• Title/Summary/Keyword: Neuroprotective agents

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Neuronal Cytotoxicity of Oxygen Radical in Newborn Mouse Forebrain Culture

  • Lim, Kye-Taek;Park, Seung-Taeck;Choi, Min-Kyu;Chung, Yeun-Tai
    • Toxicological Research
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    • v.11 no.2
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    • pp.187-192
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    • 1995
  • The cytotoxic effects of hydrogen peroxide and neuroprotective effects of a variety of agents were investigated in newborn mouse forebrain tissue culture. In our experiments, oxygen radical was generated enzymatically by glucose oxidase and the values were expressed as a percentage of number of living cells by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Cytotoxicity of oxygen radicals was prevented by catalase and (N, N, N', N', -tetrakis (2-pyridylmethyl) ethylenediamine (TPEN), but N-tetra-ot-butyl-phenylnitrone (PBN), and deferoxamine (DFX), failed to show protective effects against oxygen radicals. Antagonists of the N-methyl-D-aspartate (NMDA) receptor, D-2-amino-5-phosphonovaleric acid (APV), 7-chlorokynurenic acid (CKA), and MK801 (a non-competitive NMDA antagonist) were also not effective in blocking neurotoxicity induced by glucose oxidase generated oxygen radicals.

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Current Concept and Future of the Management of Spinal Cord Injury: A Systematic Review (척수손상 치료 약제의 현재와 미래: 체계적 고찰)

  • Choi, Il;Ha, Jin Gyeong;Jeon, Sang Ryong
    • Journal of Trauma and Injury
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    • v.26 no.3
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    • pp.63-73
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    • 2013
  • Spinal cord injury (SCI) is a serious condition associated with social and familial burden, as well as significant neurologic deficit. Despite the many advances in the treatment of spinal cord injury, a fundamental treatment for neurologic functional recovery has not yet been developed. In this article, we review two directions of development for spinal cord injury treatment: neuroprotective pharmacological agents and axon-regenerating cell therapy. We expect developments in these two to lead to improve functional recovery in patients with spinal cord injuries and to reduce burdens on society, as well as the patients' families.

Neuroprotective Effects of Carpinus tschonoskii MAX on 6-Hydroxydopamine-Induced Death of PC12 Cells

  • Kim, Min-Kyoung;Kim, Sang-Cheol;Kang, Jung-Il;Boo, Hye-Jin;Hyun, Jin-Won;Koh, Young-Sang;Park, Deok-Bae;Yoo, Eun-Sook;Kang, Ji-Hoon;Kang, Hee-Kyoung
    • Biomolecules & Therapeutics
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    • v.18 no.4
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    • pp.454-462
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    • 2010
  • The present study investigated the neuroprotective effect of Carpinus tschonoskii MAX and its intracellular protective mechanism on 6-hydroxydopamine (6-OHDA)-induced oxidative damage in PC12 cells. We found that pretreatment of PC12 cells with C. tschonoskii extract significantly inhibited the cell death induced by 6-OHDA in a dose dependent manner. C. tschonoskii extract decreased 6-OHDA-induced apoptotic events such as chromatin condensation, DNA fragmentation, the decrease of Bcl-2/Bax ratio, caspase-3 activation and PARP cleavage. C. tschonoskii extract also reduced generation of 6-OHDA-induced reactive oxygen species and nitric oxide. Furthermore, C. tschonoskii extract up-regulated the myocyte enhancer factor 2 D (MEF2D), a critical transcription factor for neuronal survival, and Akt activity, whereas it inhibited the activity of ERK1/2 and JNK. The results suggest that C. tschonoskii extract decreases 6-OHDA-induced oxidative stress and could prevent PC12 cell apoptosis induced by 6-OHDA via the up-regulation of MEF2D and Akt activity, and thus may have application in developing therapeutic agents for Parkinson's disease.

