• 동의생리병리학회지
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• 제23권4호
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• pp.818-824
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• 2009

This study aimed to evaluate the effect of purgation therapy with Natrii sulfas, a therapy for stroke patients with constipation in the oriental medicine, on the ischemic brain damage of the rats. The ischemic brain damage was induced by the middle cerebral artery occlusion (MCAO), Natrii sulafas was administered once after the MCAO. After 48 hours, expressions of Bax, Bcl-2, c-Fos, and HSP72 on the brain tissues were observed by immunohistochemistrical methods or technique. Purgation therapy with Natrii sulfas attenuated the excess of Bax expression caused by the ischemic brain damage. It was significant statistically in the penumbra of cerebral cortex, but not in the caudate putamen, of the MCAO rats. Purgation therapy with Natrii sulfas did not attenuate the excess of Bcl-2 expression caused by the ischemic brain damage. Purgation therapy with Natrii sulfas did not attenuate the excess of c-Fos expression caused by the ischemic brain damage. Purgation therapy with Natrii sulfas attenuated the excess of HSP72 expression caused by the ischemic brain damage. It was significant statistically in the penumbra of cerebral cortex, but not in the caudate putamen, of the MCAO rats. These results suggest that purgation therapy with Natrii sulfas has a neuroprotective effect on the ischemic brain damage and an anti-apoptotic effect.

• Journal of Korean Neurosurgical Society
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• 제52권6호
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• pp.509-512
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• 2012

Objective : The purpose of this study is to evaluate neuroprotective effect of sacral neuromodulation in rat spinal cord injury (SCI) model in the histological and functional aspects. Methods : Twenty-one female Sprague Dawley rats were randomly divided into 3 groups : the normal control group (CTL, n=7), the SCI with sham stimulation group (SCI, n=7), and the SCI with electrical stimulation (SCI+ES, n=7). Spinal cord was injured by dropping an impactor from 25 mm height. Sacral nerve electrical stimulation was performed by the following protocol : pulse duration, 0.1 ms; frequency, 20 Hz; stimulation time, 30 minutes; and stimulation duration, 4 weeks. Both locomotor function and histological examination were evaluated as scheduled. Results : The number of anterior horn cell was $12.3{\pm}5.7$ cells/high power field (HPF) in the CTL group, $7.8{\pm}4.9$ cells/HPF in the SCI group, and $6.9{\pm}5.5$ cells/HPF in the SCI+ES group, respectively. Both the SCI and the SCI+ES groups showed severe loss of anterior horn cells and myelin fibers compared with the CTL group. Cavitation and demyelinization of the nerve fibers has no significant difference between the SCI group and the SCI+ES group. Cavitation of dorsal column was more evident in only two rats of SCI group than the SCI+ES group. The locomotor function of all rats improved over time but there was no significant difference at any point in time between the SCI and the SCI+ES group. Conclusion : In a rat thoracic spinal cord contusion model, we observed that sacral neuromodulation did not prevent SCI-induced myelin loss and apoptosis.

• 한국산학기술학회논문지
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• 제18권12호
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• pp.521-528
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• 2017

