• Journal of Life Science
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• v.26 no.4
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• pp.475-483
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• 2016

The current study was conducted to evaluate beneficial effects of a new formula (CWC-9) using four traditional Oriental medicinal herbs, Cynanchum wilfordii, Rehmannia glutinosa, Polygala tenuifolia, and Acorus gramineus, on hippocampal cells and memory function. To examine the neuroprotective effects of a new four-herb extract, cell viability, cytotoxicity, and reactive oxygen species (ROS) assays were performed in HT22 cells and behavioral tests (Morris water maze and passive avoidance retention), Western blot, and immunohistochemistry were performed in a mouse model of focal cerebral ischemia. In HT22 hippocampal cells, pretreatment with CWC-9 resulted in significantly reduced glutamate-induced cell death with suppression of ROS accumulation caused by glutamate. In a mouse model of focal cerebral ischemia, we observed significant improvement of spatial and short-term memory function by treatment with CWC-9. Phosphorylated p38 mitogen-activated protein kinases (MAPK) in hippocampus of ischemic mice were decreased by treatment with CWC-9, but phosphorylated phosphatidylinositol-3 kinase (PI3K) and cAMP response element binding protein (CREB) were significantly enhanced. By immunohistochemical analysis, we confirmed higher expression of phosphorylation of CREB in the hippocampal neurons of CWC-9 treated mice. These results suggest that new multi-herb formula CWC-9 mainly exerted beneficial effects on cognitive function through regulation of neuro-protective signaling pathways associated with CREB.

• The Journal of Korean Medicine
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• v.35 no.4
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• pp.10-23
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• 2014

Objectives: This study evaluated the effects of Guibi-tang (GBT) on neuronal apoptosis and cognitive impairment induced by beta amyloid ($A{\beta}$), (1-42) injection in the hippocampus of ICR mice. Methods: $A{\beta}$ (1-42) was injected unilaterally into the lateral ventricle using a Hamilton syringe and micropump ($2{\mu}g/3{\mu}{\ell}$, $0.6{\mu}{\ell}/min$). Water extract of GBT was administered orally once a day (500 mg/kg) for 3 weeks after the $A{\beta}$ (1-42) injection. Acquisition of learning and retention of memory were tested using the Morris water maze. Neuronal damage and $A{\beta}$ accumulation in the hippocampus was observed using cresyl violet and Congo red staining. The anti-apoptotic effect of GBT was evaluated using TUNEL labeling in the hippocampus. Results: GBT significantly shortened the escape latencies during acquisition training trials. GBT significantly increased the number of target headings to the platform site, the swimming time spent in the target quadrant, and significantly shortened the time for the 1st target heading during the retention test trial. GBT significantly attenuated the reduction in thickness and number of CA1 neurons, and $A{\beta}$ accumulation in the hippocampus produced by $A{\beta}$ (1-42) injection. GBT significantly reduced the number of TUNEL-labeled neurons in the hippocampus. Conclusion: These results suggest that GBT improved cognitive impairment by reducing neuronal apoptosis and $A{\beta}$ accumulation in the hippocampus. GBT may be a beneficial herbal formulation in treating cognitive impairment including Alzheimer's disease.

• Korean Journal of Biological Psychiatry
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• v.6 no.2
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• pp.193-201
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• 1999

This study was designed to evaluate the effects of opioid receptor agonists on the spontaneous alternation behaviour in an animal model of obsessivecompulsive disorder in rats. According to the theory that dopamine is related to the biological etiology of obsessive-compulsive disorder, the effect of the nalbuphine(opioid kappa agonist) and the tramadol(opioid mu agonist), which act as manipulating agents on the inhibition or stimulation of dopamine release, in the spontaneous alternation behaviour were evaluated. 24 hours prior to the experiment, rats were food-deprived. These rats were put into the T-maze, in which white and black goal boxes were baited with small amounts of chocolate milk. Each rat was given 2 set of 7 trials during which it was placed in the start box and allowed to choose the one of the goal boxes for each time. After identifying the stable baseline of spontaneous alternation behaviour, nonselective 5-HT agonist 5-MeODMT(1.25mg/kg/IP) disrupted spontaneous alternation. Rats were stratified into fluoxetine(10mg/kg/IP), nalbuphine(10mg/kg/IP), tramadol(46.4mg/kg/IP), and saline(0.5cc/IP) injection group with experimental drug treatment for 21 days. The effects on the 5-MeODMT(1.25mg/kg/IP) induced disruption of spontaneous alternation behaviour were checked at the next day of discontinuation of drug treatment. The results were as follows ; 1) At the day after 21 days of the drug treatment, the nalbuphine treated group and the fluoxetine treated group showed significant difference from the tramadol treated group and the saline treated group in the 5-MeODMT(1.25mg/kg/IP) induced suppression of spontaneous alternation behaviour. 2) Within each drug treatment group, the fluoxetine treated group showed significant difference between before and after the treatment of fluoxetine in the 5-MeODMT(1.25mg/kg/IP) induced suppression of spontaneous alternation behaviour. And also, the nalbuphine treated group showed significant difference between before and after the treatment of nalbuphine in the 5-MeODMT(1.25mg/kg/IP) induced suppression of spontaneous alternation behaviour. There was no difference between the baseline and after the treatment of nalbuphine in the 5-MeODMT(1.25mg/kg/IP) induced suppression of spontaneous alternation behaviour. We indentified that the opioid kappa agonist that act as dopamine release inhibitor affect the spontaneous alternation behaviour which is an animal model of obsessive-compulsive disorder in rat.

