• Biomolecules & Therapeutics
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• v.22 no.4
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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.

• Biomolecules & Therapeutics
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• v.19 no.1
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• pp.118-125
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• 2011

Free radical scavenging and antioxidants have attracted attention as a way to prevent the progression of Parkinson's disease (PD). This study was carried out to investigate the effects of n-hexane fraction from Laurus nobilis L. (Lauraceae) leaves (HFL) on dopamine (DA)-induced intracellular reactive oxygen species (ROS) production and apoptosis in human neuroblastoma SH-SY5Y cells. Compared with apomorphine (APO, $IC_{50}=18.1\;{\mu}M$) as a positive control, the HFL $IC_{50}$ value for DA-induced apoptosis was $3.0\;{\mu}g/ml$, and two major compounds from HFL, costunolide and dehydrocostus lactone, were $7.3\;{\mu}M$ and $3.6\;{\mu}M$, respectively. HFL and these major compounds significantly inhibited ROS generation in DA-induced SH-SY5Y cells. A rodent 6-hydroxydopamine (6-OHDA) model of PD was employed to investigate the potential neuroprotective effects of HFL in vivo. 6-OHDA was injected into the substantia nigra of young adult rats and an immunohistochemical analysis was conducted to quantitate the tyrosine hydroxylase (TH)-positive neurons. HFL significantly inhibited 6-OHDA-induced TH-positive cell loss in the substantia nigra and also reduced DA induced $\alpha$-synuclein (SYN) formation in SH-SY5Y cells. These results indicate that HFL may have neuroprotective effects against DA-induced in vitro and in vivo models of PD.

• Journal of Ginseng Research
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• v.33 no.2
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• pp.111-114
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• 2009

The six phenolic-compound (ascorbic acid, maltol, esculetin,p-coumaric acid, cinnamic acid, and quercetin) contents of Panax ginseng c.A. Meyer were determined in this study. The results showed that the ascorbic acid, cinnamic acid, and esculetin contents of Panax ginseng C.A. Meyer are higher than those of the other ingredients. Among these compounds, ascorbic acid and cinnamic acid significantly inhibited LPS-induced nitric oxide production in the RAW 264.7 cells. Cinnamic acid also effectively inhibited the oxidative damages in the human neuroblastoma SH-SY5Y cells. Although this study examined the neuroprotective and anti-inflammatory activities using only one kind of cells, its results suggest that cinnarnic acid potently contributes to the neuroprotective and anti-inflammatory properties of Panax ginseng C.A. Meyer.

• BMB Reports
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• v.52 no.7
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• pp.439-444
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• 2019

Although hypoxic/ischemic injury is thought to contribute to the incidence of Alzheimer's disease (AD), the molecular mechanism that determines the relationship between hypoxia-induced ${\beta}$-amyloid ($A{\beta}$) generation and development of AD is not yet known. We have now investigated the protective effects of N,4,5-trimethylthiazol-2-amine hydrochloride (KHG26702), a novel thiazole derivative, on oxygen-glucose deprivation (OGD)-reoxygenation (OGD-R)-induced $A{\beta}$ production in SH-SY5Y human neuroblastoma cells. Pretreatment of these cells with KHG26702 significantly attenuated OGD-R-induced production of reactive oxygen species and elevation of levels of malondialdehyde, prostaglandin $E_2$, interleukin 6 and glutathione, as well as superoxide dismutase activity. KHG26702 also reduced OGD-R-induced expression of the apoptotic protein caspase-3, the apoptosis regulator Bcl-2, and the autophagy protein becn-1. Finally, KHG26702 reduced OGD-R-induced $A{\beta}$ production and cleavage of amyloid precursor protein, by inhibiting secretase activity and suppressing the autophagic pathway. Although supporting data from in vivo studies are required, our results indicate that KHG26702 may prevent neuronal cell damage from OGD-R-induced toxicity.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.1
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• pp.139-145
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• 2005

This study was performed to investigate the effect of Bohyulanshin-tang on brain-derived neurotophic factor(BDNF) expression in SK-N-SH (immortalized human neuroblastoma) cell line. MTT-based cytotoxicity assay revealed that cells of 0.1 mg/ml group and 1 mg/ml group significantly increased compared with Control group. Westren blotting and RT-PCR analysis showed that Bohyulanshin-tang significantly increased BDNF mRNA expression of 0.1 mg/ml group and 1 mg/ml group compared with Control group. Another analysis revealed that Bohyulanshin-tang significantly increased BDNF expression of 0.1 mg/ml group and 1 mg/ml group compared with Control group. These results showed that cell-protective abilities and cell-proliferating effects of Bohyulanshin-tang approached that of Fluoxetine.

• The Korean Journal of Physiology and Pharmacology
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• v.11 no.5
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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.

• Journal of Microbiology and Biotechnology
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• v.23 no.2
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• pp.274-277
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• 2013

The unique properties of graphene have earned much interest in the fields of materials science and condensedmatter physics in recent years. However, the biological applications of graphene remain largely unexplored. In this study, we investigate the cell culture conditions, which are exposed to graphene onto glass and $SiO_2$/Si using human nerve cell line, SH-SY5Y. Cell viability was 84% when cultured on glass and $SiO_2$/Si coated with graphene as compared to culturing on polystyrene surface. Fluorescence data showed that the presence of graphene did not influence cell morphology. These findings suggest that graphene may be used for biological applications.