과도한 음주는 치매 및 알츠하이머 병과 같은 여러 신경계 질환을 일으키는 주요원인 중 하나로 알려져 있으며 이를 해결하기 위한 많은 노력인 진행 중이다. 또한, 홍삼은 신경 세포의 생존, 세포 자멸사의 억제 및 신경 세포의 신경 재생을 향상시키는 것으로 알려져 있다. 본 연구의 목적은 Rg3 풍부 고려홍삼 추출액(KRG)이 알코올 유발성 신경독성으로 인하여 일어나는 PC12 세포의 세포 사멸을 억제 할 수 있는지, 그리고 KRG가 caspase 매개 경로와 관련된 몇 가지 인자들을 어떻게 조절하는지 확인하는 것이다. 그 방법으로, 우리는 PC12 세포에서의 세포 생존율과 세포 사멸율은 EZ-Cytox 세포 생존율 측정 kit와 유세포 분석기로 측정하였고, 세포 자멸 관련 단백질(Bcl-2, Bax, caspase-3)의 발현 정도를 Western blot기법으로 측정하였으며, 측정된 결과의 유의성을 ANOVA 분석법으로 확인하였다. 그 결과, KRG는 Bcl-2의 발현을 증가시키고, Bid와 Bax 및 caspase-3 발현을 저해하였고, 이를 통해 알코올로 유도된 PC12 세포의 세포 사멸을 억제하였다. 이러한 결과를 통해, KRG에 의해 유도된 Bcl-2 발현의 증가와 Bid 및 Bax 발현의 하향 조절이 caspase-3 발현을 하향 조절하고, 결국 미토콘드리아 세포 사멸 경로를 억제한다는 것을 결론내릴 수 있었다. 본 연구는 향 후, KRG가 신경 보호제 후보로서 개발할 가치가 있음을 제시하였다.

• 한국식품과학회지
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• 제49권5호
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• pp.538-543
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• 2017

본 연구에서는 떫은 감인 청도반시(Diospyros kaki Thunb. cv. Cheongdo-Bansi)를 탈삽하여 곶감으로 만드는 과정 중에 다량의 부산물로 생겨나는 감 껍질을 활용하고자 산화방지능 및 신경세포 보호능을 평가하였다. 탈삽한 감 껍질을 40% (v/v) 에탄올-물혼합용액을 사용하여 초음파 추출을 한 후에, 가열처리와 비가열처리 방법을 이용하여 각각의 추출물을 확보하였다. 가열처리한 추출물이 비가열처리로 얻어진 것에 비해서 총페놀 함량, 총플라보노이드 함량, 산화방지능에서 약 1.3-1.8배 더 높았다. 비가열처리 추출물과 비교하여, 가열처리한 것이 PC-12 신경세포의 생존율 더 높이고, 세포 내 산화스트레스를 좀 더 완화하였다. AChE와 BChE 억제능 역시 가열처리한 추출물이 비가열처리로 얻은 추출물보다 더 높았다. 이러한 결과들은 산화방지능을 보유하며 콜린가수분해효소를 억제하는 기능성 소재 발굴을 위한 탈삽 감껍질 추출물 활용 가능성을 보여준다.

• The Korean Journal of Physiology and Pharmacology
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• 제19권3호
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• pp.219-228
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• 2015

Excessive microglial activation and subsequent neuroinflammation lead to synaptic loss and dysfunction as well as neuronal cell death, which are involved in the pathogenesis and progression of several neurodegenerative diseases. Thus, the regulation of microglial activation has been evaluated as effective therapeutic strategies. Although dieckol (DEK), one of the phlorotannins isolated from marine brown alga Ecklonia cava, has been previously reported to inhibit microglial activation, the molecular mechanism is still unclear. Therefore, we investigated here molecular mechanism of DEK via extracellular signal-regulated kinase (ERK), Akt and nicotinamide adenine dinuclelotide phosphate (NADPH) oxidase-mediated pathways. In addition, the neuroprotective mechanism of DEK was investigated in microglia-mediated neurotoxicity models such as neuron-microglia co-culture and microglial conditioned media system. Our results demonstrated that treatment of anti-oxidant DEK potently suppressed phosphorylation of ERK in lipopolysaccharide (LPS, $1{\mu}g/ml$)-stimulated BV-2 microglia. In addition, DEK markedly attenuated Akt phosphorylation and increased expression of $gp91^{phox}$, which is the catalytic component of NADPH oxidase complex responsible for microglial reactive oxygen species (ROS) generation. Finally, DEK significantly attenuated neuronal cell death that is induced by treatment of microglial conditioned media containing neurotoxic secretary molecules. These neuroprotective effects of DEK were also confirmed in a neuron-microglia co-culture system using enhanced green fluorescent protein (EGFP)-transfected B35 neuroblastoma cell line. Taken together, these results suggest that DEK suppresses excessive microglial activation and microglia-mediated neuronal cell death via downregulation of ERK, Akt and NADPH oxidase-mediated pathways.