Neuroprotective Effects of Korean Red Pine (Pinus densiflora) Bark Extract and Its Phenolics

  • Kim, Ji-Won;Im, Sungbin;Jeong, Ha-Ram;Jung, Young Sung;Lee, Inil;Kim, Kwan Joong;Park, Seung Kook;Kim, Dae-Ok
    • Journal of Microbiology and Biotechnology
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    • v.28 no.5
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    • pp.679-687
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    • 2018
  • Korean red pine (Pinus densiflora) is one of the major Pinus species in Korea. Red pine bark is removed prior to the chipping process in the wood industry and discarded as waste. However, red pine bark contains a considerable amount of naturally occurring phenolics, including flavonoids, and therefore may have a variety of biological effects. In this study, we investigated if Korean red pine bark extract (KRPBE) could protect neuronal PC-12 cells from oxidative stress and inhibit cholinesterase activity. Analysis of reversed-phase high-performance liquid chromatography results revealed four phenolics in KRPBE: vanillin, protocatechuic acid, catechin, and taxifolin. The total phenolic and flavonoid contents of KRPBE were 397.9 mg gallic acid equivalents/g dry weight (DW) and 248.7 mg catechin equivalents/g DW, respectively. The antioxidant capacities of KRPBE measured using ABTS, DPPH, and ORAC assays were 697.3, 521.8, and 2,627.7 mg vitamin C equivalents/g DW, respectively. KRPBE and its identified phenolics protected against $H_2O_2$-induced oxidative cell death in a dose-dependent manner. Acetylcholinesterase and butyrylcholinesterase, which degrade the neurotransmitter acetylcholine to terminate neurotransmission in synaptic clefts, were inhibited by treatment with KRPBE and its identified phenolics. Taken together, these results suggest that KRPBE and its constituent antioxidative phenolics are potent neuroprotective agents that can maintain cell viability under oxidative stress and inhibit cholinesterase activity.

L-histidine and L-carnosine exert anti-brain aging effects in D-galactose-induced aged neuronal cells

  • Kim, Yerin;Kim, Yuri
    • Nutrition Research and Practice
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    • v.14 no.3
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    • pp.188-202
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    • 2020
  • BACKGROUND/OBJECTIVES: Brain aging is a major risk factor for severe neurodegenerative diseases. Conversely, L-histidine and L-carnosine are known to exhibit neuroprotective effects. The aim of this study was to examine the potential for L-histidine, L-carnosine, and their combination to mediate anti-brain aging effects in neuronal cells subjected to D-galactose-induced aging. MATERIALS/METHODS: The neuroprotective potential of L-histidine, L-carnosine, and their combination was examined in a retinoic acid-induced neuronal differentiated SH-SY5Y cell line exposed to D-galactose (200 mM) for 48 h. Neuronal cell proliferation, differentiation, and expression of anti-oxidant enzymes and apoptosis markers were subsequently evaluated. RESULTS: Treatment with L-histidine (1 mM), L-carnosine (10 mM), or both for 48 h efficiently improved the proliferation, neurogenesis, and senescence of D-galactose-treated SH-SY5Y cells. In addition, protein expression levels of both neuronal markers (β tubulin-III and neurofilament heavy protein) and anti-oxidant enzymes, glutathione peroxidase-1 and superoxide dismutase-1 were up-regulated. Conversely, protein expression levels of amyloid β (1-42) and cleaved caspase-3 were down-regulated. Levels of mRNA for the pro-inflammatory cytokines, interleukin (IL)-8, IL-1β, and tumor necrosis factor-α were also down-regulated. CONCLUSIONS: To the best of our knowledge, we provide the first evidence that L-histidine, L-carnosine, and their combination mediate anti-aging effects in a neuronal cell line subjected to D-galactose-induced aging. These results suggest the potential benefits of L-histidine and L-carnosine as anti-brain aging agents and they support further research of these amino acid molecules.

Biruloquinone, an Acetylcholinesterase Inhibitor Produced by Lichen-Forming Fungus Cladonia macilenta

