• 제목/요약/키워드: Neuroprotective agents

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Neuroprotective Effects of Kaempferol, Quercetin, and Its Glycosides by Regulation of Apoptosis (Kaempferol, quercetin 및 그 배당체들의 apoptosis 조절을 통한 신경세포 보호 효과)

  • Kim, Ji Hyun;Lee, Sanghyun;Cho, Eun Ju;Kim, Hyun Young
    • Journal of the Korea Academia-Industrial cooperation Society
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    • 제20권2호
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    • pp.286-293
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    • 2019
  • Alzheimer's disease (AD) is a neurodegenerative disease caused by accumulation of amyloid beta ($A{\beta}$) in the brain. In the present study, we investigated the neuroprotective effects of four flavonoids such as kaempferol, kaempferol-3-O-glucoside, quercetin, and quercetin-3-${\beta}$-D-glucoside against neuronal apoptosis induced by $A{\beta}$ in SH-SY5Y neuronal cells. Treatment with $A{\beta}$ decreased cell viability compared to the non-treated normal group. However, treatment with the four flavonoids increased cell viability in SH-SY5Y cells treated with $A{\beta}$. In addition, we measured the expression of apoptosis-related proteins such as Bcl-2-associated X protein (Bax) and cleaved caspase-9. Treatment with the four flavonoids down-regulated Bax and cleaved caspase-9 in $A{\beta}$-treated SH-SY5Y neuronal cells. Overall, the results of the present study demonstrated the neuroprotective effect of flavonoids by anti-apoptotic activity in $A{\beta}$-induced SH-SY5Y neuronal cells. These results suggest that these four flavonoids would be useful therapeutic and prevention agents for AD.

Notoginseng leaf triterpenes ameliorates mitochondrial oxidative injury via the NAMPT-SIRT1/2/3 signaling pathways in cerebral ischemic model rats

  • Weijie, Xie;Ting, Zhu;Ping, Zhou;Huibo, Xu;Xiangbao, Meng;Tao, Ding;Fengwei, Nan;Guibo, Sun;Xiaobo, Sun
    • Journal of Ginseng Research
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    • 제47권2호
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    • pp.199-209
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    • 2023
  • Background: Due to the interrupted blood supply in cerebral ischemic stroke (CIS), ischemic and hypoxia results in neuronal depolarization, insufficient NAD+, excessive levels of ROS, mitochondrial damages, and energy metabolism disorders, which triggers the ischemic cascades. Currently, improvement of mitochondrial functions and energy metabolism is as a vital therapeutic target and clinical strategy. Hence, it is greatly crucial to look for neuroprotective natural agents with mitochondria protection actions and explore the mediated targets for treating CIS. In the previous study, notoginseng leaf triterpenes (PNGL) from Panax notoginseng stems and leaves was demonstrated to have neuroprotective effects against cerebral ischemia/reperfusion injury. However, the potential mechanisms have been not completely elaborate. Methods: The model of middle cerebral artery occlusion and reperfusion (MCAO/R) was adopted to verify the neuroprotective effects and potential pharmacology mechanisms of PNGL in vivo. Antioxidant markers were evaluated by kit detection. Mitochondrial function was evaluated by ATP content measurement, ATPase, NAD and NADH kits. And the transmission electron microscopy (TEM) and pathological staining (H&E and Nissl) were used to detect cerebral morphological changes and mitochondrial structural damages. Western blotting, ELISA and immunofluorescence assay were utilized to explore the mitochondrial protection effects and its related mechanisms in vivo. Results: In vivo, treatment with PNGL markedly reduced excessive oxidative stress, inhibited mitochondrial injury, alleviated energy metabolism dysfunction, decreased neuronal loss and apoptosis, and thus notedly raised neuronal survival under ischemia and hypoxia. Meanwhile, PNGL significantly increased the expression of nicotinamide phosphoribosyltransferase (NAMPT) in the ischemic regions, and regulated its related downstream SIRT1/2/3-MnSOD/PGC-1α pathways. Conclusion: The study finds that the mitochondrial protective effects of PNGL are associated with the NAMPT-SIRT1/2/3-MnSOD/PGC-1α signal pathways. PNGL, as a novel candidate drug, has great application prospects for preventing and treating ischemic stroke.