• 생명과학회지
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• 제20권7호
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• pp.1121-1126
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• 2010

활성산소에 의해 유도되는 산화적 스트레스가 노화와 관련된 각종 퇴행성 신경질환의 원인으로 밝혀짐에 따라 본 연구에서는 활성산소종인 $H_2O_2$가 유도하는 강력한 산화적 스트레스로부터 신경세포를 보호하는 물질을 탐색하기 위하여 하고초 추출물(PSE)에 관하여 연구하였다. PC12 세포를 이용하여 MTT reduction assay, LDH release assay 및 colony formation assay 등 여러 가지 생물학적인 assay를 통하여 PSE의 세포 보호효과를 확인하였다. 그리고 광학 현미경을 이용한 형태학적 변화 관찰에서도 $H_2O_2$ 처리군에 비해 높은 세포 보호효과를 확인할 수 있었으며, Hoechst 33342 염색과 세포주기 분석을 통하여 PSE의 높은 apoptosis 억제효과를 확인할 수 있었다. 이상의 결과로부터 하고초는 $H_2O_2$에 의해 유도된 세포독성으로부터 PC12 세포손상을 강력하게 억제하는 효과가 있다는 것을 확인할 수 있었으며, 퇴행성 신경질환에 대한 새로운 치료제로서의 가능성을 제시하였다.

• Journal of Ginseng Research
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• 제46권4호
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• pp.515-525
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• 2022

Background: The incidence of ischemic cerebrovascular disease is increasing in recent years and has been one of the leading causes of neurological dysfunction and death. Ginsenoside Rg1 has been found to protect against neuronal damage in many neurodegenerative diseases. However, the effect and mechanism by which Rg1 protects against cerebral ischemia-reperfusion injury (CIRI) are not fully understood. Here, we report the neuroprotective effects of Rg1 treatment on CIRI and its possible mechanisms in mice. Methods: A bilateral common carotid artery ligation was used to establish a chronic CIRI model in mice. HT22 cells were treated with Rg1 after OGD/R to study its effect on [Ca²⁺]_i. The open-field test and poleclimbing experiment were used to detect behavioral injury. The laser speckle blood flowmeter was used to measure brain blood flow. The Nissl and H&E staining were used to examine the neuronal damage. The Western blotting was used to examine MAP2, PSD95, Tau, p-Tau, NOX2, PLC, p-PLC, CN, NFAT1, and NLRP1 expression. Calcium imaging was used to test the level of [Ca²⁺]_i. Results: Rg1 treatment significantly improved cerebral blood flow, locomotion, and limb coordination, reduced ROS production, increased MAP2 and PSD95 expression, and decreased p-Tau, NOX2, p-PLC, CN, NFAT1, and NLRP1 expression. Calcium imaging results showed that Rg1 could inhibit calcium overload and resist the imbalance of calcium homeostasis after OGD/R in HT22 cells. Conclusion: Rg1 plays a neuroprotective role in attenuating CIRI by inhibiting oxidative stress, calcium overload, and neuroinflammation.

• 생명과학회지
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• 제32권10호
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• pp.771-777
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• 2022

