• Journal of Microbiology and Biotechnology
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• v.30 no.3
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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.

• Korean Journal of Medicinal Crop Science
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• v.17 no.5
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• pp.341-345
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• 2009

Cerebral ischemia results from a transient or permanent reduction in cerebral blood flow that decreases oxygen and glucose supply. When the cellular oxygen supply is reduced to critical level, damage to cells and induction of cell death are occurred by excitotoxicity, oxidative stress and inflammation. Ischemia remains one of the leading causes of death, but there is no effective treatment that might protect neurons gainst ischemia by interrupting the cascade of cell death. In this study, human neuroblastoma SH-SY5Y cells are exposed to oxygen and glucose deprivation (OGD) followed by reoxgenation. OGD can mimic the acute restriction of metabolite and oxygen supply caused by ischemia and is widely used as a model of ischemic conditions. SH-SY5Y cells are treated samples at the commencement of OGD to achieve different final concentrations, and cell viabilities were quantified using the measurement of flow cytometry analysis. Of those tested, the extracts of Polygala tenuifolia (roots), Dictamnus dasycarpus (barks), Polygala tenuifolia (roots), Eucommia ulmoides (branches), Eucommia ulmoides (barks), Poria cocos (whole), Sophora flavescens (roots) showed neuroprotective effects, with $EC_{50}$ values of $4.5{\pm}0.6$, $7.9{\pm}1.5$, $10.5{\pm}0.7$, $18.4{\pm}1.9$, $19.6{\pm}0.3$, $21.6{\pm}1.9$, and $30.7{\pm}3.9{\mu}g/m{\ell}$, respectively.

• Biomolecules & Therapeutics
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• v.13 no.4
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• pp.256-262
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• 2005

We examined the signaling molecules involved in the 6-hydroxydopamine (6-OHDA)-induced neuronal cell death and increase in cellular glutathione (GSH) level in SK-N-SH cells. The 6-OH-DA-induced cell death was significantly prevented by the pretreatment with N-acetylcysteine (NAC), a thiol antioxidant, and BAPTA, an intracellular $Ca^{2+}$ chelator. Although 6-OHDA induced ERK phosphorylation, the pretreatment with PD98059, an ERK inhibitor, did not block 6-OHDA-induced cell death. In addition, the 6-OHDA-induced activation of caspase-3, a key signal for apoptosis, was blocked by the pretreatment with NAC and BAPTA. While the level of reactive oxygen species (ROS) was significantly increased in the 6-OHDA-treated cells, the cellular GSH level was not altered for the first 6-hr exposure to 6-OHDA, but after then, the level was significantly increased, which was also blocked by the pretreatment with NAC and BAPTA, but not by PD98059. Depletion of GSH by pretreating the cells with DL-buthionine-(S,R)-sulfoximine (BSO), a glutathione synthesis inhibitor, rather significantly potentiated the 6-OHDA-induced death. In contrast to the pretreatment with NAC, 6-OHDA-induced cell death was not prevented by the post-treatment with NAC 30 min after 6-OHDA treatment. The results indicate that the GSH level which is increased adaptively by the 6-OHDA-induced ROS and intracellular $Ca^{2+}$ is not enough to overcome the death signal mediated through ROS-$Ca^{2+}$ -caspase pathway.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.04a
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• pp.199-199
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• 1994

