• 대한의생명과학회지
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• 제15권3호
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• pp.261-263
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• 2009

Methylprednisolone is a synthetic glucocorticoid which is usually taken intravenously for many neurosurgical diseases which cause edema including brain tumor, and trauma including spinal cord injury. Methylprednisolone reduces swelling and decreases the body's immune response. It is also used to treat many immune and allergic disorders, such as arthritis, lupus, psoriasis, asthma, ulcerative colitis, and Crohn's disease. To identify genes expressed during methylprednisolone treatment against neurons of rats (PC12 cells), DNA microarray method was used. We have isolated 2 gene groups (up- or down-regulated genes) which are methylprednisolone differentially expressed in neurons. Lipocalin 3 is the gene most significantly increased among 772 up-regulated genes (more than 2 fold over-expression) and Aristaless 3 is the gene most dramatically decreased among 959 down-regulated genes (more than 2 fold down-expression). The gene increased expression of Fgb, Thbd, Cfi, F3, Kngl, Serpinel, C3, Tnfrsf4 and Il8rb are involved stress-response gene, and Nfkbia, Casp7, Pik3rl, I11b, Unc5a, Tgfb2, Kitl and Fgf15 are strongly associated with development. Cell cycle associated genes (Mcm6, Ccnb2, Plk1, Ccnd1, E2f1, Cdc2a, Tgfa, Dusp6, Id3) and cell proliferation associated genes (Ccl2, Tnfsf13, Csf2, Kit, Pim1, Nr3c1, Chrm4, Fosl1, Spp1) are down-regulated more than 2 times by methylprednisolone treatment. Among the genes described above, 4 up-regulated genes are confirmed those expression by RT-PCR. We found that methylprednisolone is related to expression of many genes associated with stress response, development, cell cycle, and cell proliferation by DNA microarray analysis. However, We think further experimental molecular studies will be needed to figure out the exact biological function of various genes described above and the physiological change of neuronal cells by methylprednisolone. The resulting data will give the one of the good clues for understanding of methylprednisolone under molecular level in the neurons.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2001년도 추계학술대회 및 정기총회
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• pp.85-85
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• 2001

Sam-Hwang-Sa-Shim-Tang(SHSST), a traditional Chinese medicine, composed of Rhei rhizoma, Scutellaria radix, and Coptidis rhizoma were used in the several disease including hypertension, constipation, and hemorrhage. In the present study, we investigated the neuroprotective effects of SHSST and its ingredients on the ischemia/ reperfusion-induced brain injury was evaluated in the rat brain. Ischemia was induced by intraluminal occlusion of the right middle cerebral artery for 120 min and reperfusion was continued for 22 h. SHSST (450 mg/kg), Rhei rhii oma (100 mg/kg), Coptidis rhizoma (100 mg/kg), and Scutellaria radik (100 mg/kg) were orally administered twice, promptly prior to reperfusion and 2 h after the repefusion. Total infarction volume in the ipsilateral hemisphere of ischemia/ reperfusion rats was significantly lowed by the treatments of SHSST (39.2%) and Scutellaria radix (66.5%). However, Coptidis rhizoma did not show any significant effects on the total infarct volume. The inhibiting effect of Scutellaria radix on the total infarct volume was more potent than that of SHSST. In addition, Scutellaria radix significantly inhibited myeloperoxidase (MPO) activity, an index of neutrophil infiltration in ischemic brain tissue. However, there was marked mismatch between total infarct volume and MPO activity in the Scutellaria radix-treated rats. Our findings suggest that Scutellaria radix as an ingredient of SHSST plays a protective role in ischemia-induced brain injury by inhibiting neutrophil infiltration. The effects of Rhei rhizoma on transient brain ischemia-induced neuronal injury are under study.

