• 생약학회지
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• 제39권3호
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• pp.213-217
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• 2008

Oxidative stress is considered to play an important role in a variety of neurodegenerative disorders of central nervous system. The immortalized mouse hippocampal cell line, HT22, phenotypically resembles neuronal precursor cells but lacks functional ionotropic glutamate receptors, thus excluding excitotoxicity as a cause for glutamate triggered cell death. Therefore, HT22 cells are a useful model for studying oxidative glutamate toxicity. In this study, we examined whether the methanol extracts of some native plants at Mt. Baekdu could protect HT22-immortalized hippocampal cells against glutamate-induced oxidative stress. Seventy-eight plants sources were collected at Mt. Baekdu, and extracted with methanol. These extracts had been screened the protective effects against glutamate-induced oxidative damage in HT22 cells at the 100 and 300 ${\mu}g/ml$. Of these, thirteen methanolic extracts, Acer mono (leaf), Artemisia stolonifera (aerial part), Carduus crispus (aerial part), Carex mongolica (whole plant), Clematis hexapetala (whole plant), Galeopsis bifida (aerial part), Galium verum (whole plant), Ganoderma lucidum (whole plant), Ixeris chinensis (whole plant), Malva verticillata (aerial part), Polygonum senticosum (whole plant), Rebes mandshricum (branch), and Taraxacum mongolicum (aerial part), showed significant protective effects against glutamate-induced oxidative damage in HT22 cells.

• 한방재활의학과학회지
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• 제18권2호
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• pp.33-43
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• 2008

Objectives : Sunghyangjungki-san(Xingxiangzhengqi-san) is a herb decoction prescribed frequently for stroke patients. The present study investigated neuroprotective effects of Sunghyangjungki-san(Xingxiangzhengqi-san) against the ischemic damage of the rat brain. Neuronal cell death under the cerebral ischemia is distinguished with the delayed cell death through apoptosis. Consequently, the effects of Sunghyangjungki-san(Xingxiangzhengqi-san) was evaluated with Bax and Bcl-2 expressions as apoptosis related factors in the brain tissues. Methods : The ischemic damage was induced by the middle cerebral artery occlusion(MCAO) method in Sprague-Dawley rats. Water extract of Sunghyangjungki-san(Xingxiangzhengqi-san) was treated for 5 days after the MCAO. Neurological scores and infarct size with TTC were measured. Bax and Bcl-2 expressions in the brain tissues were observed with immunohistochemistry. Results : Sunghyangjungki-san(Xingxiangzhengqi-san) treatment improved neurological score significantly at 5 days after the MCAO. Sunghyangjungki-san(Xingxiangzhengqi-san) treatment decreased infarct size by the MCAO, but it was not significant statistically. Sunghyangjungki-san(Xingxiangzhengqi-san) treatment attenuated Bax positive neurons significantly in the cerebral penumbra and the caudate putamen. Bcl-2 positive neurons were increased, but not significant. Sunghyangjungki-san(Xingxiangzhengqi-san) treatment increased Bcl-2/Bax expression ratios significantly in the cerebral penumbra and the caudate putamen. Conclusions : These results suggest that Sunghyangjungki-san(Xingxiangzhengqi-san) has a neuroprotective effect on the stroke with modulation of apoptosis related factors.

• 한국약용작물학회지
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• 제17권5호
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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.

• 대한본초학회지
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• 제23권3호
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• pp.1-9
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• 2008

Objectives : This research was performed to investigate protective effect of Sophora Subprostrata against transient global ischemic damage after 5-min two vessel occlusion. Methods : Gerbils were divided into three groups: Normal group, 5-min two vessel occlusion (2VO) group, Sophora Subprostrata administrated group after 2VO. The CCAs were occluded by microclip for 5min. Sophora Subprostrata was administrated orally(12mg/ml) for 7 days after 2VO. The histological and immunohistochemistrical analysis was performed at 72 hours and 7 days after the surgery each. For histological analysis, the brain tissue was stained with 1% cresyl violet solution and Immunohistochemistry for BAX and Bcl-2 was carried out to examine effect of Sophora Subprostrata on ischemic brain tissue. Results : The results showed that (1) Sophora Subprostrata has the protective effect against ischemia in CA1 area of the gerbil hippocampus 7 days after 5-minute occlusion, (2) the treatment of Sophora Subprostrata inhibits the expression of Bax relatively after 2VO-induced ischemia. That protective effect of the Sophora Subprostrata seems to be performed by regulating the proportion of Bax and Bcl-2 protein, (3) in hypoxia/reperfusion model using PC12 cell, the Sophora Subprostrata extract has the protective effect against ischemia in the dose of $2{\mu}/m{\ell}$ and $20{\mu}/m{\ell}$.This study suggests that Sophora Subprostrata has neuroprotective effect against neuronal damage following cerebral ischemia in vivo with a widely used experimental model of cerebral ischemia in Mongolian gerbils and that Sophora Subprostrata regulates the proportion of Bax and Bcl-2 protein following ischemia. And, Sophora Subprostrata extract has protective effects also on a hypoxia/reperfusion cell culture model using PC12 cell. Conclusions : Sophora Subprostrata has protective effects against ischemic brain damage at the early stage of ischemia.

