• 대한유전성대사질환학회지
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• 제20권1호
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• pp.1-13
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• 2020

Gaucher disease (GD)는 glucocerebrosidase 유전자(GBA)의 돌연변이에 의하여 발병하는 전세계적으로 가장 유병율이 높은 리소좀 축적질환이다. GD는 신경학적인 증상의 유무에 따라 3가지 임상형으로 구분된다. 신경병증 GD인 2형과 3형의 경우는 대뇌에서 glucosylceramide (GlcCer)와 glucosylsphingosine (GlcSph)의 농도가 증가하면서 신경세포의 심각한 손실이 야기되는 특징을 보인다. 신경교종에서 유래한 H4 세포를 GD에서 증가하는 기질인 GluCer와 GlcSph를 첨가하여 배양하였을 때, 심각한 DNA손상과 더불어 세포의 사멸이 야기되는 것과 이러한 신경세포의 사멸은 GluCer 보다는 GlcSph을 처리하였을 때 더 현저하게 증가하는 것을 관찰하였다. H4 세포에 히스톤 탈아세틸화 효소(HDAC) 6의 저해제인 tubacin과 GlcSph을 함께 처리하였을 경우에는 DNA손상은 물론 GlcSph에 의하여 유도된 세포사멸과 관련된 단백질 인자들의 발현이 모두 감소되었다. 본 연구를 통해 GlcSph이 세포사멸을 통하여 신경병증 GD의 발병에 주요한 역할을 한다는 것을 알 수 있었고, HDAC6 저해제가 신경병증 GD 환자를 위한 치료제 후보물질로 제시될 수 있는 가능성을 확인하였다.

• Natural Product Sciences
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• 제24권3호
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• pp.148-154
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• 2018

Chronic oxidative stress due to the accumulation of reactive oxygen species (ROS) in neuronal cells ultimately leads to neurodegenerative diseases. The use of natural therapies for the prevention of ROS-induced cell damage and for the treatment of neurodegenerative disorders has shown promising results. In this study, we evaluated the neuroprotective effects of the ethyl acetate (EtOAc) fraction of A. okamotoanum against the hydrogen peroxide ($H_2O_2$)-induced oxidative stress in C6 glial cells. Results show that cell viability was decreased in cells incubated with $H_2O_2$, whereas the addition of EtOAc fraction treatments in such cells significantly increased viability. The EtOAc fraction showed the highest inhibitory activity against ROS production and it also decreased the expressions of inflammatory proteins including cyclooxygenase-2, inducible nitric oxide synthase and interleukin-$1{\beta}$. Furthermore, the EtOAc fraction inhibited apoptosis by regulating the protein expressions cleaved caspase -9, -3, poly ADP ribose polymerase, Bax and Bcl-2. Therefore, these results show that the EtOAc fraction of A. Okamotoanum exhibits neuroprotective effects against $H_2O_2$ induced oxidative damage by regulating the inflammatory reaction and apoptotic pathway.

• 한국발생생물학회:학술대회논문집
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• 한국발생생물학회 2003년도 제3회 국제심포지움 및 학술대회
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• pp.71-71
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• 2003

Human umbilical cord blood cells(HUCBC) are rich in mesenchymal progenitor cells, endothelial cell precursors and hematopoietic cells. HUCBC have been used as a source of transplantable stem and progenitor cells. However, little is known about survival and development of HUCBC transplantation in the CNS. Estrogen has a neuroprotective potential against oxidative stress-induced cell death so has an effect on reducing infarct size of ischemic brain. We investigated the potential use of HUCBC as donor cells and tested whether estrogen mediates intravenously infused HUCBC enter and survive in ischemic brain. PKH26 labeled mononuclear fraction of HUCBC were injected into the tail vein of ischemic OVX rat brain with or without $17\beta$-estradiol valerate(EV). Under fluorescence microscopy, labeled cells were observed in the brain section. Significantly more cells were found in the ischemic brain than in the non-ischemic brain. HUCBC transplanted into ischemic brain could migrate and survive. Some of cells have shown neuronal like cells in hippocampus, striatum and cortex tissues. These result suggest that estrogen reduces ischemic damage and increases the migration of human umbilical cord blood cells. This Study was supported by the Korea Science and Engineering Foundation(KOSEF) though the Biohealth Products Research Center(BPRC), Inje University, Korea.