• Journal of Life Science
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• v.13 no.5
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• pp.642-650
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• 2003

To develop a new approach to the treatment of neuroblastoma cells we evaluated the effect of cAMP on the Ewing's sarcoma cell line CHP-100. We observed that the proliferation-inhibitory effect of cAMP analogs was due to cell cycle arrest and induction of apoptosis, which was confirmed by observing the morphological changes and DNA fragmentation. DNA flow cytometric analysis revealed that cAMP arrested the cell cycle progression at the G1 phase, which effects were associated with inhibition of phosphorylation of retinoblastoma protein (pRB) and enhanced binding of pRB and the transcription factor E2F-1. cAMP also suppressed the cyclin-dependent kinase (Cdk) 2 and cyclin E-associated kinase activity without changes of their expressions. Furthermore, cAMP induced the levels of Cdk inhibitor $p21^{WAF1/CIP1$ expression and p21 proteins induced by cAMP were associated with Cdk2. Overall, our results identify a combined mechanism involving the inhibition of pRB phosphorylation and induction of p21 as targets for cAMP, and this may explain some of its anti-cancer effects.

• Journal of Life Science
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• v.28 no.5
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• pp.517-523
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• 2018

Elevated levels of cortisol caused by chronic stress may lead to neuron damage in the hippocampus by activating the glucocorticoid receptors (GRs). In cortisol-deficient animals, corticosterone is known to function as a stress hormone. In humans however, corticosterone is considered a precursor of aldosterone and a glucocorticoid with similar properties to cortisol. Recently, many studies have been conducted on the role of cortisol and other synthetic glucocorticoids like dexamethasone in humans, but the exact function of corticosterone is unknown. This study examined the viability of human neuroblastoma SH-SY5Y cells treated with various concentrations of corticosterone for 24 and 48 hr via MTT assay. The MTT-assay results showed that corticosterone had an antiproliferation effect on SH-SY5Y cells at higher concentrations (500 and $1,000{\mu}M$), while in lower concentrations ($100{\mu}M$), it showed no antiproliferation effect. Cytotoxicity analysis of extracts from three medicinal crops (Liriope muscari, Schisandra chinensis, and Wolfiporia extensa) revealed that they all possessed deleterious effects on SH-SY5Y cells depending on dosage. However, it was observed that, at a concentration of $500{\mu}g/ml$, Liriope muscari attenuated the corticosterone-induced antiproliferation on SY-SH5Y cells and restored cell growth after 48 hours of treatment. The study examined the synergistic effect of six mixtures each containing $500{\mu}g/ml$ of Liriope and various concentrations of Schisandra (50 or $100{\mu}g/ml$) and Wolfiporia (10, 30, and $50{\mu}g/ml$). The results showed minor growth-restoration activity but less than that of Liriope muscari only, suggesting that Schisandra and Wolfiporia had no additive or synergistic effects.

• The Journal of Korean Obstetrics and Gynecology
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• v.23 no.3
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• pp.1-13
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• 2010

Purpose: These studies were undertaken to evaluate the anti-oxidative and neuroprotective effects of Gamisoyo-san(GMSYS). Materials and Methods: We studied the antioxidant effects of GMSYS by assessing the DPPH free radical and the ABTS radical cation inhibition activities, the total polyphenolic contents(TPC). To evaluate the effects of GMSYS in the human neuroblastoma cells, we measured the cell viabilities in SH-SY5Y cells treated with GMSYS. Then we observed the protective effects of GMSYS against 6-OHDA induced neurotoxicity in SH-SY5Y cells. To confirm the neuroprotective effects of GMSYS in the primary culture of mesencephalic dopaminergic cells, we counted the TH-immunopositive cells and measured the NO and TNF-$\alpha$ after the treatment of GMSYS and 6-OHDA. Results: The DPPH free radical and the ABTS radical cation inhibition activities were increased in a dose dependent manner and the IC50 were $133.60{\mu}g/m{\ell}$ and $106.20{\mu}g/m{\ell}$, respectively. The TPC was 0.78%. There were no differences between the various concentrations of GMSYS and the control in the cell viability of SH-SY5Y cells. The neuroprotective effects of GMSYS were shown in the co-treatment group at the low concentrations of $25{\mu}g/m{\ell}$ and the post-treatment group at all concentrations. After the treatment of GMSYS and 6-OHDA in the primary culture of dopaminergic cells, the TH-immunopositive cells were significantly increased in $0.2{\mu}g/m{\ell}$ of GMSYS than the 6-OHDA group. The NO and TNF-$\alpha$ were significantly decreased in $0.2{\mu}g/m{\ell}$ of GMSYS than the 6-OHDA group. Conclusions: This study shows that GMSYS has the antioxidant and neuroprotective effects, especially in the mesencephalic dopaminergic cells. We suggest that GMSYS could be useful for the treatment of postmenopausal depression related with the degeneration of dopamine neuron.