• BMB Reports
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• 제49권11호
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• pp.617-622
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• 2016

Oxidative stress is closely associated with various diseases and is considered to be a major factor in ischemia. NAD(P)H: quinone oxidoreductase 1 (NQO1) protein is a known antioxidant protein that plays a protective role in various cells against oxidative stress. We therefore investigated the effects of cell permeable Tat-NQO1 protein on hippocampal HT-22 cells, and in an animal ischemia model. The Tat-NQO1 protein transduced into HT-22 cells, and significantly inhibited against hydrogen peroxide ($H_2O_2$)-induced cell death and cellular toxicities. Tat-NQO1 protein inhibited the Akt and mitogen activated protein kinases (MAPK) activation as well as caspase-3 expression levels, in $H_2O_2$ exposed HT-22 cells. Moreover, Tat-NQO1 protein transduced into the CA1 region of the hippocampus of the animal brain and drastically protected against ischemic injury. Our results indicate that Tat-NQO1 protein exerts protection against neuronal cell death induced by oxidative stress, suggesting that Tat-NQO1 protein may potentially provide a therapeutic agent for neuronal diseases.

• 한국약용작물학회지
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• 제14권2호
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• pp.70-76
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• 2006

Paeoniae radix has been widely used for its anti-allergic, anti-inflammatory and analgesic effects, and demonstrated to have anticonvulsant, memory enhancing and anxiolytic activities. The present study was performed to examine the protective effect of methanol extract of Paeoniae radix (PR) from Paeoniae Japonica Miyabe et Takeda (Paeoniaceae) on hydrogen peroxide $(H_2O_2)-induced$ neurotoxicity using cultured rat cerebral cortical neuron. $H_2O_2$ produced a concentration-dependent reduction of neuronal viability, PR, over a concentration range of 10 to $100\;{\mu}g/ml$ showed concentration-dependent decrease of the $H_2O_2$$(100\;{\mu}M)-induced$ neuronal cell death, as assessed by a 3-[4,5-dimethylthiazol-2-yl]-2,5-di-phenyl-tetrazolium bromide assay and the number of apoptotic nuclei, evidenced by Hoechst 33342 staining. PR $(100\;{\mu}g/ml$ inhibited $100\;{\mu}M$ $H_2O_2-induced$ elevation of the cytosolic $Ca^{2+}$ concentration $([Ca^{2+}]_c)$, which was measured by a fluorescent dye, flue-4 AM. PR $(50\;{\mu}g/ml$ inhibited glutamate release into medium induced by $100\;{\mu}M$ $H_2O_2$, which was measured by HPLC, and generation of reactive oxygen species (ROS). These results suggest that PR may mitigate the $H_2O_2-induced$ neurotoxiciy by interfering with the increase of $[Ca^{2+}]_c$, and then inhibiting glutamate release and generation of ROS in cultured neurons.

• 동의신경정신과학회지
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• 제20권1호
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• pp.235-247
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• 2009

Objectives : Ginseng Radix Rubra water extract(RGE) has been used in vivo test for its beneficial effects on neuronal survival and neuroprotective functions, particularly in connection with APP-related dementias and Alzheimer's disease (AD). APP derived from proteolytic processing of the ${\beta}$-amyloid precursor protein (APP), including the amyloid-${\beta}$ peptide (A${\beta}$), plays a critical role in the pathogenesis of Alzheimer's dementia. Methods : We determined that RGE inhibits formation of APP, which are the behavior, and possibly causative, feature of AD. Results and Conclusions : In the cells, RGE significantly activated antiapoptosis and decreased the activity of APP-grim, a key enzyme in the apoptosis cell-signaling cascade. These results suggest that neuronal damage in AD might be due to two factors: a direct APP toxicity and multiple cellular and molecular neuroprotective mechanisms, including attenuation of apoptosis and direct inhibition of APP, underlie the neuroprotective effects of RGE.

