• 한국약용작물학회지
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• 제17권1호
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• pp.68-74
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• 2009

Vitis amurensis (VA; Vitaceae) has long been used in oriental herbal medicine. It has been reported that roots and seeds of VA have anti-inflammatory and antioxidant effects. In the present study, the protective effect of ethanol extract from stems and leaves of VA on hydrogen peroxide (${H_2}{O_2}$) (100 ${\mu}M$)-induced neuronal cell damage was examined in primary cultured rat cortical neurons. VA (10-100 ${\mu}g$/ml) concentration-dependently inhibited ${H_2}{O_2}$-induced apoptotic neuronal cell death measured by 3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) assay and Hoechst 33342 staining. VA inhibited ${H_2}{O_2}$-induced elevation of intracellular $Ca^{2+}$ concentration (${[Ca^{2+}]}_i$) and generation of reactive oxygen species (ROS), which were measured by fluorescent dyes. Pretreatment of VA also prevented glutamate release into medium induced by 100 ${\mu}M$ ${H_2}{O_2}$, which was measured by HPLC. These results suggest that VA showed a neuroprotective effect on ${H_2}{O_2}$-induced neuronal cell death by interfering with ${H_2}{O_2}$-induced elevation of ${[Ca^{2+}]}_i$, glutamate release, and ROS generation. This has a significant meaning of finding a new pharmacological activity of stems and leaves of VA in the CNS.

• BMB Reports
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• 제51권8호
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• pp.400-405
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• 2018

Chronic stress induces neuronal cell death, which can cause nervous system disorders including Parkinson's disease and Alzheimer's disease. In this study, we evaluated the neuroprotective effects of Clematis terniflora extract (CTE) against corticosterone-induced apoptosis in rat pheochromocytoma (PC12) cells, and also investigated the underlying molecular mechanisms. At concentrations of 300 and $500{\mu}g/ml$, CTE significantly decreased apoptotic cell death and mitochondrial damage induced by $200{\mu}M$ corticosterone. CTE decreased the expression levels of endoplasmic reticulum (ER) stress proteins GRP78, GADD153, and mitochondrial damage-related protein BAD, suggesting that it downregulates ER stress evoked by corticosterone. Furthermore, our results suggested that these protective effects were mediated by the upregulation of p-AKT and p-ERK1/2, which are involved in cell survival signaling. Collectively, our results indicate that CTE can lessen neural damage caused by chronic stress.

• Biomolecules & Therapeutics
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• 제29권3호
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• pp.321-330
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• 2021

Oxidative stress plays a crucial role in the development of neuronal disorders including brain ischemic injury. Thioredoxin 1 (Trx1), a 12 kDa oxidoreductase, has anti-oxidant and anti-apoptotic functions in various cells. It has been highly implicated in brain ischemic injury. However, the protective mechanism of Trx1 against hippocampal neuronal cell death is not identified yet. Using a cell permeable Tat-Trx1 protein, protective mechanism of Trx1 against hydrogen peroxide-induced cell death was examined using HT-22 cells and an ischemic animal model. Transduced Tat-Trx1 markedly inhibited intracellular ROS levels, DNA fragmentation, and cell death in H2O2-treatment HT-22 cells. Tat-Trx1 also significantly inhibited phosphorylation of ASK1 and MAPKs in signaling pathways of HT-22 cells. In addition, Tat-Trx1 regulated expression levels of Akt, NF-κB, and apoptosis related proteins. In an ischemia animal model, Tat-Trx1 markedly protected hippocampal neuronal cell death and reduced astrocytes and microglia activation. These findings indicate that transduced Tat-Trx1 might be a potential therapeutic agent for treating ischemic injury.