• 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.

• Journal of Microbiology and Biotechnology
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• 제31권6호
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• pp.867-874
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• 2021

Epalrestat (EPS) is a brain penetrant aldose reductase inhibitor, an approved drug currently used for the treatment of diabetic neuropathy. At near-plasma concentration, EPS induces glutathione biosynthesis, which in turn reduces oxidative stress in the neuronal cells. In this study, we found that EPS reduces neurodegeneration by inhibiting reactive oxygen species (ROS)-induced oxidative injury, mitochondrial membrane damage, apoptosis and tauopathy. EPS treatment up to 50 µM did not show any toxic effect on SH-SY5Y cell line (neuroblastoma cells). However, we observed toxic effect at a concentration of 100 µM and above. At 50 µM concentration, EPS showed better antioxidant activity against H₂O₂ (100 µM)-induced cytotoxicity, ROS formation and mitochondrial membrane damage in retinoic acid-differentiated SH-SY5Y cell line. Furthermore, our study revealed that 50 µM of EPS concentration reduced the glycogen synthase kinase-3 β (GSK3-β) expression and total tau protein level in H₂O₂ (100 µM)-treated cells. Findings from this study confirms the therapeutic efficacy of EPS on regulating Alzheimer's disease (AD) by regulating GSK3-β and total tau proteins phosphorylation, which helped to restore the cellular viability. This process could also reduce toxic fibrillary tangle formation and disease progression of AD. Therefore, it is our view that an optimal concentration of EPS therapy could decrease AD pathology by reducing tau phosphorylation through regulating the expression level of GSK3-β.

• 대한한의학회지
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• 제28권3호통권71호
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• pp.216-231
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• 2007

Objectives : Chengsimyeunja-eum and Sunghyangjungi-san are prescriptions used for cerebral infarction clinically; it is known that these formulas reduce ischemic damage. According to previous research data, controlling certain types of glucose is considered to decrease the risk of cerebral infarction. Based on this fact, we investigated the effects of Chengsimyeunja-eum and Sunghyangjungi-san extracts on reperfusion following ischemic damage to diabetic rats, the change of c-FOS and Bax positive neurons in the hippocampus and cerebral cortex and protein through immunohistochemical methods, changes of serum glucose level, serum triglyceride level, and hepatic glucokinase activity. Methods : We induced ischemic damaged in diabetic rats, and the rats were administered Chengsimyeunja-eum and Sunghyangjungi-san extracts. Results : Chengsimyeunja-eum demonstrated significant decrease of c-Fos positive neurons in both hippocampus and cerebral cortex as well as a significant decrease of Bax positive neurons in hippocampus after ischemic damage on diabetic rats and decrease of serum glucose level after ischemic damage on diabetic rats. Sunghyangjungi-san demonstrated significant decreases of c-Fos and Bax positive neurons in both hippocampus and cerebral cortex after ischemic damage on diabetic rats. Conclusions : Chengsimyeunja-eum, effect on glucose level control, has a remarkable effect of protection of neurons not effective on glucose level. Sunghyangjungi-san showed neuroprotective effect through preventing neuronal cell death.

• Archives of Pharmacal Research
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• 제27권4호
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• pp.454-459
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• 2004

The present study investigated the effects of gossypin, 3,3',4',5,7,8-hexahydroxyflavone 8-glucoside, on the toxicity induced by oxidative stress or $\beta$-amyloid ($A_{\beta}$) in primary cultured rat cortical cells. The antioxidant properties of gossypin were also evaluated by cell-free assays. Gossypin was found to inhibit the oxidative neuronal damage induced by xanthinelxanthine oxidase or by a glutathione depleting agent, D,L-buthionine (S,R)-sulfoximine. In addition, gossypin significantly attenuated the neurotoxicity induced by $A_{{\beta}(25-35)}$. Furthermore, gossypin dramatically inhibited lipid peroxidation initiated by $Fe^{2+}$ and ascorbic acid in rat brain homogenates. It also exhibited potent radical scavenging activity generated from 1 ,1-diphenyl-2-picrylhydrazyl. These results indicate that gossypin exerts neuroprotective effects in the cultured cortical cells by inhibiting oxidative stress- and $A_{\beta}$-induced toxicity, and that the antioxidant properties of gossypin may contribute to its neuroprotective actions.