Thioglycerol과 glycerol로부터 rac-1-S-octa-decyl-2-O-palmitoyl-1-S-thioglycerol-3-phosphate (DL -PTBA-P)와 rac-1-O-octadecyl-2-O-palmitoyl-g1ycerol-3-phosphate (DL-PBA-P)등을 합성하였고, 이들에 ara-C 유도체인 ara-CMP morpholidate를 반응시켜 최종 산물인 ara-CDP-DL-PCA, ara-CDP-DL-PBA, ara-CDP-DL-PTCA 및 ara-CDP-DL-PTBA등을 합성하였다. 이들 최종산믈의 항암효과는 L1210 lymphoid leukemia, colon 26 carcioma, M5076 sarcoma, C-1300 neuroblastoma, 3-Lewis lung carcinoma, WEHI-3B leukemia, human colon cancer, hum an pancreatic cancer 등의 암세포주를 사용하여 실험하였다. L1210를 DB/2J의 뇌막 또는 복강, DBA/1J의 복강내에 이식하여 ara-C, Ehss thioether lipid의 ara-C 유도체 (ara-CDP-L-DP, ara-CDP-DL-PCA, ara-CDP-DL-PBA, ara -CDP-DL-PTCA, ara-CDP-D-PTBA, ara-CDP-L-PTBA, ara-CDP-DL-PTBA)를 단일 투여 또는 중복 투여하였고, 3-Lewis는 C57BL/6 의 발바닥 피하, colon26은 BALB/C의 견갑상부 히아조직, M5076은 C57BL/6의 피하, WEHI-3B는 BALB/C의 복강, C-1300는 A/strong Ros에 각각 이식한 후 ara-C 또는 ara-CDP-DL-PTBA를 단일 또는 중복 투여하였다.

• Biomolecules & Therapeutics
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• v.19 no.3
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• pp.288-295
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• 2011

Amyloid beta ($A{\beta}$)-induced neurotoxicity is a major pathological mechanism of Alzheimer's disease (AD). In this study, we investigated the inhibitory effect of L-theanine, a component of green tea (Camellia sinensis) on $A{\beta}_{1-42}$-induced neurotoxicity and oxidative damages of macromolecules. L-theanine inhibited $A{\beta}_{1-42}$-induced generation of reactive oxygen species, and activation of extracellular signal-regulated kinase and p38 mitogenic activated protein kinase as well as the activity of nuclear factor kappa-B. L-theanine also signifi cantly reduced oxidative protein and lipid damage, and elevated glutathione level. Consistent with the reduced neurotoxic signals, L-theanine (10-50 ${\mu}g$/ml) concomitantly attenuated $A{\beta}_{1-42}$ (5 ${\mu}M$)-induced neurotoxicity in SK-N-MC and SK-N-SH human neuroblastoma cells. These data indicate that L-theanine on $A{\beta}$-induced neurotoxicity prevented oxidative damages of neuronal cells, and may be useful in the prevention and treatment of neurodegenerative disease like AD.

• Biomolecules & Therapeutics
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• v.15 no.1
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• pp.27-33
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• 2007

The psychopharmacological profile of ginsenosides has not yet been confirmed systematically although various neuropharmacological activities associated with them have been investigated. In the present study, the psychological activities of Rb1 were investigated to evaluate whether it can be used in treatment or prevention of psychological disorders. Rb1 was intravenously injected at doses of O.2,2,5 and 10 mg/kg. The effects of Rb1 on the $Cl^-$ ion influx were investigated using IMR-32 human neuroblastoma cells. Moreover, locomotor activity, forced swimming activity, activity on rotating rod and activity in elevated plus-maze were tested in mice. Rb1 increased the $Cl^-$ influx into the intracell region in a dose-dependent manner. Rb1 did not cause change in behavior in total open field when locomotor activity was tested, however it increased activities, especially, such as rearing frequency in center area. Administration of Rb1 at 0.2 mg/kg significantly reduced activities on rotating rod however administration at high dosages had no effect on them. Rb1 administration decreased animal immobile time in a water chamber in a dose dependent manner, and increased the strong mobile time of animals. In conclusion, the present results demonstrate that Rb1 contributes to the psychopharmacological effects of ginseng and may be used in treatment or prevention of psychological disorders such as anxiety or depression.

• The Korean Journal of Physiology
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• v.29 no.2
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• pp.301-307
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• 1995