• 한국식품영양학회지
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• 제33권3호
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• pp.347-355
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• 2020

Cognitive impairment is considered to be key research topics in the field of neurodegenerative diseases and in understanding of learning and memory. In the present study, we investigated neuroprotective effects of Schisandra chinensis (SC) and Ribes fasciculatum (RF) extracts in hydrogen peroxide-induced neuronal cell death in vitro and scopolamine-induced cognitive impairment in Sprague Dawley^® (SD) rat in vivo. Apoptotic cell death in neuroblastic PC12 cell line was induced by hydrogen peroxide for 1 hour at 100 μM. However, mixture of SC and RF treatment prevented peroxide induced PC12 cell death with no neurotoxic effects. For in vivo experiment, the effect of SC and RF extracts on scopolamine-induced cognitive impairment in SD rat was evaluated by spontaneous alternation behavior in Y-Maze test. After 30 min scopolamine injection, the scopolamine-induced rats presented significantly decreased % spontaneous alteration and acetylcholine level, compared to non-induced group. However, treatment of SC+RF extracts rescued the reduced % spontaneous alteration with acetylcholine concentration from hippocampus in scopolamine-induced rats. These results suggested that mixture of SC and RF extract may be a potential natural therapeutic agent for the prevention of cognitive impairment.

• The Korean Journal of Physiology and Pharmacology
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• 제14권5호
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• pp.279-283
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• 2010

Urushinol, a plant allergen, has significantly restricted the medical application of $Rhus$ $verniciflua$, although it has been reported to possess a wide variety of biological activities such as anti-inflammatory, antioxidant, and anti-cancer actions. To reduce the urushinol content while maintaining the beneficial biological activities, mushroom-mediated fermentation of $Rhus$ $verniciflua$ was carried out and this method resulted in significantly attenuated allergenicity [1]. In the present study, to examine the neuroprotective properties of mushroom-fermented stem bark of $Rhus$ $verniciflua$, two constituents were isolated from mushroom-fermented bark and their neuroprotective properties were examined in a mouse model of kainic acid (KA)-induced excitotoxicity. KA resulted in significant apoptotic neuronal cell death in the CA3 region of mouse hippocampus. However, seven daily administrations of RVH-1 or RVH-2 prior to KA injection significantly attenuated KA-induced pyramidal neuronal cell death in the CA3 region. Furthermore, pretreatment with RVH-1 and RVH-2 also suppressed KA-induced microglial activation in the mouse hippocampus. The present study demonstrates that RVH-1 and RVH-2 isolated from $Rhus$ $verniciflua$ and detoxified using mushroom species possess neuroprotective properties against KA-induced excitotoxicity. This leads to the possibility that detoxified $Rhus$ $verniciflua$ can be a valuable asset in herbal medicine.

• 한국환경성돌연변이발암원학회:학술대회논문집
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• 한국환경성돌연변이발암원학회 2001년도 Korean Environmental Mutagen Society
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• pp.112-112
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• 2001

• BMB Reports
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• 제49권7호
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• pp.382-387
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• 2016

Reactive oxygen species generated under oxidative stress are involved in neuronal diseases, including ischemia. Glutathione S-transferase pi (GSTpi) is a member of the GST family and is known to play important roles in cell survival. We investigated the effect of GSTpi against oxidative stress-induced hippocampal HT-22 cell death, and its effects in an animal model of ischemic injury, using a cell-permeable PEP-1-GSTpi protein. PEP-1-GSTpi was transduced into HT-22 cells and significantly protected against H2O2-treated cell death by reducing the intracellular toxicity and regulating the signal pathways, including MAPK, Akt, Bax, and Bcl-2. PEP-1-GSTpi transduced into the hippocampus in animal brains, and markedly protected against neuronal cell death in an ischemic injury animal model. These results indicate that PEP-1-GSTpi acts as a regulator or an antioxidant to protect against oxidative stress-induced cell death. Our study suggests that PEP-1-GSTpi may have potential as a therapeutic agent for the treatment of ischemia and a variety of oxidative stress-related neuronal diseases.

