• The Journal of Korean Medicine
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• v.25 no.2
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• pp.138-150
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• 2004

Objectives : Alzheimer's disease (AD) is a geriatric dementia that is widespread in old age. In the near future AD will be the biggest problem in public health service. Although a variety of oriental prescriptions, including Sesim-tang, have been traditionally utilized for the treatment of AD, their pharmacological effects and action mechanisms have not yet been fully elucidated. The present study investigated the effects of Sesim-tang on apoptotic cell death induced by CT105 (carboxy terminal 105 amino acid peptide fragment of APP) overexpression in SK-N-SH neuroblastoma cell lines. Methods: We studied the regenerative and inhibitory effects on Alzheimer's disease in CT105-induced SK-N-SH cell lines by Sesim-tang water extract. We examined for cell morphological pattern, DNA fragmentation, LDH activity assay, zymography assay, and immunohistochemistric analysis. Additionally, we investigated the association between the CT105 and neurite degeneration caused by CT105-induced apoptotic response in neurone cells. Results: Findings from our experiments have shown that Sesim-tang inhibits the synthesis or activities of CT105, which has neurotoxicities and apoptotic activities in the cell line. In addition, pretreatment with Sesim-tang ($>50\mu\textrm{g}/ml$ for 12 hours) partially prevented CT105-induced cytotoxicity in SK-N-SH cell lines. SK-N-SH cell lines overexpressed with CT105 exhibited remarkable apoptotic cell damage. Based on morphological observations by phase-contrast microscope and LDH activity measurements in the culture media, the CT105-induced cell death was significantly inhibited by Sesim-tang water extract. Sesim-tang was found to reduce the expression of APP and caspase-3 induced by CT105 in SK-N-SH cell lines and in rat hippocampus. Conclusions: As the result of this study, in the Sesim-tang group, apoptosis in the nervous system is inhibited, the repair against the degeneration of SK-N-SH cell lines by CT105 expression is promoted. Hence, Sesim-tang may be beneficial for the treatment of AD.

• Biomolecules & Therapeutics
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• v.19 no.3
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• pp.342-347
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• 2011

In the present study, the anticonvulsant effects of Artemisia capillaris Herba (AC) and its major constituent, esculetin (ECT), were tested and the mechanism studied. Locomotion, Myorelaxation, motor coordination and electroshock seizure experiment were conducted in mice. To identify the anticonvulsant mechanism effect of this drug, chemical-induced seizure in mice and the ionic movement in neuroblastoma cells were also observed. The ethanol extract of AC was orally administered to mice 30 min. prior to testing and ECT was intraperitoneally injected. AC and ECT treatment did not change locomotor activities as well as activities on the rota-rod, which indicates that they did not cause a sedative and myorelaxation effect. AC and ECT treatment increased threshold of convulsion induced by electroshock. AC treatment also inhibited convulsion induced by pentylenetetrazole. In the case of strychnine however, only high dose of AC treatment inhibited convulsion. AC and ECT treatment increased the $Cl^-$ influx into the intracellular area in a dose-dependent manner. On the other hand, bicuculline, a GABA antagonist, inhibited the $Cl^-$ influx induced by AC and ECT. These results indicate that ECT induces the anticonvulsive effect of AC extract through the GABAergic neuron.

• 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.

• IMMUNE NETWORK
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• v.3 no.2
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• pp.118-125
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• 2003