• Journal of Applied Biological Chemistry
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• 제63권2호
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• pp.137-145
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• 2020

Oxidative stress is one of the pathogenic mechanisms of various neurodegenerative diseases, such as Alzheimer's disease. Neuroglia, the most abundant cells in the brain, is thought to play an important role in the antioxidant defense system and neuronal metabolic support against neurotoxicity and oxidative stress. We investigated the protective effect of paeoniflorin (PF) against oxidative stress in C6 glial cells. Exposure of C6 glial cells to hydrogen peroxide (H₂O₂, 500 μM) significantly decreased cell viability and increased amounts of lactate dehydrogenase (LDH) release, indicating H₂O₂-induced cellular damage. However, treatment with PF significantly attenuated H₂O₂-induced cell death as shown by increased cell survival and decreased LDH release. The H₂O₂-stimulated reactive oxygen species production was also suppressed, and it may be associated with improvement of superoxide dismutase activity by treatment with PF. In addition, an increase in ratio of Bcl-2/Bax protein expression was observed after treatment with PF. In particular, the down-stream of the apoptotic signaling pathway was inhibited in the presence of PF, mostly by reduction of cleaved-poly ADP ribose polymerase, cleaved caspase-3, and -9 protein expression. Furthermore, H₂O₂-induced phosphorylation of c-Jun N-terminal kinase and extracellular signal-regulated kinase 1/2 was attenuated by treatment with PF. Taken together, neuroprotective effect of PF against oxidative stress probably result from the regulation of apoptotic pathway in C6 glial cells. In conclusion, our findings suggest that PF may be a potent therapeutic agent for neurodegenerative disorders.

• 생명과학회지
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• 제23권1호
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• pp.125-130
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• 2013

Calponin 3는 F-actin과 결합하는 단백질로 신경계의 가소성과 시냅스 활성을 조절하는데 중요한 역할을 하는 것으로 알려져 있다. 평활근과 심장근에 발현되는 calponin 1과 calponin 2와는 다르게 calponin 3는 뇌 조직에 많이 발현되어 있는 것으로 보고되고 있다. 본 연구는 마우스에서 3-nitropropionic acid를 투여하여 선조체에 비가역적 신경 손상을 주었을 때 calponin 3의 발현 양상을 알아보기 위하여 진행되었다. 본 연구 결과 3-nitropropionic acid를 마우스에 투여하였을 때 선조체에서 신경조직의 괴사가 일어남을 관찰하였으며 calponin 3는 약물 투여 후 1.5일부터 서서히 발현되는 것을 확인하였다. 특히, calponin 3는 신경조직의 괴사가 일어나는 부위의 주변부에서 발현되는 것을 확인하였으며 형광 이중면역 염색법으로 확인한 결과 GFAP를 발현하는 별아교세포에서 발현됨을 최초로 밝혔다. 따라서, calponin 3가 3-nitropropionic acid의 독성에 저항성을 나타내는 부위에서 별아교세포에서만 특이적으로 발현되는 것으로 보아 calponin 3는 별아교세포에 의한 신경아교증에 중요한 역할을 하는 것으로 추측된다.

• 한국시뮬레이션학회논문지
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• 제17권4호
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• pp.167-174
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• 2008

공초점 현미경(confocal microscopy) 기술의 적용은 살아있는 세포를 고배율로 관찰하는 것을 가능하게 하였다. 알츠하이머나 파킨슨 질환 같은 퇴행성 뇌질환의 경우 뇌세포의 수상돌기의 형태학적 변화가 연관되어 있음이 알려져 있다. 따라서 공초점 현미경 영상으로부터 이러한 정보를 추출하는 방법에 대한 연구가 필요하다. 그러나 공초점 현미경 영상은 명암도 분포가 고르지 않고, 구조의 경계 부분의 번짐 현상 등으로 인해 구조 추출에 어려움을 겪고 있는 실정이다. 따라서 이러한 문제를 극복하고 관심 구조에 대한 특성을 추출할 수 있는 영상처리 기법이 필요하다. 본 논문에서는 뇌세포의 수상돌기 공초점 현미경 사진으로부터 구조정보를 추출하는 새로운 방법을 제안한다. 첫째, 미세 분기 구조의 경계를 향상시키는 비선형 확산 필터링을 적용한다. 둘째, 관심구조를 반복적 역치 선택 방법을 이용해 분할한다. 셋째, 분할된 구조의 분석을 위해 구조의 중심축과 경계선을 추출하기 위한 패스트 마칭 방법(Fast Marching Method)에 기반을 둔 골격화를 수행한다. 본 논문에서 제안된 방법은 기존의 방법들과는 달리 주변 잡음에 덜 민감하였으며 거친 경계선에 영향을 훨씬 적게 받음으로써 보다 정확하고 사실적인 중심축 추출 결과를 보였다.