• Journal of Oriental Neuropsychiatry
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• v.19 no.3
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• pp.69-84
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• 2008

Objective: This experiment was designed to investigate the effects of the KBHT hot water extract & ultra-fine powder on Alzheimer's Disease Model Induced by $\beta$A. Method: The effects of the KBHT hot water extract on expression of proinflammatory cytokine mRNA in BV2 microglial celll cell line treated by lipopolysacchaide(LPS). The effects of the KBHT hot water extract & ultra-fine powder on (1) the behavior (2) AChE in serum (3) the infarction area of the hippocampus, and brain tissue injury in Alzheimer's diseased mice induced with $\beta$A were investigated. Results: 1. The KBHT hot water extract suppressed the expression of proinflammatory cytokine mRNA in BV2 microglial cell line treated with LPS. 2. The KBHT hot water extract & ultra-fine powder a significant inhibitory effect on the memory deficit was shown for the mice with Alzheimer's disease induced by $\beta$A in the Morris water maze experiment, which measured stop-through latency and distance movement-through latency 3. The KBHT hot water extract & ultra-fine powder suppressed the over-expression of AChE activity in the serum of the mice with Alzheimer's disease induced by $\alpha$A. 4. The KBHT hot water extract & ultra-fine powder suppressed the expression of TNF-$\alpha$, IL-l$\beta$ protein significantly in the microglial cell of mice with Alzheimer's disease induced by 1$\beta$A. 5. The KBHT ultra-fine powder reduced infarction area of hippocampus significantly in the mice with Alzheimer's disease induced by $\beta$A. Conclusions: These results suggest that the KBHT hot water extract & ultra-fine powder may be effective for the prevention and treatment of Alzheimer's disease. Investigation into the clinical use of the PMCMT hot water extract & ultra-fine powder for Alzheimer's disease is suggested for future research.

• Biomolecules & Therapeutics
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• v.23 no.2
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• pp.156-164
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• 2015

Alzheimer's disease (AD) is a neurodegenerative disorder associated with progressive memory loss and neuronal cell death. Although numerous previous studies have been focused on disease progression or reverse pathological symptoms, therapeutic strategies for AD are limited. Alternatively, the identification of traditional herbal medicines or their active compounds has received much attention. The aims of the present study were to characterize the ameliorating effects of spinosin, a C-glucosylflavone isolated from Zizyphus jujuba var. spinosa, on memory impairment or the pathological changes induced through amyloid-${\beta}_{1-42}$ oligomer ($A{\beta}O$) in mice. Memory impairment was induced by intracerebroventricular injection of $A{\beta}O$ ($50{\mu}M$) and spinosin (5, 10, and 20 mg/kg) was administered for 7 days. In the behavioral tasks, the subchronic administration of spinosin (20 mg/kg, p.o.) significantly ameliorated $A{\beta}O$-induced cognitive impairment in the passive avoidance task or the Y-maze task. To identify the effects of spinosin on the pathological changes induced through $A{\beta}O$, immunohistochemistry and Western blot analyses were performed. Spinosin treatment also reduced the number of activated microglia and astrocytes observed after $A{\beta}O$ injection. In addition, spinosin rescued the $A{\beta}O$-induced decrease in choline acetyltransferase expression levels. These results suggest that spinosin ameliorated memory impairment induced through $A{\beta}O$, and these effects were regulated, in part, through neuroprotective activity via the anti-inflammatory effects of spinosin. Therefore, spinosin might be a useful agent against the amyloid ${\beta}$ protein-induced cognitive dysfunction observed in AD patients.

