• Journal of Environmental Health Sciences
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• v.22 no.3
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• pp.8-16
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• 1996

Effects of water extract of aloe vera on lead-induced neurotoxicity were investigated in sciatic nerve isolated from rat. The mechanism on toxicity reduction by measuring activities of axonal enzymes, metabolism of myo-inositol in nerve, lead concentration in several organs and so on were further examimed. In the lead-treated rats, the transport rate of axonal enzyme, such as acetyl cholinesterase and choline acetyltransferase, was reduced by from 50% to 30% respectively. Reduction in myo-inositol concentration and $Na^+/K^+$ ATPase activity were also observed in sciatic nerve from lead-treated rat. However, the aloe extract administration significantly eliminated the impairment and maintained myo-inositol concentration to about 85% of normal level. Also aloe extract promoted the excretion rate of lead which is accumulated in blood, sciatic nerve and kidney. These results suggest that lead-induced neurotoxicity was significantly reduced by administration of aloe extract and the mechanism might be partly increase in kidney excretion rate of lead and parity normalization of $Na^+/K^+$ ATPase activity which is critical factor in order to keep nerve maintaining normal myo-inositol level.

• Biomolecules & Therapeutics
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• v.28 no.5
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• pp.381-388
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• 2020

Methamphetamine (METH) is a highly addictive psychostimulant and one of the most widely abused drugs worldwide. The continuous use of METH eventually leads to drug addiction and causes serious health complications, including attention deficit, memory loss and cognitive decline. These neurological complications are strongly associated with METH-induced neurotoxicity and neuroinflammation, which leads to neuronal cell death. The current review investigates the molecular mechanisms underlying METH-mediated neuronal damages. Our analysis demonstrates that the process of neuronal impairment by METH is closely related to oxidative stress, transcription factor activation, DNA damage, excitatory toxicity and various apoptosis pathways. Thus, we reach the conclusion here that METH-induced neuronal damages are attributed to the neurotoxic and neuroinflammatory effect of the drug. This review provides an insight into the mechanisms of METH addiction and contributes to the discovery of therapeutic targets on neurological impairment by METH abuse.

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.1
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• pp.101-104
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• 2003

It has been suggested that oxidative stress of reactive oxygen species(ROS) may play a key role in the pathogenesis of neuronal complications. The aim of this study was to examine the cytotoxic effect of hydrogen peroxide(H₂O₂) in the cultured mouse cerebral neurons and the protective effect of Schisandrae Fructus(SF) on ROS-induced neurotoxicity. Cytotoxic effect of H₂O₂ and neuroprotective effect of SF were determined by MTT assay. H₂O₂ decreased cell viability in dose-and time-dependent mannner, and SF decreased H₂O₂-induced neurotoxicity in these cultures. From above the results, H₂O₂ has toxic effect, and herb extract, SF is very effective against H₂O₂-induced neurotoxicity in cultured cerebral neurons of mouse.

• Biomolecules & Therapeutics
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• v.22 no.3
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• pp.176-183
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• 2014

Cognitive impairment is a result of dementia of diverse causes, such as cholinergic dysfunction and Alzheimer's disease (AD). Houttuynia cordata Thunb. (Saururaceae) has long been used as a traditional herbal medicine. It has biological activities including protective effects against amyloid beta ($A{\beta}$) toxicity, via regulation of calcium homeostasis, in rat hippocampal cells. To extend previous reports, we investigated the effects of water extracts of H. cordata herb (HCW) on tauopathies, also involving calcium influx. We then confirmed the effects of HCW in improving memory impairment and neuronal damage in mice with Ab-induced neurotoxicity. We also investigated the effects of HCW against scopolamine-induced cholinergic dysfunction in mice. In primary neuronal cells, HCW inhibited the phosphorylation of tau by regulating p25/p35 expression in $A{\beta}$-induced neurotoxicity. In mice with $A{\beta}$-induced neurotoxicity, HCW improved cognitive impairment, as assessed with behavioral tasks, such as novel object recognition, Y-maze, and passive avoidance tasks. HCW also inhibited the degeneration of neurons in the CA3 region of the hippocampus in Ab-induced neurotoxicity. Moreover, HCW, which had an $IC_{50}$ value of $79.7{\mu}g/ml$ for acetylcholinesterase inhibition, ameliorated scopolamine-induced cognitive impairment significantly in Y-maze and passive avoidance tasks. These results indicate that HCW improved cognitive impairment, due to cholinergic dysfunction, with inhibitory effects against tauopathies and cholinergic antagonists, suggesting that HCW may be an interesting candidate to investigate for the treatment of AD.

• Natural Product Sciences
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• v.18 no.1
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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.

• Archives of Pharmacal Research
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• v.24 no.2
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• pp.164-170
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• 2001

Glutamate receptors-mediated excitoxicity is believed to play a role in the pathophysiology of neurodegenerative diseases. The present study was performed to evaluate the inhibitory effect of fanschinoline, a bis-benzylisoquinoline alkaloid, which has a characteristic as a $Ca^{2+}$channel blockers on excitatory amino acids (EAAS)-induced neurotoxicity in cultured rat cerebellar granule neuron. Fangchinoline (1 and 5$\mu\textrm{m}$) inhibited glutamate (1 ${m}M$), N-methyl-D-aspartate (NMDA; 1 ${m}M$) and kainate (100$\mu\textrm{m}$)-induced neuronal cell death which was measured by trypan blue exclusion test. Fangchinoline (1 and 5$\mu\textrm{m}$) inhibited glutamate release into medium induced by NMDA (1 ${m}M$) and kainate (100$\mu\textrm{m}$), which was measured by HPLC. And fangchinoline (5$\mu\textrm{m}$) inhibited glutamate (1 ${m}M$)-induced elevation of intracellular calcium concentration. These results suggest that inhibition of $Ca^{2+}$influx by fangchinoline may contribute to the beneficial effects on neurodegenerative effect of glutamate in pathophysiological conditions.