• 약학회지
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• 제60권2호
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• pp.92-99
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• 2016

Parkinson's disease (PD) is one of the representative neurodegenerative movement disorders with the selective loss of dopaminergic neurons in the substantia nigra. 6-Hydroxydopamine (6-OHDA) is widely used as an experimental model system to mimic PD and has been reported to cause neuronal cell death via oxidative and/or nitrosative stress. Therefore, daily intake of dietary or medicinal plants which fortifies cellular antioxidant capacity can exert neuroprotective effects in PD. In the present study, we have investigated the protective effect of Korean red ginseng (KRG) against 6-OHDA-induced nitrosative death in C6 glioma cells. Treatment of C6 cells with 6-OHDA decreased cell viability and increased expression of inducible nitric oxide synthase, production of nitric oxide as well as peroxynitrite, and formation of nitrotyrosine. 6-OHDA led to apoptotic cell death as determined by decreased Bcl-2/Bax, phosphorylation of JNK, activation of caspase-3, and cleavage of PARP. Conversely, pretreatment of C6 cells with KRG attenuated 6-ODHA-induced cytotoxicity, apoptosis, and nitrosative damages. To further elucidate the molecular mechanism of KRG protection against 6-OHDA-induced nitrosative cell death, we have focused on the cellular self-defense molecules against exogenous noxious stimuli. KRG treatment up-regulated heme oxygenase-1 (HO-1), a key antioxidant enzyme essential for cellular defense against oxidative and/or nitrosative stress via activation of Nrf2. Taken together, these findings suggest KRG may have preventive and/or therapeutic potentials for the management of PD.

• Journal of Ginseng Research
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• 제44권4호
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• pp.603-610
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• 2020

Background: Depression is a common neuropsychiatric disease that shows astrocyte pathology. Ginsenoside Rf (G-Rf) is a saponin found in Panax ginseng which has been used to treat neuropsychiatric diseases. We aimed to investigate antidepressant properties of G-Rf when introduced into the L-alphaaminoadipic acid (L-AAA)-infused mice model which is representative of a major depressive disorder that features diminished astrocytes in the brain. Methods: L-AAA was infused into the prefrontal cortex (PFC) of mice to induce decrease of astrocytes. Mice were orally administered G-Rf (20 mg/kg) as well as vehicle only or imipramine (20 mg/kg) as controls. Depression-like behavior of mice was evaluated using forced swimming test (FST) and tail suspension test (TST). We observed recovery of astroglial impairment and increased proliferative cells in the PFC and its accompanied change in the hippocampus by Western blot and immunohistochemistry to assess the effect of G-Rf. Results: After injection of L-AAA into the PFC, mice showed increased immobility time in FST and TST and loss of astrocytes without significant neuronal change in the PFC. G-Rf-treated mice displayed significantly more decreased immobility time in FST and TST than did vehicle-treated mice, and their immobility time almost recovered to those of the sham mice and imipramine-treated mice. G-Rf upregulated glial fibrillary acidic protein (GFAP) expression and Ki-67 expression in the PFC reduced by L-AAA and also alleviated astroglial change in the hippocampus. Conclusion: G-Rf markedly reversed depression-like behavioral changes and exhibited protective effect against the astrocyte ablation in the PFC induced by L-AAA. These protective properties suggest that G-Rf might be a therapeutic agent for major depressive disorders.

