• Natural Product Sciences
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• 제18권1호
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• pp.26-31
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• 2012

Actinidia arguta (Actinidiaceae) has been reported to have several pharmacological effects such as anti-inflammatory, anti-allergic, and anti-oxidant activities. The present study investigated the protective activity of an ethanol extract from the leaf and stem of A. arguta against glutamate-induced neurotoxicity using cultured rat cortical neurons. Exposure of cultured cortical neurons to $500{\mu}M$ glutamate for 12 h triggered neuronal cell death. A. arguta inhibited glutamate-induced neuronal death and apoptosis, which were measured by a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) assay and Hoechst 33342 staining, respectively. The increase of pro-apoptotic proteins, Bax and c-caspase-3, in glutamate-treated neurons was significantly inhibited by treatment with A. arguta. A. arguta also inhibited $500{\mu}M$ glutamate-induced elevation of intracellular calcium concentration ($[Ca^{2+}]_i$) and reactive oxygen species (ROS) generation, which were measured by fluorescent dyes, Fluo-4 AM and $H_2DCF$-DA, respectively. These results suggest that A. arguta may prevent glutamate-induced apoptotic neuronal death by inhibiting $[Ca^{2+}]_i$ elevation and ROS generation and, therefore, may have a therapeutic role for the prevention of neurodegeneration in cerebral ischemic diseases.

• Biomolecules & Therapeutics
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• 제30권6호
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• pp.570-575
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• 2022

Stress breaks body balance, which can cause diverse physiological disorders and worsen preexisting diseases. However, recent studies have reported that controllable stress and overcoming from stress reinforce resilience to resist against more intense stress afterwards. In this study, we investigated the protective effect of corticosterone (CORT), a representative stress hormone against hydrogen peroxide (H₂O₂)-induced neuronal cell death and its underlying molecular mechanism in SH-SY5Y cells, a human neuroblastoma cell line. The decreased cell viability by H₂O₂ was effectively restored by the pretreatment with low concentration of CORT (0.03 μM for 72 h) in the cells. H₂O₂-increased expression of apoptotic markers such as PUMA and Bim was decreased by CORT pretreatment. Furthermore, pretreatment of CORT attenuated H₂O₂-mediated oxidative damages by upregulation of antioxidant enzymes via activation of nuclear factor erythroid 2-related factor 2 (Nrf2). These findings suggest that low concentration of CORT with eustressed condition enhances intracellular self-defense against H₂O₂-mediated oxidative cell death, suggesting a role of low concentration of CORT as one of key molecules for resilience and neuronal cell survival.

• 대한한의학회지
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• 제26권4호
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• pp.98-107
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• 2005

Objectives: Acupuncture treatment has been clinically used for functional recovery in Parkinson's disease. In the present study, we investigated the effect of acupuncture at Zusanli (ST36) on nigrostriatal dopaminergic neuronal cell death in rats. Methods: A Parkinson's disease model was induced by the unilateral injection of 6-hydroxydopamine (6-OHDA) into the striatum. Acupuncture treatment was performed at Zusanli (ST36) and at the hip, as a non-acupoint, once a day for 14 days. Two weeks after 6-0HDA injection, an apomorphine-induced rotational behavior test showed significant rotational asymmetry in rats with Parkinson's disease. Immunostaining for tyrosine hydroxylase demonstrated a dopaminergic neuronal loss in the substantia nigra and dopaminergic fiber loss in the striatum. Results: Acupuncture at the ST36 acupoint significantly inhibited rotational asymmetry in rats with Parkinson's disease, and also protected against 6-OHDA-induced nigrostriatal dopaminergic neuronal loss. These effects of acupuncture were not observed for non-acupoint acupuncture. Conclusions: The present study shows that acupuncture treatment, especially at the ST36 acupoint, can be used as a useful strategy for the treatment of Parkinson's disease.

• 한국독성학회:학술대회논문집
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• 한국독성학회 2003년도 추계학술대회
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• pp.145-145
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• 2003

Familial form of Alzheimer's disease (FAD) is caused by mutations in presenilin-1 (PS-1) and presenilin-2 (PS-2). PS1 and PS2 mutation are known to similar effects on the production of amyloid ${\beta}$ peptide (A${\beta}$) and cause of neuronal cell death in the brain of patient of AD. The importance of the alternation of cellular calcium homeostasis in the neuronal cell death by PS1 mutation in a variety of experimental systems has been demonstrated.(omitted)

• Molecular & Cellular Toxicology
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• 제4권1호
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• pp.16-21
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• 2008

Cell death of trophoblast, particularly by abnormal release of physiological nitric oxide (NO) has been known to be a causative factor of pre-eclampsia. In the present study, effects of intracellular calcium increase enhancing the activity of NO synthases (neuronal NO synthase, nNOS in this trophoblast cells) on the cell death were examined in a human placental full-term cell line (HT-1). Furthermore, we analyzed the possible mechanisms underlying the augmentation of $Ca^{++}$-mediated NOS activity mediated by protein kinases like PKC, PKA, or CaM-KII. In experiments for cell toxicity, a calcium ionophore (ionomycin $10{\mu}M$) enhanced cell death confirmed by MTT assay, and increased significantly nNOS activity determined with a hemoglobin oxidation assay. This cell death was partially protected by pre-treatment of 7-nitroindazole (7-NI, $10{\mu}M$ and $100{\mu}M$), a nNOS-specific inhibitor. Additionally, $Ca^{++}$-ionophore -induced increase of nNOS activity also was partially normalized by pre-treatment of specific inhibitors of protein kinases, PKC, PKA or CaM-KII. Therefore, we suggest that an increase of calcium influx, leading to the activation of nNOS activity, which in turn may result in the death of trophoblast cells by involvement of signaling mechanisms of protein kinases.

