• 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.

• Biomolecules & Therapeutics
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• 제19권1호
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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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• 제33권2호
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• pp.111-114
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• 2009

백삼 및 백삼에 함유된 페놀성 성분 6종의 산화적 손상에 대한 신경세포보호효과와 LPS로 유도된 대식세포에서의 NO 생성억제효과를 검정한 결과 백삼 추출물은 두가지 모두에서 농도의존적인 효과를 나타내었다. 백삼에 함유된 페놀성 성분 중에는 cinnamic acid 및 maltol이 우수한 신경세포보호활성을 나타내었고 NO 생성억제효과는 ascorbic acid 및 cinnamic acid가 높았다. 또한 페놀성성분의 백삼내 함량을 정량한 결과 ascorbic acid, cinnamic acid, esculetin가 다른 성분들에 비하여 비교적 많이 함유되어 있었으며 이를 종합하여 볼 때 백삼의 신경보호효과 및 항염증효과에는 높은 함량 및 우수한 활성을 보이는 성분인 cinnamic aicd가 크게 기여하는 것으로 판단된다.

• BMB Reports
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• 제52권7호
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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.

• 동의생리병리학회지
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• 제19권1호
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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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• 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.

• Journal of Microbiology and Biotechnology
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• 제23권2호
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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.

• 생명과학회지
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• 제13권5호
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• pp.642-650
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• 2003

인체 신경아세포종의 성장에 미치는 cAMP의 영향을 조사하기 위하여 Ewing's sarcoma 세포주인 CHP-100 세포에 dibutyry1-cAMP 및 8-bromo-cAMP를 처리하였다. 두 종류의 cAMP analog처리 시간 증가에 따라 CHP-100 세포의 증식이 처리 시간 의존적으로 억제되었으며, 이는 핵의 형태변화 및 DNA 단편화 현상을 수반한 apoptosis 유발과 연관성이 있었다. 또한 DNA flow cytometry 분석결과 cAMP는 세포주기 G1기 특이적 arrest를 유발하였다. cAMP 처리에 의하여 retinoblastoma 단백질(pRB)의 인산화가 억제되었으며, 전사조절인자 E2F-1과의 결합이 증대되었다. cAMP는 cyclin-dependent kinase (Cdk) 2 및 cyclin E 단백질의 발현변화에는 영향을 미치지 않았으나, 그들의 kinase 활성은 처리시간 의존적으로 매우 감소되었다. 또한 cAMP 처리에 의하여 Cdk inhibitor인 $p21^{WAF1/CIP1$의 발현이 증가되었으며, 증가된 p21 단백질은 Cdk2와 강한 결합을 형성하고 있었다. 이상의 결과에서 cAMP의 암세포 성장억제 효과에 pRB 및 p21이 매우 중요한 역할을 함을 알 수 있었다.

• 생명과학회지
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• 제28권5호
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• pp.517-523
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• 2018

만성적 스트레스가 있는 상황에서, 과잉 생산된 cortisol은 glucocorticoid receptor (GR)를 활성화시킴으로써 해마(hippocampus)에 있는 신경 세포에 손상을 줄 수 있다. Cortisol을 생성하지 못하는 동물들의 경우, corticosterone이 스트레스 호르몬의 역할을 하는 것으로 알려져 있다. 한편, 인간의 경우, corticosterone은 aldosterone의 전구물질 이거나 cortisol과 비슷한 특성을 가지는 하나의 glucocorticoid로만 여겨져 왔다. 최근 인간을 대상으로 cortisol과 dexamethasone과 같은 합성 glucocorticoid의 기능에 관한 연구가 많이 이루어져 왔으나, corticosterone의 정확한 기능에 대하여 많이 알려져 있지 않다. 본 연구에서 corticosterone을 여러 농도로 SH-SY5Y 세포에 처리한 후 24시간과 48시간 때 viability를 조사한 결과, 높은 농도($500{\mu}M$과 $1,000{\mu}M$)에서 SH-SY5Y 세포의 성장 억제가 관찰된 반면, 낮은 농도($100{\mu}M$)에선 그 효과가 나타나지 않았다. 맥문동, 오미자, 복신 열수 추출물에 대한 세포 독성을 실시한 결과, 세 시료 모두 농도가 높아질수록 높은 세포 독성을 보였다. 한편, $500{\mu}g/ml$의 맥문동은 corticosterone에 의해 유도된 세포 성장 억제를 완화시켜 세포 성장을 회복시키는 효과를 보였다. 마지막으로, 맥문동 $500{\mu}g/ml$에 오미자와 복신의 농도를 달리하여 제조한 여러 혼합물의 시너지 효과를 알아본 결과, 대부분 혼합물이 약간의 효과를 보이긴 했으나, 음성 대조군 수준만큼 회복되지는 않았다.

• 대한한방부인과학회지
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• 제23권3호
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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.