  • Luo, Heng;Li, Changtian;Kim, Jin Cheol;Liu, Yanpeng;Jung, Jae Sung;Koh, Young Jin;Hur, Jae-Seoun
    • Journal of Microbiology and Biotechnology
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    • v.23 no.2
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    • pp.161-166
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    • 2013
  • At present, acetylcholinesterase (AChE) inhibitors are the first group of drugs to treat mild to moderate Alzheimer's disease (AD). Although beneficial in improving cognitive and behavioral symptoms, the effectiveness of AChE inhibitors has been questioned since they do not delay or prevent neurodegeneration in AD patients. Therefore, in the present study, in order to develop new and effective anti-AD agents from lichen products, both the AChE inhibitory and the neuroprotective effects were evaluated. The AChE inhibitory assay was performed based on Ellman's reaction, and the neuroprotective effect was evaluated by using the MTT method on injured PC12 cells. One AChE inhibitor ($IC_{50}$ = 27.1 ${\mu}g/ml$) was isolated by means of bioactivity-guided isolation from the extract of lichen-forming fungus Cladonia macilenta, which showed the most potent AChE inhibitory activity in previous screening experiment. It was then identified as biruloquinone by MS, and $^1H$- and $^{13}C$-NMR analyses. The inhibitory kinetic assay suggested that biruloquinone is a mixed-II inhibitor on AChE. Meanwhile, biruloquinone improved the viability of the $H_2O_2$- and ${\beta}$-amyloid-injured PC12 cells at 1 to 25 ${\mu}g/ml$. The protective effects are proposed to be related to the potent antioxidant activities of biruloquinone. These results imply that biruloquinone has the potential to be developed as a multifunctional anti- AD agent.

Autophagy inducing Effect of modified Yeoldahanso-tang and its related Proteins in SH-SY5Y cells (열다한소탕(熱多寒少湯) 가감방(加減方)의 자가탐식(自家貪食) 유도 활성과 관련 단백질 탐색)

  • Kim, Hee-Ju;Bae, Na-Young;Jang, Moon-Hee;Yang, Hyun-Ok;Ahn, Taek-Won
    • Journal of Sasang Constitutional Medicine
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    • v.25 no.3
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    • pp.208-217
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    • 2013
  • Objectives Modified Yeolda-Hanso tang (MYH) is a traditional herbal formula in Korea for various diseases. MYH is containing the 10 herbs : Pueraria lobata (Willd.) Ohwi, Angelica tenuissima Nakai, Scutellaria baicalensis Georgi, Platycodon grandiflorum (Jacq), Angelicae Dahurica, Cimicifuga heracleifolia Kom, Raphanus sativa L., Polygala tenuifolia (Willd), Acorus gramineus Soland and Dimocarpus longan Lour. The 10 herbs is constituted as a ratio of the 6:4:2:1:2:2:2:4:6:6. We investigated neuroprotective effects of MYH on human neuroblastoma SH-SY5Y cells and evaluated the ability of MYH to prevent and treat for neurodegenerative diseases such as Parkinson's disease via basal autophagy enhancement. Methods Pharmacological induction of Autophagy by MYH in SH-SY5Y cells: Induction of autophagy by MYH in human neuroblastoma SH-SY5Y cells was carreid out by immunoblot analysis with several autophagy markers. SH-SY5Y cells were treated with MYH at the concentration of 400 and $800{\mu}g/ml$ for 24 hr. Specifically, the autophagosome proteins LC3 II and Atg5 levels were increased and autophagy pathway related proteins such as beclin-1, PI3 Kinase class III protein, ULK1, mTOR and AMPK were activated. Conclusions MYH can enhance the induction of autophagy through key regulator AMPK, mTOR, and Beclin-1 and it should be considered as a possible candidate of neuroprotective agents for such as Parkinson's disease.

Neuroprotective Effects of Schisandra chinensis and Ribes fasciculatum Extract on Hydrogen Peroxide-Mediated Oxidative Stress in Neuroblastic SH-SY5Y Cell Line (과산화수소로 유도된 SH-SY5Y 신경세포 사멸에 대한 오미자·칠해목 추출혼합물의 보호효과)