• 혜화의학회지
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• 제26권1호
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• pp.1-10
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• 2017

Objectives: The aim of this study is (1) to investigate the historic changes and pharmacological efficacies of Woohwangchungsim-won and (2) to discuss the necessities for Woohwangchungsim-won's clinical applications. Methods: This study was performed through (1) investigating the ancient literature records related with Woohwangchungsim-won and analyzing Woohwangchungsim-won's composition, dosage and indications, (2) searching articles about Woohwangchungsim-won on 10 major Korean web and 3 major foreign web article search engines and analyzing Woohwangchungsim-won's pharmacological efficacies and indications. Results: Woohwangchungsim-wom has been used for cerebrovascular diseases such as stroke and palpitation. Also, there are some ancient literature records of Woohwangchungsim-won's clinical applications in neuropsychiatric disorders such as depression and bipolar disorder. In addition, there have been a number of experimental studies which demonstrate Woohwangchungsim-won's neuroprotective effect on cerebral cortex and hippocampus injury. So, it is possible to infer that Woohwangchungsim-won can be used for the treatments of neuropsychiatric disorders associated with neuronal cell death in cerebral cortex and hippocampus. But there have been no or less experimental studies which demonstrate the pharmacological efficacy of Woohwangchungsim-won on such disease. Conclusion: It is necessary that further experimental studies which demonstrate Woohwangchungsim-won's pharmacological efficacy on neuropsychiatric disorders should be done and Woohwangchungsim-won's clinical applications should be expanded on the basis of those related experimental results.

• 한국식품영양과학회지
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• 제40권8호
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• pp.1107-1112
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• 2011

본 연구는 기존에 알코올 해독 기능이 우수한 것으로 알려진 헛개나무 열매 추출물과 헛개나무 열매 추출물을 주성분으로 하여 매실 및 댕댕이나무 열매 추출물이 혼합되어진 새로운 식품 조성물의 항알코올 기능에 대한 효능을 비교 분석함으로써 새로운 알코올 독성 경감 소재를 개발하고자 하였다. 새로운 식품 조성물인 SAC-1을 흰쥐에게 투여한 후 알코올을 섭취시켰을 때 혈중 알코올 농노의 저하가 헛개나무 추출물에 비하여 매우 우수한 효능이 있는 것으로 나타났으며, 간손상의 지표인 GOT, GPT에 있어서 대조군에 비하여 낮은 값을 나타내어 알코올에 의한 간손상을 경감시킬 수 있는 것으로 생각된다. 또한, 조직에서 산화적 손상으로 효능을 살펴본 결과는 지질과산화물의 생성을 혈장과 간 조직에서 모두 억제하는 것으로 나타났으며, total glutathione의 감소를 억제하는 것으로 나타나 SAC-1은 알코올성 조직 손상에서 충분한 보호 작용을 나타낼 수 있었던 것으로 생각된다. 특히 SAC-1은 헛개나무 열매 추출물 단독 사용에 비해서 더 높은 활성을 나타낸 것으로 나타났으며, 이것은 SAC-1이 알코올 해독에 좋은 천연 성분을 함유하고 있는 결과로 추측된다. 이상의 결과에서 SAC-1은 알코올로 인해 유도되어지는 조직 손상 및 숙취 증상으로부터 조직을 보호할 수 있는 능력이 있는 것으로 생각된다.

• 생약학회지
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• 제41권3호
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• pp.166-173
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• 2010

Oxidative stress to proteins, lipids, or DNA is higher in human autopsy tissue and in rodent models of a number of neurodegenerative conditions, including Alzheimer's and Parkinson's disease. On the basis of this information, we established a screening system using N18-RE-105 cells to identify therapeutic agents that can protect cells from glutamate toxicity. During the course of our screening program, we recently isolated the active compound 9-hydroxy-$\alpha$-tocopherone ($\alpha$-TP), which prevents glutamate-induced cell death, from Viola mandshurica. The chemical structure of $\alpha$-TP was identified using spectroscopic methods and by comparison with literature values. Antioxidant activity and protective effects of $\alpha$-TP were evaluated by DPPH radical-scavenging assay, morphological assay, MTT reduction assay, and lactate dehydrogenase (LDH) release assay. These results suggest that $\alpha$-TP could be a new potential chemotherapeutic agent against neuronal diseases.