To explore electrophysiological properties of the ${\delta}-Opioid$ receptors artificially expressed in the mammalian cell, effect of an opioid agonist DPDPE $(1\;{\mu}M)$ on the voltage-sensitive outward currents was examined in the HEK293 (human embryonic kidney) cells transfected with ${\delta}-Opioid$ receptor cDNA cloned from NG-108-15 $(neuroblastoma\;{\times}\;glioma\;hybrid)$ cDNA library. Also studied were effects of 8-bromo-cyclic AMP and naloxone on DPDPE-induced changes in the voltage sensitive outward current. The voltage sensitive outward currents were recorded using perforated patch technique at room temperature. In the non-transformed HEK293 cells, DPDPE did not alter voltage sensitive outward current, indicating that no native ${\delta}-Opioid$ receptor had been developed. However, $(1\;{\mu}M)$ DPDPE remarkably increased the voltage sensitive outward current in the transformed HEK293 cells. The increment in voltage sensitive outward current peaked in $7{\sim}10\;minutes$ after DPDPE application, and the maximum DPDPE-activated outward current $(313.1{\pm}12.3\;pA)$ was recorded when the membrane potential was depolarized to +70mv. Following pretreatment of the transformed HEK293 cells with 1 mM 8-bromo-cyclic AMP, DPDPE failed to increase the voltage sensitive outward currents. On the other hand, naloxone completely abolished DPDPE-activated voltage sensitive outward current in the transformed HEK293 cells. The results of present study suggest that in the transformed HEK293 cells an activation of the ${\delta}-Opioid$ receptors by an opioid agonist DPDPE increases the voltage-sensitive potassium current as a result of decrement in cyclic AMP level.

• 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.

• Journal of Ginseng Research
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• v.34 no.2
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• pp.138-144
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• 2010

Ginseng (Panax ginseng C.A. Meyer) has been shown to have anti-stress effects in animal studies. However, most studies have only managed to detect altered levels of biomarkers or enzymes in blood or tissue, and the actual molecular mechanisms by which ginseng exerts these effects remain unknown. In this study, the anti-oxidative effect of Korean red ginseng (KRG) was examined in human SK-N-SH neuroblastoma cells. Incubation of SK-N-SH cells with the oxidative stressor hydrogen peroxide resulted in significant induction of cell death. In contrast, pre-treatment of cells with KRG decreased cell death significantly. To elucidate underlying mechanisms by which KRG inhibited cell death, the expression of apoptosis-related proteins was examined by Western blot analysis. KRG pre-treatment decreased the expression of the pro-apoptotic gene caspase-3, whereas it increased expression of the anti-apoptotic gene Bcl-2. Consistent with this, immunoblot analysis showed that pre-treatment of the SK-N-SH cells with KRG inhibited expression of the pro-inflammatory gene cyclooxygenase 2 (COX-2). RT-PCR analysis revealed that the repression of COX-2 expression by KRG pre-treatment occurred at the mRNA level. Taken together, our data indicate that KRG can protect against oxidative stress-induced neuronal cell death by repressing genes that mediate apoptosis and inflammation.

• Toxicological Research
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• v.34 no.3
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• pp.267-279
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• 2018

Neurolathyrism is a neurodegenerative disorder characterized by spastic paraplegia resulting from the excessive consumption of Lathyrus sativus (Grass pea). ${\beta}$-N-Oxalyl-L-${\alpha},{\beta}$-diaminopropionic acid (L-ODAP) is the primary neurotoxic component in this pea. The present study attempted to evaluate the proteome-wide alterations in chick brain 2 hr and 4 hr post L-ODAP treatment. Proteomic analysis of chick brain homogenates revealed several proteins involved in cytoskeletal structure, signaling, cellular metabolism, free radical scavenging, oxidative stress and neurodegenerative disorders were initially up-regulated at 2 hr and later recovered to normal levels by 4 hr. Since L-ODAP mediated neurotoxicity is mainly by excitotoxicity and oxidative stress related dysfunctions, this study further evaluated the role of L-ODAP in apoptosis in vitro using human neuroblastoma cell line, IMR-32. The in vitro studies carried out at $200{\mu}M$ L-ODAP for 4 hr indicate minimal intracellular ROS generation and alteration of mitochondrial membrane potential though not leading to apoptotic cell death. L-ODAP at low concentrations can be explored as a stimulator of various reactive oxygen species (ROS) mediated cell signaling pathways not detrimental to cells. Insights from our study may provide a platform to explore the beneficial side of L-ODAP at lower concentrations. This study is of significance especially in view of the Government of India lifting the ban on cultivation of low toxin Lathyrus varieties and consumption of this lentil.