Background: Disialoganglioside GD2 is a tumor-associated antigen that is overexpressed on tumor cells of neuroectodermal origin, such as melanoma and neuroblastoma. Anti-idiotypic antibodies that mimic GD2 may induce more effective immune responses than GD2 antigen itself, because they are protein antigens and are known to be able to break immune tolerance. In this study, to explore the potential of anti-idiotypic antibodies as tumor vaccines, the ability of anti-idiotypic antibodies (Ab2) to induce anti-anti-idiotypic antibodies (Ab3) that bind to the original antigen GD2 was investigated. Methods: Six monoclonal anti-idiotypic antibodies (1A8, 1G5, 2B6, 3A4, 3D6, 3H9) to monoclonal antibody M2058, which is a monoclonal antibody to GD2, were produced in mice. Three (1A8, 3A4, 3H9) of them were selected based on their ability to inhibit the binding of Ab1 to D142.34 (murine melanoma cell expressing GD2). These 3 different Ab2 were injected into rabbits, and rabbit Ab3 induced by each of them were characterized. Results: Ab3-containing sera from two rabbits immunized with 1A8, 3A4, or 3H9 bound significantly (P<0.05) to D142.34 but not to B78.96 (GD2-negative cell), and bound significantly (P<0.05) to isolated GD2 but not to GD1a. Ab3-containing sera from two rabbits immunized with 3A4 or 3H9 inhibited significantly (P<0.05) the binding of Ab1 M2058 to D142.34, and inhibited significantly (P<0.05) the binding of Ab1 M2058 to the Ab2. Conclusion: These results suggest that anti-idiotypic antibodies 3A4 and 3H9 have a potential to be used as vaccines against tumors expressing GD2 by inducing GD2-specific antibodies (Ab3).

• Preventive Nutrition and Food Science
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• v.16 no.1
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• pp.18-23
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• 2011

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by neuronal loss and extracellular senile plaques containing $\beta$-amyloid peptide (A$\beta$). The deposition of the A$\beta$ peptide following proteolytic processing of amyloid precursor protein (APP) by $\beta$-secretase (BACE1) and $\gamma$-secretase is a critical feature in the progression of AD. Among the plant extracts tested, the ethanol extract of Petasites japonicus leaves showed novel protective effect on B103 neuroblastoma cells against neurotoxicity induced by A$\beta$, as well as a strong suppressive effect on BACE1 activity. Ethanol extracts of P. japonicus leaves were sequentially extracted with methylene chloride, ethyl acetate and butanol and evaluated for potential to inhibit BACE1, as well as to suppress A$\beta$-induced neurotoxicity. Exposure to A$\beta$ significantly reduced cell viability and increased apoptotic cell death. However, pretreatment with ethyl acetate fraction of P. japonicus leaves prior to A$\beta$ (50 ${\mu}M$) significantly increased cell viability (p<0.01). In parallel, cell apoptosis triggered by A$\beta$ was also dramatically inhibited by ethyl acetate fraction of P. japonicus leaves. Moreover, the ethyl acetate fraction suppressed caspase-3 activity to the basal level at 30 ppm. Taken together, these results demonstrated that P. japonicus leaves appear to be a useful source for the inhibition and/or prevention of AD by suppression of BACE1 activity and attenuation of A$\beta$ induced neurocytotoxicity.

• Journal of Chest Surgery
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• v.25 no.6
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• pp.598-604
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• 1992

Rhabdomyosarcoma is the most common soft tissue sarcoma in childhood and acounts for 6% to 15% of all cases of childhood cancer, Rhabdomyosarcoma in seventh most common form of childhood neoplasms, following acute leukemia, tumors of the central nervous system, lymphoma neuroblastoma, Wilm`s tumor, bone tumor. Rhabdomyosarcoma can arise anywhere in the body, but primary site in the thorax is relatively rare. We experienced a case of aveolar rhabdomyosarcoma arising from intercostal muscle, A 12 year-old woman was suffered from the intermittent left chest pain radiating to the scapular area and dyspnea, On physical examination, pulmonary friction rub was heard on the left upper lobe area. Qn adimission, the chest simple radiography revealed a 7 x 6, 5cm sized radio-opaque mass with pleural effusion in the superior mediastinum and the CT showed a well difined radio-opaque mass including the destructed 2nd rib and pleural effusion. The percutaneous tra-nsthoracic needle aspiration biopsy was likely to show blastoma. After the chemotherapy[vincristine, actinomycin-D, cyclophosphamde] was done to treat blastoma, the pleural effussion was subsided and the mass was slightly decreased by 4.5x 4. 5cm. For treatment and diagnosis, we performed en-bloc resection and the defected chest was reconstucted with Gortex patch. Grossly, the specimen was colored graysh-white and arised in between two ribs The microscopic findings showed that the tumor cells were small round with scant pinkish cytoplasm on the H-E stain and the tumor cell nests were grouped by reticulum fibers and showed alveolar pattern on the silver stain The electromicroscopic finding presented that the cytoplasm contained tangled fibrillar and flocculent materials. The histopathologic findings were compatable with laveolar rhabdomyosarcoma. She was discharged without any complication. After discharge, she has been treated with radiation theraphy and chemotheraphy, and not recurred untill last follow-up We report a case of alveolar rhabdomyosarcoma arising to intercostal muscle, developed in 12 year-old waman, with brief review of literatures.