• 생명과학회지
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• 제34권1호
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• pp.37-47
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• 2024

Fun14 도메인 함유 단백 1(Fun14 domain-containing protein 1, FUNDC1)은 미토콘드리아 외막에 존재하는 단백질로, 미토콘드리아의 마이토파지(mitophage) 기전 조절에 관여하는 것으로 알려져 있다. 본 연구에서는 해마 뉴런 기원의 HT-22 세포에서 아밀로이드 베타 펩티드(A_β)에 의한 미토콘드리아와 세포 손상 과정에서 FUNDC1의 개재 가능성과 역할을 조사하였다. HT-22 세포에서 A_β를 처리하면 처리 시간에 의존적으로 FUNDC1의 발현 감소가 관찰되었다. 또한 MTT 환원능과 세포 내 ATP 농도, 미토콘드리아 막전압의 감소, 반응성 산소종의 생성과 미토콘드리아 Ca²⁺ 부하의 증가 등 미토콘드리아의 기능적 손상을 나타내는 지표들의 변화와 함께 세포사멸의 증가가 관찰되었다. FUNDC1의 발현을 일시적으로 차단한 세포군에서도 미토콘드리아의 기능적 손상을 나타내는 지표 변화와 세포사멸의 증가가 관찰되었다. 반면에 FUNDC1을 일시적으로 과발현시킨 세포군에서는 A_β 처리에 의한 미토콘드리아 손상과 세포 사멸이 유의하게 억제되었다. 이와 같은 결과들은 A_β에 의한 미토콘드리아와 세포 손상 기전에 FUNDC1이 중요하게 관여할 가능성을 시사한다.

• 생물정신의학
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• 제5권2호
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• pp.219-226
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• 1998

Cytosine arabinoside(AraC) inhibits DNA synthesis and ${\beta}$-DNA polymerase, an enzyme involved in DNA repair. This, a potent antimitotic agent, is clinically used as an anticancer drug with side effect of severe neurotoxicity. Earlier reports suggested that inhibition of neuronal survival by AraC in sympathetic neuron may be due to the inhibition of a 2'-deoxycytidine-dependent process that is independent of DNA synthesis or repair and AraC induced a signal that is triggers a cascade of new mRNA and protein synthesis, leading to apoptotic cell death in cultured cerebellar granule cells. The present study would suggest whether caspase family(ICE/CED-3-like protease) involved in AraC-induced apoptosis pathway of PC12 cells. It was observed that treatment of PC12 cells with AraC led to decrease of viability by MTT assay and morphology changes, which did not suggest that AraC induced apoptosis in PC12 cells. The mRNA of caspase-1/caspase-3 were expressed in PC12 cells constitutively, and AraC did not activate caspase family. These results suggest that caspase-1/caspase-3 may not be required for AraC-induced cell death pathway in PC12 cells.

• 한방재활의학과학회지
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• 제23권1호
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• pp.1-13
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• 2013

Objectives : The pathophysiology of acute spinal cord injury(SCI) may be divided into primary and secondary mechanisms of injury. The secondary mechanism involves free radical formation, excitotoxicity, inflammation and apoptotic cell death, and sets in minutes after injury and lasts for weeks or months. During this phase the spinal tissue damages are aggravated. Therefore, secondary mechanisms of injury serve as a target for the development of neuroprotective drug against SCI. The present study investigated the effect of tetramethylpyrazine(TMP), an active ingredient purified from the rhizome of Ligusticum wallichii(川芎, chuanxiong), on neuronal apoptosis in spinal cord compression injury in rats. Methods : SCI was subjected to rats by a static compression method(35 g weight, 5 mins) and TMP was treated 3 times(30 mg/kg, i.p.) during 48 hours after the SCI. Results : TMP ameliorated the tissue damage in peri-lesion of SCI and reduced TUNEL-labeled cells both in gray matter and in white matter significantly. TMP also attenuated Bax-expressed motor neurons in the ventral horn and preserved Bcl-2-expressed motor neurons. Conclusions : These results indicate that TMP plays a protective role in apoptotic cell death of neurons and oligodendrocytes in spinal cord injury. Moreover, it is suggested that TMP and TMP-containing chuanxiong may potentially delay or protect the secondary spinal injury.