• Biomolecules & Therapeutics
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• v.3 no.4
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• pp.256-259
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• 1995

Antinociceptive and desensitizing effects of systemically administered capsaicinoids (capsaicin and KR25018) were investigated in guinea pig. Nociceptive sensitivity to chemical stimulus was examined to test sensory function, and the content of substance P-like immunorractivity (SP-LI) in bronchi was determined as a peripheral marker of capsaicin-sensitive primary afferent neurons. Guinea pigs were pretreated s.c. with several doses of capsaicin (1,2.5,5, 10 mg/kg) or KR25018 (1, 2.5, 5, 10 mg/kg) one week prior to the experiments. Frequency of eye wiping was significantly decreased by capsaicin and KR25018 in a pretreatment dosedependent manner. In capsaicin- or KR25018-pretreated guinea pigs, there was a significant loss of SP-LI in bronchial tissue extracts. In summary, a newly synthesized capsaicin analogue H725018 exhibited antinociceptive effect against chemical stimulus in guinea pig, with comparable potency to capsaicin. This desensitizing activity of capsaicin or KR25018 might be related to the loss of SP-LI in peripheral afferent nerves.

• Journal of People, Plants, and Environment
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• v.21 no.6
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• pp.515-521
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• 2018

The purpose of this study was to investigate the effects of horticultural activities with reminiscence materials and singing songs on the ability to recall words and depression in the elderly with mild dementia. A total of 20 sessions of a horticultural therapy program was held once or twice a week from July 14, 2015 to November 3, 2015 for the elderly with mind dementia at the social welfare center in D city. The subjects of this study were 13 women and the mean age was 81.2 years. The ability to recall words significantly improved from $8.6{\pm}1.8$ before the program to $9.4{\pm}0.6$ after the program (p=.012). However, there was no significant difference in the score of depression after the program. Synergistic effects were generated by applying horticultural activities, singing and reminiscence therapy activities simultaneously, and it was effective in recalling memories. As emotional functions were associated with hormones in vivo, there were emotional ups and downs at each session and short-term alternative therapies were not sufficient to completely eliminate neurotoxic substances caused by dementia.

• Herbal Formula Science
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• v.7 no.1
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• pp.143-151
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• 1999

To evaluate the neurotoxic effect of oxygen radicals in cultured mouse spinal dorsal root ganglion(DRG) neurons, cytotoxicity was determined by MTT assay after cultured DRG neurons were grown in the media containing various concentrations of glucose oxidase(GO). In addition, neuroprotective effect of herb extract, Epimedium Koreanum Nakai was examined by MTT assay in cultured DRG neurons. Cell viability of cultured DRG neurons was remarkably decreased by GO in dose- and time-dependent manner, and Epimedium Koreanum Nakai protected remarkably GO-induced neurotoxicity in these cultures. From the above results, it is suggested that oxygen radicals is toxic in cultured mouse DRG neurons, and herb extracts such as Epimedium Koreanum Nakai are effective in prevention of the neurotoxicity induced by oxygen radicals in cultured mouse DRG neurons.

• Toxicological Research
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• v.11 no.1
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• pp.9-14
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• 1995

The immune system is partially under the control of the sympathetic and parasymphathetic nervous systems through the regulatory feedback loop. Methamphetamine (MA) is a neurotoxic chemical which affects the neurotransmitter system. The objective of this study was to investigate the immunotoxic effect of MA on the major immune target organ and lymphocyte proliferation to the various mitogens. Female Balb/C mice, 15 to 20 g, were injected subcutaneously with 0, 0.5, or 5 mg MA/kg for 14 consecutive days. In MA treated mice, the body weight gain and relative spleen and thymus weight were decreased in doserelated manner. Histopathologically, there was a paucity of lymphold follicles and germinal centers in the spleen, and thymic cortical atrophy with lymphophagocytosis was prominent. Apoptosis also occurred in germinal centers of spleen and thymic cortex. The threshold and peak of lymphocyte proliferation at various concentration of mitogens showed similar patterns. However, the response to lipopolysaccaride (LPS) and pokeweed mitogen (PWM) in the 5 mg MA/kg treated group showed threshold and peak proliferation at high concentration of mitogens (25${\mu}g$ LPS/ml for MA vs 15${\mu}g$ LPS/ml for control; 60${\mu}g$ PWM/ml for MA vs 45${\mu}g$ PWM/ml for control), which suggest that MA impairs T cell dependent-B cell function. This preliminary study indicated that MA affected the lymphold organs and immune function.