• 한국식품저장유통학회지
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• 제14권4호
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• pp.425-430
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• 2007

Amyloid ${\beta}-peptide$에 의해 유도되는 세포사멸을 보호하는 물질을 검색하기 위하여 250여 식물 재료 및 식품성분으로부터 스크리닝한 결과 가장 효과가 있는 시금치 추출물을 이용하여 뇌신경세포사멸(neuronal cell death)을 어느 정도 보호할 수 있는지를 알아보았다. 시금치 추출물이 항산화 활성과 acetylcholinesterase 활성에 대한 저해효과는 시금치 추출물 처리농도가 높을수록 유의적으로 높게 나타났다. 과산화수소와 amyloid ${\beta}-peptide$에 의해 유도된 SH-SY5Y 세포주의 세포사멸에 대한 시금치추출액의 억제효과를 살펴본 결과, 과산화수소에 의한 세포사멸에 대하여 시금치 추출물은 억제효과를 나타내었으나, amyloid ${\beta}-peptide$의 경우는 세포사멸억제효과를 나타내지 않았다.

• BMB Reports
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• 제29권3호
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• pp.200-204
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• 1996

Nerve growth factor (NGF) is literally known to promote neural differentiation and survival in several peripheral and central neurons. Thus, it is Widely believed that NGF may serve as a therapeutic agent for many types of neuronal diseases. One of the mechanisms suggested to explain the protective role of NGF is that the trophic factor can prevent the increase of intracellular calcium ions which might be responsible for neural death. To examine whether or not the calcium hypothesis works even under pathological conditions, we applied NGF to cultures deprived of glucose. Surprisingly, what was observed here is that NGF rather promoted cell death under a glucose-deprived condition. What we call the NGF paradox phenomenon occurred in a calcium concentration-dependent manner, indirectly suggesting that NGF might increase intracellular calcium ions in cells deprived of glucose. This suggestion is further supported by the fact that nifedipine, a well-known L-type calcium channel blocker, could block the cell death potentiated by NGF. Here it is still premature to propose the complete mechanism underlying the NGF paradox phenomenon. However, this study certainly indicates that NGF as a therapeutic agent for neuronal diseases should be carefully considered before use.

• The Korean Journal of Physiology and Pharmacology
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• 제17권1호
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• pp.15-21
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• 2013

Aspirin (acetylsalicylic acid) is one of the most widely used therapeutic agents based on its pharmacological actions, including anti-inflammatory, analgesic, anti-pyretic, and anti-thrombotic effects. In this study, we investigated the effects of aspirin on seizure susceptibility and hippocampal neuropathology following pilocarpine-induced status epilepticus (SE). SE was induced by pilocarpine hydrochloride (280 mg/kg, i.p.) administration in C57BL/6 mice (aged 8 weeks). Aspirin was administered daily (15 mg/kg or 150 mg/kg, i.p.) for 10 days starting 3 days before SE, continuing until 6 days after SE. After pilocarpine injection, SE onset time and mortality were recorded. Neuronal cell death was examined using cresyl violet and Fluoro-Jade staining, and glial responses were observed 7 days post SE using immunohistochemistry. In the aspirin-treated group, the onset time of SE was significantly shortened and mortality was markedly increased compared to the control group. However, in this study, aspirin treatment did not affect SE-induced neuronal cell death or astroglial and microglial responses in the hippocampus. In conclusion, these results suggest that the safety of aspirin should be reevaluated in some patients, especially with neurological disorders such as temporal lobe epilepsy.

• The Korean Journal of Physiology and Pharmacology
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• 제26권3호
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• pp.227-227
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• 2022

• Journal of Nutrition and Health
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• 제48권5호
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• pp.451-456
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• 2015

Purpose: Neuronal apoptotic events induced by aging and hypoxic/ischemic conditions is an important risk factor in neurodegenerative diseases such as ischemia stroke and Alzheimer's disease. The peel of Citrus sunki Hort. ex Tanaka has long been used as a traditional medicine, based on multiple biological activities including anti-oxidant, anti-inflammation, and anti-obesity. In the current study, we examined the actions of fermented C. sunki peel extract against cobalt chloride ($CoCl_2$)-mediated hypoxic death in human neuroblastoma SH-SY5Y cells. Methods: Cell viability was measured by trypan blue exclusion. Expression of apoptosis related proteins and release of cytochrome c were detected by western blot. Production of intracellular reactive oxygen species (ROS) and apoptotic morphology were examined using 2',7'-dichlorofluorescin diacetate (DCF-DA) and 4',6-diamidino-2-phenylindole (DAPI) staining. Results: Exposure to $CoCl_2$, a well-known mimetic agent of hypoxic/ischemic condition, resulted in neuronal cell death via caspase-3 dependent pathway. Extract of fermented C. sunki peel significantly rescued the $CoCl_2$-induced neuronal toxicity with the cell viability and appearance of apoptotic morphology. Cytoprotection with fermented C. sunki peel extract was associated with a decrease in activities of caspase-3 and cleavage of poly (ADP ribose) polymerase (PARP). In addition, increase in the intracellular ROS and release of cytochrome c from mitochondria to the cytosol were inhibited by treatment with extract of fermented C. sunki peel. Conclusion: Based on these data, fermented C. sunki peel extract might have a protective effect against $CoCl_2$-induced neuronal injury partly through generation of ROS and effectors involved in mitochondrial mediated apoptosis.