Preventive Effects of Dairy Products on Dementia and Cognitive Decline (유제품의 치매 및 인지기능 저하 예방 효과)

  • Yun, Jeong-hee;Seol, Kuk-Hwan;Yoo, Jayeon;Oh, Mi-Hwa;Ham, Jun-Sang
    • Journal of Dairy Science and Biotechnology
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    • 제38권1호
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    • pp.27-36
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    • 2020
  • The prevention of cognitive decline and dementia is an increasingly important global public health priority due to an increase in the percentage of the elderly population. Dementia, a severe cognitive disorder, not only negatively impacts the patients' quality of life but also creates a substantial burden for caregivers. This review introduced recent advances regarding the protective effects of dairy product intake against dementia and cognitive decline. Recent epidemiological studies have suggested that specific components of dairy products including bioactive peptides, colostrinin, proline-rich polypeptides, α-lactalbumin, vitamin B12, calcium, and probiotics might promote healthy brain function during aging. Additionally, oleamide and dehydroergosterol in Camembert cheese have been suggested as agents capable of reducing microglial inflammatory responses and neurotoxicity. The intake of neuroprotective and anti-inflammatory compounds in meals is safe and easy, hence nutritional approaches, including dairy product consumption, serve as a promising intervention for the prevention of neurodegenerative disorders.

Terpenes from Forests and Human Health

  • Cho, Kyoung Sang;Lim, Young-ran;Lee, Kyungho;Lee, Jaeseok;Lee, Jang Ho;Lee, Im-Soon
    • Toxicological Research
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    • 제33권2호
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    • pp.97-106
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    • 2017
  • Forest bathing has beneficial effects on human health via showering of forest aerosols as well as physical relaxation. Terpenes that consist of multiple isoprene units are the largest class of organic compounds produced by various plants, and one of the major components of forest aerosols. Traditionally, terpene-containing plant oil has been used to treat various diseases without knowing the exact functions or the mechanisms of action of the individual bioactive compounds. This review categorizes various terpenes easily obtained from forests according to their anti-inflammatory, anti-tumorigenic, or neuroprotective activities. Moreover, potential action mechanisms of the individual terpenes and their effects on such processes, which are described in various in vivo and in vitro systems, are discussed. In conclusion, the studies that show the biological effectiveness of terpenes support the benefits of forest bathing and propose a potential use of terpenes as chemotherapeutic agents for treating various human diseases.

Sea Buckthorn (Hippophae rhamnoides L.) Leaf Extracts Protect Neuronal PC-12 Cells from Oxidative Stress

  • Cho, Chi Heung;Jang, Holim;Lee, Migi;Kang, Hee;Heo, Ho Jin;Kim, Dae-Ok
    • Journal of Microbiology and Biotechnology
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    • 제27권7호
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    • pp.1257-1265
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    • 2017
  • The present study was carried out to investigate the antioxidative and neuroprotective effects of sea buckthorn (Hippophae rhamnoides L.) leaves (SBL) harvested at different times. Reversed-phase high-performance liquid chromatography analysis revealed five major phenolic compounds: ellagic acid, gallic acid, isorhamnetin, kaempferol, and quercetin. SBL harvested in August had the highest total phenolic and flavonoid contents and antioxidant capacity. Treatment of neuronal PC-12 cells with the ethyl acetate fraction of SBL harvested in August increased their viability and membrane integrity and reduced intracellular oxidative stress in a dose-dependent manner. The relative populations of both early and late apoptotic PC-12 cells were decreased by treatment with the SBL ethyl acetate fraction, based on flow cytometry analysis using annexin V-FITC/PI staining. These findings suggest that SBL can serve as a good source of antioxidants and medicinal agents that attenuate oxidative stress.