파킨슨병에서의 도파민 신경세포의 사멸 원인은 다양하며 별개의 유전적 요소와 환경적 요소들이 관여한다. 드물게 발생하는 유전성 파킨슨병에서 parkin의 돌연변이와 기능 상실은 주로 소포체 스트레스를 통해 중뇌 흑질의 도파민 신경세포를 특이적으로 손상시킨다. 상대적으로 일반적인 특발성 파킨슨병에서는 살충제 노출이 역학적으로 중요하다. 그러나 환경독성물질에의 노출과 유전성 파킨슨병의 연관성에 대해서는 잘 알려진 바가 없다. 본 연구에서는 잘 확립된 중뇌 유래의 도파민 신경세포주인 N27-A를 사용하여 특발성 파킨슨병과 유전성 파킨슨병 사이의 공통된 발병 기작의 증거를 확인하였다. 특발성 파킨슨병을 유발하는 유기염소계 살충제인 디엘드린은 BiP/Grp78, 헴산화효소-1과 같은 소포체 스트레스 반응 표지자를 발현 유도하였고, 특히 parkin 단백질의 발현을 증가시켰다. 디엘드린이 N27-A 세포를 사멸시키는 과정에서 소포체 스트레스 특이적 세포사를 매개하는 Caspase-12의 활성화가 유의미하게 증가하였다. 흥미롭게도 디엘드린에 의한 N27-A 세포의 사멸이 소포체 단백질인 parkin과 Bcl-2의 과발현시 유의미하게 억제되었다. 본 연구 결과, 소포체 스트레스의 누적이 특발성, 유전성 파킨슨병의 공통의 발병 기작일 가능성이 있으며, 몇 가지 소포체 관련 단백질들이 디엘드린에 의한 도파민 신경세포 손상으로부터 보호 효과를 가지는 것으로 보인다.

• 동의생리병리학회지
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• 제16권5호
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• pp.928-931
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• 2002

To elucidate the toxic effect of oxygen free radicals on cultured mouse cerebral neurons damaged by hydrogen peroxide(H₂O₂)-induced neurotoxicity, we examined the neurotoxicity induced by oxygen radicals by NR assay when cultured cerebral neurons were grown in the media containing various concentrations of H202 for 6 hours. In addition, neuroprotective effects of herb extracts such Rhizoma Gastrodiae(RG) on H202-induced neurotoxicity in cultured cerebral neurons were evaluated after cultured cerebral neurons were preincubated with various concentrations of herb extract, RG for 2 hours before 50uM H₂O₂ for 6 hours. H₂O₂ decreased remarkably cell viability in dose-and time-dependent manner in these cultures, and also herb exract, RG decreased LDH activity of cerebral neurons damaged by H₂O₂. From the above results, it is suggested that H₂O₂ was toxic in cultured cerebral neurons from mouse, and RG was effective in blocking the neurotoxicity induced by oxygen radicals in these cultures.

• 동의생리병리학회지
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• 제17권6호
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• pp.1433-1440
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• 2003

This research was performed to investigate protective effect of Sophorae subprostratae Radix and each fractions against ischemic damage using PC12 cells. To observe the protective effect of Sophorae subprostratae Radix on ischemia damage, vibility and changes in activities of Superoxide dismutase (SOD), Glutathione Peroxidase (GPx), Catalase and Production of Malondialdehyde (MDA) were observed after treating PC12 cells with Sophorae subprostratae Radix during ischemic insult. Groups were divided into five groups: no treated (Normal), hypoxia chamber for 48hrs followed by 6h at normoxic chamber (H/R), Sop horae subprostratae Radix total phase treated group with H/R (Total), Sophorae subprostratae Radix water phase treated group with H/R (Water), Sophorae subprostratae Radix BuOH phase treated group with H/R (BuOH), Sophorae subprostratae Radix alkaloid phase treated group with H/R (Alkaloid). The results showed that (1) in hypoxiajreperfusion model using PC12 cell, the Sophorae subprostratae Radix has the protective effect against ischemia in the dose of 0.2 ㎍/㎖, 2 ㎍/㎖ and 20 ㎍/㎖, (2) Sophorae subprostratae Radix increased the activities of glutathione peroxidase and catalase. (3) the activity of Superoxide Diamutase(SOD) increased by ischemic damage, which might represent the self protection. This study suggests that Sophorae subprostratae Radix has neuroprotective effect against neuronal damage following hypoxiajreperfusion cell culture model using PC12 cell and dose dependency effects. In conclusion, Sophorae subprostratae Radix has protective effects against ischemic oxidative damage at the early stage of ischemia.