• Biomolecules & Therapeutics
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• v.19 no.3
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• pp.288-295
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• 2011

Amyloid beta ($A{\beta}$)-induced neurotoxicity is a major pathological mechanism of Alzheimer's disease (AD). In this study, we investigated the inhibitory effect of L-theanine, a component of green tea (Camellia sinensis) on $A{\beta}_{1-42}$-induced neurotoxicity and oxidative damages of macromolecules. L-theanine inhibited $A{\beta}_{1-42}$-induced generation of reactive oxygen species, and activation of extracellular signal-regulated kinase and p38 mitogenic activated protein kinase as well as the activity of nuclear factor kappa-B. L-theanine also signifi cantly reduced oxidative protein and lipid damage, and elevated glutathione level. Consistent with the reduced neurotoxic signals, L-theanine (10-50 ${\mu}g$/ml) concomitantly attenuated $A{\beta}_{1-42}$ (5 ${\mu}M$)-induced neurotoxicity in SK-N-MC and SK-N-SH human neuroblastoma cells. These data indicate that L-theanine on $A{\beta}$-induced neurotoxicity prevented oxidative damages of neuronal cells, and may be useful in the prevention and treatment of neurodegenerative disease like AD.

• Journal of the Korean Society of Tobacco Science
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• v.20 no.1
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• pp.99-107
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• 1998

Numerous studies have demonstrated a negative association between cigarette smoking and Parkinson's disease. The present study was undertaken to investigate whether chronic exposure of mice to cigarette smoke a(footed the metabolism of 1-methyl-1113,6-tetrahydro-pyridine (MPTP) by cytochrome P4SO (P-450) or flavin-containing monooxygenase (FMO) in the hepatic microsomes of C57BL6/J mice. Adult male C57BL6/J mice were exposed to mainstream smoke generated from 15 cigarettes for 10 min a day and 5 day per week for 6 weeks. MPTP (10 mg/kg body weight) was administered to mice by subcutaneous injection for 6 consecutive days. Microsolnal P-450 content was increased by MPTP, smoke exposure, or both, but NADPH cytochrome P-450 reductase activity was rather decreased by the same treatments. The activities of benzo(a)pyrene hydroxylase, 7-ethoxycoumarin O-deethylase and ethoxyresorufin O-deethylase were significantly increased by the exposure of cigarette smoke, but were not or little affected by MPTP treatment. Benzphetamine N-demethylase activity was not affected either by MPTP treatment or by cigarette smoke exposure, but it was significantly increased by the combined MPTP treatment with cigarette smoke exposure, showing their synergic effect for the induction of the enzyme activity. Interestingly, in vitro studies of hepatic FMO and P-450 system both O-oxygenation and N-demethylation of MPTP were increased in the smoke-exposed or in the MPTP-treated mice. These results suggest that the enhancement in the N-demethylation as well as O-deethylation of P-450 system and in the N-oxygenation of FMO activity by cigarette smoke exposure in mouse liver may contribute to attenuating the neurotoxic effects of MPTP on the nigrostriatal dopaminergic neurons.

• The Journal of Korea CHUNA Manual Medicine
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• v.2 no.1
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• pp.143-157
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• 2001

Objectives and Methods : To evaluate the mechanism of oxidative damage by xanthine oxydase(XO) and hypoxanthine(HX)-induced oxygen radicals, MTT assay and NR assay were carried out after the cultured mouse spinal sensory neurons were preincubated for 4 hours with various concentrations of XO/HX. And the amount of total protein. neurofilament EIA. lipid peroxidation and LDH activity were measured, to evaluate the protective effect of Herbar Chelidonii(HC) water extract on cultured spinal sensory neurons damaged by XO/HX. after the cultured mouse spinal sensory neurons were preincubated with various concentrations of HC water extract for 3 hours prior to exposure of XO/HX. Results : XO/HX decreased significantly the survival rate of the cultured mouse sensory neurons by NR assay and MTT assay In proportion to concentration and exposed time. In proportion to concentration and exposed time on cultured spinal sensory neurons, XO/HX showed the quantitative decrease of neurofilament by EIA. the decrease of total protein amount by SRB assay and the Increase of lipid peroxidation as well as LDH. HC showed the quantitative increase of neurofilament and total protein, but showed the decrease of lipid peroxidation and LDH activity against the neurotoxicity of XO/HX. Conclusions : From the above results, it is concluded that XO/HX have a neurotoxic effect on cultured spinal sensory neurons and that the herbs extract, such as HC, prevent the toxicity of XO/HX effectively in that they decrease lipid peroxidation and LDH activity.