Antidotal and Neuroprotective Efficacies of a Prophylactic Patch against Sarin and Soman Poisonings in Guinea Pigs (신경작용제 사린 및 소만 중독에 대한 기니픽에서의 예방패치의 해독 및 뇌보호 효능)

  • Song, Youngjo
    • Journal of the Korea Institute of Military Science and Technology
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    • 제24권1호
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    • pp.144-150
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    • 2021
  • This study was designed to evaluate the prophylactic efficacy of a combinational patch system containing physostigmine and procyclidine against sarin and soman using guinea pig. The median lethal dose values of two nerve agents were calculated by a probit analysis of deaths occurring within 24 h. In this study, the values of median lethal dose of sarin and soman were determined to be 33.0 and 26.7 ㎍/kg in guinea-pigs, respectively. The guinea pigs treated with a prophylactic patch(4×5 ㎠) for 24 h were 100 % protected against a challenge of 1.5 LD50. The combinational KMARK-1(atropine and 2-PAM) and prophylactic patch were more effective than a single KMARK-1, a combination of pyridostigmine and KMARK-1 significantly. Epileptiform seizures in the guinea pigs treated with the combinational antidotes led to neuropathological changes, in comparison with intact feature of brain of the animal treated with the patch.

The effects of Gagambosim-Tang of focal brain ischemic injury induced by Intraluminal Filament insertion in the rats (가감보심탕(加減補心湯)의 구강투여가 Intraluminal Filament 삽입술(揷入術)에 의(依)해 유발(誘發)된 백서(白鼠)의 허혈성(虛血性) 뇌손상(腦損傷)에 미치는 영향(影響))

  • Ryu, Seung-Jun;Lee, Chung-Sik;Park, Bo-Ra;Seo, Jong-Hoon;Kang, Hyung-Won;Lyu, Yeong-Su;Kim, Tae-Heon
    • Journal of Oriental Neuropsychiatry
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    • 제18권1호
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    • pp.153-171
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    • 2007
  • Objective : The aim of this study was to investigate effects of Gagambosim-Tang(GBT) of focal brain ischemic injury induced by intraluminal filament insertion in the rats. Method : The ischemia was induced by intraluminal filament insertion into middle cerebral artery Eight-arm radial maze was designed for the behavioral task. Gagambosim-Tang was orally administrated in SD rats for 21 days. The task was started on the 4th week after focal brain injury, and performed two trials per day for 6days. The effects of Gagambosim-Tang on neuroprotective agents in cresyl violet, choline acetyltranferase(ChAT), nerve growth factor (NGF)-stain and c-Fos with ischemic injury were investigated. Results : The errors in the eight-arm radial maze task were significantly decreased in normal group compared with control group on 2-6days, GBT lX(42.2 mg/ml)orally administrated group on 1days, GBT 6X(253.2 mg/ml) on 3, 5, 6days. The rate of correct choice was increased in normal and GBT 6X groups. The neuroprotective effect in the hippocampal CA1 was increased in normal and GBT 1X, GBT 6X groups compared with control group. The density of ChAT in the hippocampal CA1 was increased in normal and GBT6X groups compared with control group. The density of NGF in the hippocampal CA1 was increased normal and GBT6X groups compared with control group. The number of c-Fos-positive neurons in the hippocampal CA1 was increased in normal and GBT 6X groups compared with control group. Conclusion : These results suggest that Gagambosim-Tang may have protective effect on dementia.

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Antioxidant Activity of Glycyrrhiza uralensis Fisch Extracts on Hydrogen Peroxide-induced DNA Damage in Human Leucocytes and Cell Death in PC12 Cells

  • Lee, Hyun-Jin;Yoon, Mi-Young;Kim, Ju-Young;Kim, Yong-Seong;Park, Hae-Ryong;Park, Eun-Ju
    • Food Science and Biotechnology
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    • 제17권2호
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    • pp.343-348
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    • 2008
  • In this study, antioxidant activity of methanol extract of Glycyrrhiza uralensis Fisch (GUE) against $H_2O_2$-induced DNA damage in human leucocytcs and cell death in PC12 cells was determined. The effect of GUE on $H_2O_2$-induced DNA damage in human leucocytcs was evaluated by the comet assay, where GUE ($1-50\;{\mu}g/mL$) was a dose dependent inhibitor of DNA damage induced by $H_2O_2$. The protective effect of GUE against $H_2O_2$-induced damage on PC12 cells was investigated by MTT reduction assay and lactate dehydrogenase release assay. A marked reduction in cell survival induced by $H_2O_2$ was significantly prevented by $1-50\;{\mu}g/mL$ of GUE. The enzyme activity of caspase-3 was elevated in $H_2O_2$-treated PC12 cells, while preincubation with GUE for 30 min inhibited $H_2O_2$-induced caspase-3 activation in a dose-dependent manner. In conclusion, GUE ameliorates $H_2O_2$-induced DNA damage in human leucocytes and has neuroprotective effect by preventing cell death in PC12 cell, suggesting that GU may be a potential candidate for novel therapeutic agents for neuronal diseases associated with oxidative stress.