• Korean Journal of Clinical Laboratory Science
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• v.50 no.4
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• pp.501-510
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• 2018

This study examined the neurotoxicity induced by lead acetate (LA) on cultured C6 glioma cells and the protective effects of Euphorbiae humifusae L. (EH) extract against LA-induced cytotoxicity. In this study, LA exhibited neurotoxicity in a dose-dependent manner compared to the control, and was determined to be highly-toxic according to the toxic criteria. The $XTT_{50}$ value of LA was calculated at a concentration of $38.6{\mu}M$ after C6 glioma cells were incubated for 72 hours in the media containing $30{\sim}50{\mu}M$ of LA, respectively. In addition, LA-induced neurotoxicity was suggested to correlate with the level of oxidative stress because vitamin E, an antioxidant, increased the cell viability damaged by LA-induced cytotoxicity. The EH extract effectively prevented cell injury from LA-induced cytotoxicity via its antioxidative effects, such as inhibitory ability of lipid peroxidation, superoxide dismutase-like activity and 1,1-diphenyl-2-picrylhydrazyl-radical scavenging activity. These antioxidative effects may result in components, such as polyphenol or flavonoids including gallic acid or quercetin. In conclusion, natural resources, such as EH extracts, may be a useful putative agent for the treatment of diseases associated with oxidative stress, such as lead neurotoxicity.

• Proceedings of the PSK Conference
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• 2003.10a
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• pp.112-112
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• 2003

Morphine is a potent analgesic and addictive substance. Morphine produces neurotoxicity such as rewarding effect, analgesic tolerance and physical dependence. It has been restricted to the use of morphine in patients because of these problems. The present study was investigated the effect of berberine on the neurotoxicity of morphine. Repeated administration of morphine produced conditioned place prefernece (CPP) and behavioral sensitization in mice. (omitted)

• Journal of Ginseng Research
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• v.33 no.4
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• pp.294-304
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• 2009

Ginsenosides are among the most well-known traditional herbal medicines frequently used for the treatment of various symptoms in South Korea. The neuroprotective effects of ginsenoside $Rg_3$ (G-$Rg_3$) on cholesterol-oxide-(CO)-induced neurotoxicity were investigated through the analyses of rat brains. The recently accumulated reports show that ginseng saponins (GTS), the major active ingredients of Panax ginseng, have protective effects against neurotoxin insults. In the present study, the neuroprotective effects of G-$Rg_3$ on CO-induced hippocampal excitotoxicity were examined in vivo. The in-vitro studies using rat cultured hippocampal neurons revealed that G-$Rg_3$ treatment significantly inhibited CO-induced hippocampal cell death. G-$Rg_3$ treatment not only significantly reduced CO-induced DNA damage but also attenuated CO-induced apoptosis. The in-vivo studies that were conducted revealed that the intracerebroventricular (i.c.v.) pre-administration of G-$Rg_3$ significantly reduced i.c.v. CO-induced hippocampal damage in rats. To examine the mechanisms underlying the in-vitro and in-vivo neuroprotective effects of G-$Rg_3$ against CO-induced hippocampal excitotoxicity, the effect of G-$Rg_3$ on the CO-induced elevations of the apoptotic cells in cultured hippocampal cells was examined, and it was found that G-$Rg_3$ treatment inhibited CO-induced apoptosis. The histopathological evaluation demonstrated that G-$Rg_3$ significantly diminished the apoptosis in the hippocampus and also spared the hippocampal CA1, CA3, and dentate gyrus neurons. G-$Rg_3$ also significantly improved the CO-caused behavioral impairment. G-$Rg_3$ itself had no effect, however, on the CO-induced inhibition of succinate dehydrogenase activity (data not shown). These results collectively indicate the G-$Rg_3$-induced neuroprotection against CO in rat hippocampus. With regard to the wide use of G-$Rg_3$, this agent is potentially beneficial in treating CO-induced brain injury.

• YAKHAK HOEJI
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• v.41 no.1
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• pp.99-104
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• 1997

In order to elucidate the cytotoxic effect of oxygen radicals on cultured spinal dorsal root ganglion(DRG) neurons derived from mouse. the neurotoxic effect of oxygen radicals w as examined after cultured DRG neurons were exposed to xanthine oxidase(XO) and hypoxanthine(HX)-oxygen radical generating system. In addition. neuroprotective effect of epidermal growth factor(EGF) against oxidant-induced neurotoxicity was also evaluated in these cultures. The results were, as follows: 1. Lethal concentration 50(LC$_{50}$) was 35mU/ml XO and 0.1mM HX in cultured DRG neurons. 2. Oxygen radicals induced the morphological changes such as the decrease of cell number and loss of neurites in these cultures. 3. EGF increased the cell viability and neurofilament in neurons damaged by oxygen radicals. From above the results, it is suggested that oxygen radicals have a cytotoxic effect on cultured DRG neurons of neonatal mouse and selective neurotrophic factors such as EGF are, effective, in blocking the neurotoxicity induced by oxygen radicals in cultured spinal DRG neurons.