• Journal of Applied Biological Chemistry
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• 제62권4호
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• pp.347-353
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• 2019

Stings of jellyfish, which frequently occur in a warm season, cause severe pain, inflammation and sometimes irreversible results such as the death. Harmful venoms from jellyfish, therefore, have been studied for finding the therapeutic agents to relieve pain or to neutralize toxic components. However, it is still unclear if and how jellyfish venom reveal neuronal toxicity even though pain induction seems to result from the activation of nociceptors such as nerve endings. In this study, using HT-22 cell line, we investigated neurotoxic effects of the venom of Chrysaora pacifica (CpV) which appears in South-East ocean of Korea. In 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, CpV significantly reduced the viability of HT-22 cells in a dose-dependent manner. Additionally, in 2',7'-Dichlorofluorescin diacetate fluorescence test under the culture condition lacking dominant inflammatory factors, CpV remarkably increased the production of intracellular reactive oxygen species (ROS). Reduced responsive fluorescence to Rhodamine123 and increased expression of intracellular cytochrome c were also observed in HT-22 cells treated with CpV. These indicate that CpV-reduced viability of HT-22 cells may be due to the activation of apoptotic signalings mediated with oxidative stress and mitochondrial dysfunction. Furthermore, removing Ca²⁺ ion or adding N-acetyl-Lcystein remarkably blocked the CpV effect to reduce the viability of HT-22 cells. The findings in this study clearly demonstrate that CpV may activate Ca²⁺-mediated ROS signalings and mitochondrial dysfunction resulting in neuronal damage or death, and suggest that blocking Ca²⁺ pathway is a therapeutic approach to possibly block toxic effects of jellyfish venoms.

• Nuclear Medicine and Molecular Imaging
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• 제41권2호
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• pp.141-151
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• 2007

파킨슨병은 노년층에 가장 흔한 퇴행성 뇌질환 중의 하나로 진행성핵상마비, 다중계 위축, 루이체 치매 등과 같은 비전형 파킨슨병과 임상적으로 감별이 어려울 수 있다. 파킨슨병과 비전형 파킨슨병의 감별은 치료방침 결정과 예후평가뿐만 아니라 파킨슨병의 원인과 병태생리를 연구하고 새로운 치료법 개발에 있어서도 매우 중요하다. 파킨슨병과 비전형 파킨슨병과 같이 파킨슨 증후군을 유발하는 질환은 선조체내 도파민 신경의 퇴행성 변화를 흔히 동반하지만 병태생리학적으로 서로 다른 뇌피질 및 피질하 구조물에서의 신경세포 소실을 동반하고 있다. 따라서 국소 시냅스 활성도와 신경 및 시냅스의 손상, 그리고 원발병변과 기능적으로 연결된 원격부위의 기능이상 등을 대변하는 뇌포도당 대사를 F-18FDG PET으로 평가하는 것은 파킨슨 병의 감별진단과 병태생리를 평가하는데 유용하다.

• Journal of Microbiology and Biotechnology
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• 제31권4호
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• pp.584-591
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• 2021

Marine algae (seaweed) encompass numerous groups of multicellular organisms with various shapes, sizes, and colors, and serve as important sources of natural bioactive substances. The brown alga Ecklonia cava Kjellman, an edible seaweed, contains many bioactives such as phlorotannins and fucoidans. Here, we evaluated the antioxidative, neuroprotective, and anti-apoptotic effects of E. cava extract (ECE), E. cava phlorotannin-rich extract (ECPE), and the phlorotannin dieckol on neuronal PC-12 cells. The antioxidant capacities of ECPE and ECE were 1,711.5 and 1,050.4 mg vitamin C equivalents/g in the ABTS assay and 704.0 and 474.6 mg vitamin C equivalents/g in the DPPH assay, respectively. The dieckol content of ECPE (58.99 mg/g) was approximately 60% higher than that of ECE (36.97 mg/g). Treatment of PC-12 cells with ECPE and ECE increased cell viability in a dose-dependent manner. Intracellular oxidative stress in PC-12 cells due to ECPE and ECE decreased dose-independently by up to 63% and 47%, respectively, compared with the stress control (323%). ECPE reduced the production of the pro-apoptotic proteins Bax and caspase-3 more effectively than ECE. Early and late apoptosis in PC-12 cells were more effectively decreased by ECPE than ECE treatments. From the results obtained in this study, we concluded that ECPE, which is rich in phlorotannins, including the marker compound dieckol, may be applied to the development of functional materials for improving cognition and memory.