Phellodendron amurense and Its Major Alkaloid Compound, Berberine Ameliorates Scopolamine-Induced Neuronal Impairment and Memory Dysfunction in Rats

  • Lee, Bom-Bi;Sur, Bong-Jun;Shim, In-Sop;Lee, Hye-Jung;Hahm, Dae-Hyun
    • The Korean Journal of Physiology and Pharmacology
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    • 제16권2호
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    • pp.79-89
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    • 2012
  • We examine whether Phellodendron amurense (PA) and its major alkaloid compound, berberine (BER), improved memory defects caused by administering scopolamine in rats. Effects of PA and BER on the acetylcholinergic system and pro-inflammatory cytokines in the hippocampus were also investigated. Male rats were administered daily doses for 14 days of PA (100 and 200 mg/kg, i.p.) and BER (20 mg/kg, i.p.) 30 min before scopolamine injection (2 mg/kg, i.p.). Daily administration of PA and BER improved memory impairment as measured by the passive avoidance test and reduced the escape latency for finding the platform in the Morris water maze test. Administration of PA and BER significantly alleviated memory-associated decreases in cholinergic immunoreactivity and restored brain-derived neurotrophic factor and cAMP-response element-binding protein mRNA expression in the hippocampus. PA and BER also decreased significantly the expression of proinflammatory cytokines such as interleukin-$1{\beta}$, tumor necrosis factor-${\alpha}$ and cyclooxygenase-2 mRNA in the hippocampus. These results demonstrated that PA and BER had significant neuroprotective effects against neuronal impairment and memory dysfunction caused by scopolamine in rats. These results suggest that PA and BER may be useful as therapeutic agents for improving cognitive functioning by stimulating cholinergic enzyme activity and alleviating inflammatory responses.

Photochemically Induced Cerebral Ischemia in a Mouse Model

  • Park, Sung-Ku;Lee, Jung-Kil;Moon, Kyung-Sub;Joo, Sung-Pil;Kim, Jae-Hyoo;Kim, Soo-Han
    • Journal of Korean Neurosurgical Society
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    • 제40권3호
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    • pp.180-185
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    • 2006
  • Objective : Middle cerebral artery occlusion[MCAO] has widely been used to produce ischemic brain lesions. The lesions induced by MCAO tend to be variable in size because of the variance in the collateral blood supply found in the mouse brain. To establish a less invasive and reproducible focal ischemia model in mice, we modified the technique used for rat photo thrombosis model. Methods : Male C57BL/6 mice were subjected to focal cerebral ischemia by photothrombosis of cortical microvessels. Cerebral infarction was produced by intraperitoneal injection of Rose Bengal, a photosensitive dye and by focal illumination through the skull. Motor impairment was assessed by the accelerating rotarod and staircase tests. The brain was perfusion-fixed for histological determination of infarct volume four weeks after stroke. Results : The lesion was located in the frontal and parietal cortex and the underlying white matter was partly affected. A relatively constant infarct volume was achieved one month after photothrombosis. The presence of the photothrombotic lesion was associated with severe impairment of the motor performance measured by the rotarod and staircase tests. Conclusion : Photothrombotic infarction in mice is highly reproducible in size and location. This procedure can provide a simple method to produce cerebral infarction in a unilateral motor cortex lesion. In addition, it can provide a suitable model for study of potential neuroprotective and therapeutic agents in human stroke.