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.2
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• pp.374-379
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• 2003

To evaluate the mechanism of oxidative damage by Xanthine oxidase(XO) and hypoxanthine(HX)-induced oxygen radicals, XTT assay was carried out. Neurofilament EIA and PKC activity were measured to evaluate the protective effect of Jingansikpung-tang(JST) and Gamijingansikpung-tang(GJST) water extract on cultured spinal sensory neurons damaged by XO/HX, after the cultured mouse spinal sensory neurons were preincubated with various concentrations of JST and GJST water extract for 3 hours prior to exposure of XO/HX. The results were XO/HX decreased significantly, in proportion to concentration and exposed time, the survival rate of the cultured mouse sensory neurons on XTT assay. And in proportion to concentration and exposed time on cultured spinal sensory neurons, XO/HX showed the quantitative decrease of neurofilament by EIA, increase of PKC activity, but JST and GJST showed the neuroprotective effects against decrease of neurofilament and increase of PKC activity by XO/HX. From the above results, it is concluded that XO/HX have a neurotoxic effect on cultured spinal sensory neurons and the herbs water extract, such as JST and GJST prevent the toxicity of XO/HX effectively.

• The Korean Journal of Food And Nutrition
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• v.33 no.3
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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.

• Toxicological Research
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• v.6 no.2
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• pp.205-213
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• 1990

The regulation of neurotoxicants has usually been based upon setting reference doses by dividing a no observed adverse effect level (NOAEL) by uncertainty factors that theoretically account for interspecies and intraspecies extraploation of experimental results in animals to humans. Recently, we have proposed a four-step alternative procedure which provides quantitative estimates of risk as a function of dose. The first step is to establish a mathematical relationship between a biological effect or biomarker and the dose of chemical administered. The second step is to determine the distribution (variability) of individual measurements of biological effects or their biomarkers about the dose response curve. The third step is to define an adverse or abnormal level of a biological effect or biomarker in an untreated population. The fourth and final step is to combine the information from the first three steps to estimate the risk (proportion of individuals exceeding on adverse or abnormal level of a biological effect or biomarker) as a function of dose. The primary purpose of this report is to enhance the certainty of the first step of this procedure by improving our understanding of the relationship between a biomarker and dose of administered chemical. Several factors which need to be considered include: 1) the pharmacokinetics of the parent chemical, 2) the target tissue concentrations of the parent chemical or its bioactivated proximate toxicant, 3) the uptake kinetics of the parent chemical or metabolite into the target cell(s) and/or membrane interactions, and 4) the interaction of the chemical or metabolite with presumed receptor site(s). Because these theoretical factors each contain a saturable step due to definitive amounts of required enzyme, reuptake or receptor site(s), a nonlinear, saturable dose-response curve would be predicted. In order to exemplify this process, effects of the neurotoxicant, methlenedioxymethamphetamine (MDMA), were reviewed and analyzed. Our results and those of others indicate that: 1) peak concentrations of MDMA and metabolites are ochieved in rat brain by 30 min and are negligible by 24 hr, 2) a metabolite of MDMA is probably responsible for its neurotoxic effects, and 3) pretreatment with monoamine uptake blockers prevents MDMA neurotoxicity. When data generated from rats administerde MDMA were plotted as bilolgical effect (decreases in hippocampal serotonin concentrations) versus dose, a saturation curve best described the observed relationship. These results support the hypothesis that at least one saturable step is involved in MDMA neurotoxicity. We conclude that the mathematical relationship between biological effect and dose of MDMA, the first step of our quantitative neurotoxicity risk assessment procedure, should reflect this biological model information generated from the whole of the dose-response curve.