• The Korean Journal of Food And Nutrition
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• v.31 no.4
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• pp.457-463
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• 2018

In this study, we analyzed the protective effects of the vitamin C in the streptozotocin (STZ)-induced apoptosis using the SH-SY5Y, a neuroblastoma cell line. The cells were pretreated with the vitamin C ($100{\mu}g$) for 30 min, followed by the 24-hr treatment with the 2.5-mM STZ. The cell-viability assay using the Cell Counting Kit (CCK)-8 revealed the cell-survival rate increased by 15% following the vitamin-C pretreatment compared to the STZ-only treatment. Moreover, we conducted the western-blot analysis to determine the protective effect of the vitamin C regarding the apoptosis. Compared to those in the STZ-only-treatment group, the p-ERK and Bcl-2 expressions increased in the vitamin-C-pretreatment group, whereas the p-JNK and Bax expressions decreased. The vitamin-C pretreatment increased the expression of the SOD-1, an antioxidant enzyme, by more than 30%, indicating its protective role in the STZ-induced oxidative stress. Also, we found both the intrinsic- and extrinsic-pathway mechanisms of the STZ-induced apoptosis. The results of this study $s{\mu}ggest$ vitamin C may help prevent the neurodegenerative diseases.

• 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.

• Korean Journal of Pharmacognosy
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• v.49 no.2
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• pp.182-187
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• 2018

Many plant derived phytochemicals have been considered as the main therapeutic strategy against Alzheimer's disease (AD). AD is a progressive neurodegenerative disorder, and the most predominant cause of dementia in the elderly. Cholinergic deficit, senile plaque/${\beta}$-amyloid ($A{\beta}$) peptide deposition and oxidative stress have been identified as three main pathogenic pathways which contribute to the progression of AD. We screened many different plant species for their effective use in both modern and traditional system of medicines. In this study, we tested that MeOH extract of the stem bark of Hopea chinensis (Merr.) Hand.-Mazz. (HCM) affects on the processing of Amyloid precursor portein (APP) from the APPswe over-expressing Neuro2a cell line. We showed that HCM reduced the secretion level of $A{\beta}42$ and $A{\beta}40$ in a dose dependent manner. We found that HCM increased over 1.5 folds of the secretion level of $sAPP{\alpha}$, a metabolite of ${\alpha}$-secretase. Furthermore, we found that HCM inhibited acetylcholinesterase activity in vitro. We suggest that the stem bark of Hopea chinensis may be a useful source to develop a therapeutics for AD.

• Korean Journal of Acupuncture
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• v.23 no.3
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• pp.123-131
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• 2006

목 적 : 과산화수소는 산화적 스트레스를 통해 아폽토시스를 유도하는 것으로 알려져 있다. 본 논문에서는 과산화수소로 유발된 신경아세포종 아폽토시스 과정에서 호도약침액의 효과를 관찰하였다. 방 법 : 과산화수소로 인한 신경아세포종의 아폽토시스에서 호도약침액의 효과를 알아보기 위해 배양 중인 신경아세포종에 과산화수소를 처리하고, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MIT)분석법, 4,6-diamidino-2-phenylindole (DAPI) 염색법, reverse transcription-polymerase chain reaction (RT-PCR), western blotting의 방법으로 확인하였다. 결 과 : 과산화수소로 인한 신경아세포종의 아폽토시스에서 호도약침액을 처리한 결과, 약침액을 처리한 세포의 생존이 약 30% 정도 증가하고, 핵 응축과 단편화를 막아주며, CASP3와 BAX단백질의 발현이 감소되었다. 결 론 : 이러한 결과로 호도약침액이 과산화수소로 인한 신경아세포종의 아폽토시스과정에서 보호효과를 나타내는 것으로 사료된다.