-shock protein, chromosome condensation-related SMC-associated protein and brain peptide Al, etc. Analysis of these genes may provide an insight into the neurotoxic effects of MeHg in human neuronal cells and a possibility to develop more efficient and exact monitoring system of heavy metals as ubiquitous environmental pollutants.

• Journal of Microbiology and Biotechnology
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• 제29권1호
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• pp.30-36
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• 2019

Numerous studies have reported that enteric neurons involved in controlling neurotransmitter secretion and motility in the gut critically contribute to the progression of gut inflammation. Clostridium difficile toxins, which cause severe colonic inflammation, are also known to affect enteric neurons. Our previous study showed that C. difficile toxin A directly induces neural cell toxicities, such as viability loss and apoptosis. In the current study, we attempted to identify a potent inhibitor of toxin A-induced neural cell toxicity that may aid in managing toxin A-induced gut inflammation. In our recent study, we found that the Korea dung beetle-derived antimicrobial peptide CopA3 completely blocked neural cell apoptosis caused by okadaic acid or 6-OHDA. Here, we examined whether the antimicrobial peptide CopA3 inhibited toxin A-induced neural cell damage. In neuroblastoma SH-SY5Y cells, CopA3 treatment protected against both apoptosis and viability loss caused by toxin A. CopA3 also completely inhibited activation of the pro-apoptotic factor, caspase-3. Additionally, CopA3 rescued toxin A-induced downregulation of neural cell proliferation. However, CopA3 had no effect on signaling through ROS/p38 $MAPK/p27^{kip1}$, suggesting that CopA3 inhibits toxin A-induced neural cell toxicity independent of this well-characterized toxin A pathway. Our data further suggest that ability of CopA3 to rescue toxin A-induced neural cell damage may also ameliorate the gut inflammation caused by toxin A.

• The Korean Journal of Physiology and Pharmacology
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• 제10권6호
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• pp.309-315
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• 2006

The protective effects of baicalein, one of the flavonoids in Scutellaria baicalensis Georgi, were evaluated against 6-hydroxydopamine (6-OHDA)-induced neuronal damage in mice and cultured human neuroblastoma cells. Nigrostriatal damage was induced by stereotaxically injecting 6-OHDA into the right striatum. Baicalein was administered intraperitoneally 30 min before and 90 min after lesion induction. Animals received a further daily injection of baicalein for 3 consecutive days. Two weeks after 6-OHDA injection, contralateral rotational asymmetry was observed by apomorphine challenge in lesioned mice. Tyrosine hydroxylase (TH) immunohistochemistry revealed a significant loss of terminals in lesioned striatum and the reduction of the numbers of TH-positive cell in the ipsilateral substantia nigra (SN). In addition, the levels of dopamine (DA) and DA metabolites were reduced and lipid peroxidation was increased in lesioned striatum. However, baicalein treatment reduced apomorphine-induced rotational behavior in 6-OHDA-lesioned mice, and increased TH immunoreactivity in the striatum and SN, and DA levels in lesioned striatum. Lipid peroxidation induced by 6-OHDA was also inhibited by baicalein treatment. Furthermore, when SH-SY5Y human neuroblastoma cells were treated with baicalein, 6-OHDA-induced cytotoxicity and reactive oxygen species (ROS) production were significantly reduced. These results indicate that baicalein effectively protects 6-OHDA-induced neuronal damage through antioxidant action.

• Journal of Nutrition and Health
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• 제48권5호
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• pp.451-456
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• 2015

Purpose: Neuronal apoptotic events induced by aging and hypoxic/ischemic conditions is an important risk factor in neurodegenerative diseases such as ischemia stroke and Alzheimer's disease. The peel of Citrus sunki Hort. ex Tanaka has long been used as a traditional medicine, based on multiple biological activities including anti-oxidant, anti-inflammation, and anti-obesity. In the current study, we examined the actions of fermented C. sunki peel extract against cobalt chloride ($CoCl_2$)-mediated hypoxic death in human neuroblastoma SH-SY5Y cells. Methods: Cell viability was measured by trypan blue exclusion. Expression of apoptosis related proteins and release of cytochrome c were detected by western blot. Production of intracellular reactive oxygen species (ROS) and apoptotic morphology were examined using 2',7'-dichlorofluorescin diacetate (DCF-DA) and 4',6-diamidino-2-phenylindole (DAPI) staining. Results: Exposure to $CoCl_2$, a well-known mimetic agent of hypoxic/ischemic condition, resulted in neuronal cell death via caspase-3 dependent pathway. Extract of fermented C. sunki peel significantly rescued the $CoCl_2$-induced neuronal toxicity with the cell viability and appearance of apoptotic morphology. Cytoprotection with fermented C. sunki peel extract was associated with a decrease in activities of caspase-3 and cleavage of poly (ADP ribose) polymerase (PARP). In addition, increase in the intracellular ROS and release of cytochrome c from mitochondria to the cytosol were inhibited by treatment with extract of fermented C. sunki peel. Conclusion: Based on these data, fermented C. sunki peel extract might have a protective effect against $CoCl_2$-induced neuronal injury partly through generation of ROS and effectors involved in mitochondrial mediated apoptosis.