  • Park, Eun-kuk;Han, Kyung-Hoon;Lee, Seung-Hee;Kim, Nam-Ki;Bae, Mun-Hyoung;Seo, Young-Ha;Yong, Yoon-joong;Jeong, Seon-Yong;Choi, Chun-Whan
    • The Korean Journal of Food And Nutrition
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    • v.31 no.6
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    • pp.865-872
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    • 2018
  • In neuronal cell deaths, oxidative stress is normally implicated with a most of these deaths occurring in neurodegenerative disorders such as the Alzheimer's and Parkinson's diseases. In this study, the neuroprotective effects of Schisandra chinensis (SC) and Ribes fasciculatum (RF) extracts on hydrogen peroxide ($H_2O_2$)-induced oxidative stress in neuroblastic cell line were investigated. For an hour, hydrogen peroxide of $100{\mu}M$ concentration, was induced on neuroblastic cells, causing apoptic cell death. For the neuroprotection, a sample of neuroblastic cells had been pre-treated with SC and RF extracts for 24 hours before application of the hydrogen peroxide. No neurotoxic effects were observed in the cells that had been treated by SC and RF. This prove that the treatment of SC and RF extract prevented apoptotic cell death of neuroblastic cell line exposed to oxidative injury. In addition, applying both SC and RF extracts at a 7:3 ratio increased the neuronal cell survival rate, compared to individual treatments of SC and RF extract. This study suggests that SC and RF extracts may be potential therapeutic agents for the prevention of neuronal cell death.

The Study about Characteristics Affecting Functional Recovery of Stroke Patients Treated in an Oriental Medical Center (한방병원에 입원한 뇌경색 환자의 기능회복과 관련된 특성에 대한 연구)

  • Kim, Young-Jee;Kim, Mi-Young;Lee, Seung-Yeop;Choi, Won-Woo;Park, Joo-Young;Kwon, Seung-Won;Jung, Woo-Sang;Moon, Sang-Kwan;Cho, Ki-Ho;Kim, Young-Suk;Park, Sung-Wook;Park, Jung-Mi;Ko, Chang-Nam;Bae, Hyung-Sup;Na, Byong-Jo
    • The Journal of Internal Korean Medicine
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    • v.30 no.4
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    • pp.719-731
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    • 2009
  • Objectives : Stroke is the most common disabling neurological disease of adult life. The treatment and rehabilitation of stroke patients is an important and challenging area in the field of medicine. In Korea, a lot of stroke patients are treated using oriental medicine and there have been reports on their functional recovery. The aim of this study was to prove the therapeutic effect of oriental medicine on ischemic stroke. We also tried to identify characteristics of patients whose functional recovery was prominent and studied whether or not the use of fluids, anticoagulants, antiplatelets and neuroprotective agents increased the functional recovery of patients. Methods : We studied 794 patients within 2 weeks after first attack of ischemic stroke who were admitted to Kyung-Hee Oriental Medical Center from 1999 to 2000. Their maximum admission period was 60 days. Results : Motor power grade, NIHSS and MBI scores of patients improved during hospitalization significantly. Factors affecting functional recovery were admission period, motor power grade, NIHSS and MBI at admission. Age, waist-hip ratio and HDL cholesterol also affected functional recovery of patients. Whether or not fluids, anticoagulants, antiplatelets and neuroprotective agents were administered had nothing to do with functional recovery. Conclusion : Oriental medicine is effective for treatment and rehabilitation of ischemic stroke patients. When we manage stroke, we have to consider some important factors.

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Protective Effect of Methanolic Extracts from Dendrobium nobile Lindl. on $H_{2}O_{2}$-induced Neurotoxicity in PC12 cells (석곡 MeOH 추출물이 $H_{2}O_{2}$에 의한 신경세포 보호효과에 미치는 영향)

  • Yoon, Mi-Young;Kim, Ju-Young;Hwang, Ji-Hwan;Cha, Mi-Ran;Lee, Mi-Ra;Jo, Kyung-Jin;Park, Hae-Ryong
    • Applied Biological Chemistry
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    • v.50 no.1
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    • pp.63-67
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    • 2007
  • The neuroprotective effect of methanolic extracts from Dendrobium nobile Lindl. (DME) against $H_{2}O_{2}$-induced neurotoxicity in PC12 cells was investigated. The treatment of PC12 cells with various DME concentrations under $H_{2}O_{2}$ resulted in the induction of protective effect in a dose-dependent manner, as determined by the results of an MTT reduction assay, an LDH release assays, and a morphological assay. Interestingly, we also detected reduction of apoptotic bodies and inhibition of caspase-3 activity by DME in $H_{2}O_{2}$-indeced PC12 cells. These data show that the neuroprotective effect of DME against PC12 cells might be related to the suppression of caspase-3 activation. Therefore, these results suggest that DME could be a new potential candidate as chemotherapeutic agents against neuronal diseases.