• 생약학회지
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• 제44권4호
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• pp.379-383
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• 2013

Portulaca oleracea L. is known to have many biological benefits such as anti-oxidant, anti-inflammatory, anti-allergic and anti-tumor. The objective of this study is to explore the neuroprotective effect of P. oleracea L. against glutamate-induced oxidative stress in mouse hippocampal HT22 cells. P. oleracea L. 70% ethanol extract and solvent fractions have the potent neroprotective effects on glutamate-induced nerotoxicity by induced the expression of heme oxygenase (HO)-1 in HT22 cells. Especially, ethyl acetate fraction showed higher protective effect. In HT22 cell, P. oleracea L. treatment with ERK inhibitor (PD98059) and c-JUN N-terminal kinase (JNK) inhibitor (SP600125) reduced P. oleracea L. ethyl acetate fraction induced HO-1 expression and P. oleracea L. ethyl acetate fraction also increased ERK and JNK phosphorylation. Furthermore, we found that treatment of P. oleracea L. caused the nuclear accumulation of Nrf2. In conclusion, the ethyl acetate fraction of 70% ethanol extract of P. oleracea L. significantly protect glutamate-induced oxidative damage by induction of HO-1 via Nrf2, ERK and JNK pathway in mouse hippocampal HT22. Taken together these finding suggest that P. oleracea L. ethyl acetate fraction is good source for taking active compounds and may be a potential therapeutic agent for brain disorder that induced by oxidative stress and neuronal damage.

• 약학회지
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• 제43권4호
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• pp.535-540
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• 1999

Glutamate (Glu) receptor-mediated excitoxicity has been implicated in many acute and chronic types of neurological disorders. Exposure of mature rat cortical neurons (15-18 days in culture) to the various concentrations of Glu resulted in a marked neuronal death, whereas immature rat cortical neurons (4∼5 days in culture) were resistant to the Glu-induced toxicity. Glu receptor subtype-specific agonists showed differential extent of toxicity in the immature neurons. The neurons treated with NMDA or kainate (KA) did not exhibit damage. However, quisqualate (QA) treatment induced a considerable cell death (36.1%) in immature enurons. The non-NMDA antagonist DNQX did not reduce this response. Interestingly, the QA-induced toxicity was potentiated by spermine in a concentration-dependent manner. Again, the spermine-enhanced damage was not altered by the polyamine antagonist ifenprodil. Taken together, unlike NMDA or KA, QA can induce neurotoxicity in immature rat cortical neurons and the QA-induced toxicity was potentiated by spermine. The lack of antagonizing effects of DNQX and ifenprodil on QA-induced toxicity and the potentiated toxicity by spermine, respectively, implies that both QA receptor and the polyamine site of NMDA receptor may not mediate the neurotoxicity observed in this study, and that a distinct mechanism(s) may be involved in excitotoxicity in immature neurons.

• 대한한의학회지
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• 제22권1호
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• pp.63-77
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• 2001

Objectives : In acute stage of CVA, many patients experience Bugibultong as a symptom. Daesiho-tang is one of the most useful prescriptions for constipated stroke patients. This study investigated the effects of Daesiho-tang extracts on hypoxic E18 cortical neuroblast. Methods : To evaluate the effect of Daesiho-tang extracts on enuronal death caused by hypocia the neuronal viability and protein expressions of NMDA receptor subunits, ${\alpha}CaMK$ II PDE2 PSD95 densin-180, $eEF-l{\alpha}$ and GFAP were investigated. Results : We guessed that Daesiho-tang extracts worked to protect against cell damage through effecting on the protein expression of PSD(post synatpic density), especially increase of ${\alpha}CaMK$ II, $eEF-l{\alpha}$ PDE2, PSD95 and densin-180 Conclusions : According to the above results, it is supposed that Daesiho-tang is clinically applicable to stroke patients in the acute stage.