• Journal of Nutrition and Health
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• v.2 no.4
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• pp.113-125
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• 1969

These experiments were designed to study the influence of early protein undernutrition on growth, behaviors toward food, general attitude toward a new environment, brain size and body composition of the experimental rats. The following experimental groups were studied. Lactation period (3 weeks) (Diets of mother rats) 25% Casein diet 12% Casein diet 25% Casein diet 25% Casein diet 12% Casein diet 12% Casein diet After-weaning protein deprivation period None deprivation (25% Casein diet) None deprivation (25% Casein diet) 5% Casein diet (4 weeks) 5% Casein diet (8 weeks) 5% Casein diet (4 weeks) 5% Casein diet (8 weeks) After a long period of rehabilitation with 25% casein diet the following results were obtained. 1. Growth rate during lactation period is closely related with the protein levels of the diet for mother rats. The average body weight of offsprings of the mother rat fed 25% casein diet is 46.0 grams at 21 days old. However, that of the mother rat fed 12% casein diet is only 25.0 grams. 2. The group of protein undernutrition during lactation (S weeks) (offsprings of mother rat fed low protein diet, 12% casein diet) could never catch up with the normal group in its growth even after twenty-four (24) weeks of rehabilitation. 3. However, the groups of protein undernutrition during either four (4) or even eight (8) weeks after weaning could catch up with the normal group in their growth after long period of rehabilitation. 4. The absolute amounts of carcass protein and fat of the normal group are larger than those of the protein deficient groups. In terms of percent carcass, however, the normal group showed higher body fat and lower body protein than the early deficient groups. However, there is no difference between preweaning (3 weeks) and postweaning (8 weeks) deficient groups. It is assumed, from these differences in body composition, that there might be any differences in physiological and metabolic functions among these various groups, and also that the basic formation of various metabolic regulators (protein-nature) might be fixed mostly during lactation and postweaning period. 5. The groups of protein undernutrition during either three (3) weeks lactation or four (4) weeks after weaning are not so remarkably different from the normal group in their amounts of food intake and spillage. However, the groups of undernutrition during either eight (8) weeks postweaning or eleven (11) weeks (3 weeks lactation period plus 8 weeks postweaning period) showed higher amounts of food intake and spillage. In these respects, it seems that desire for food is closely related with the degree of early hunger in protein and also seems that the longer be deficient in early life the more food spillage is found. 6. Both preweaning and postweaning deficient groups showed generally nervous and restless. The normal group is staid and showed less mobilities. 7. The average size of the brains of the group subjected to protein deficiency during three (3) weeks lactation period is smaller than that of the group of the eight (8) weeks postweaning deficiency. This means that the development of the brain is made mostly during lactation period. The group of the eleven (11) weeks postnatal deficiency is significantly different from the normal group in its brain development. It is assumed, in connection with the results of various maze tests reported, that the brain size is closely related with the intellectual ability.

• The Journal of Korean Medicine
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• v.30 no.3
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• pp.1-14
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• 2009

Objectives : Alzheimer's disease (AD) is characterized by neuronal loss and extracellular senile plaque. Moreover, the cellular actions of ${\beta}$-amyloid (A${\beta}$ play a causative role in the pathogenesis of AD. This study was designed to determine whether Woo-Gui-Um, a commonly used Korean herbal medicine, has the ability to protect cortical and hippocampal neurons against A${\beta}_{25-35}$ neurotoxicity Methods : In the present study, the authors investigated the preventative effects of the water extract of Woo-Gui-Um in a mouse model of AD. Memory impairment was induced by intraventricularly (i.c.v.) injecting A${\beta}_{25-35}$ peptides into mice. Woo-Gui-Um extract was then administered orally (p.o.) for 14 days. In addition, A${\beta}_{25-35}$ toxicity on the hippocampus was assessed immunohistochemically, by staining for Tau, MAP2, TUNEL, and Bax, and by performing an in vitro study in PC12 cells. Results : Woo-Gui-Um extract had an effect to improve learning ability and memory score in the water maze task. Woo-Gui-Um extract had significant neuroprotective effects in vivo against oxidative damage and apoptotic cell death of hippocampal neurons caused by i.c.v. A${\beta}_{25-35}$. In addition, Woo-Gui-Um extract was found to have a protective effect on A${\beta}_{25-35}$-induced apoptosis, and to promote neurite outgrowth of nerve growth factor (NGF)-differentiated PC12 cells. Conclusions : These results suggest that Woo-Gui-Um extract reduces memory impairment and Alzheimer's dementia via an anti-apoptotic effect and by regulating Tau and MAP2 in the hippocampus.

• Journal of Oriental Neuropsychiatry
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• v.22 no.2
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• pp.107-128
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• 2011

Objectives : This experiment was designed to investigate the efficacy of DDTCMT hot water extract & ultra-fine powder on Alzheimer's Disease Model. Methods : The effects of the DDTCMT hot water extract on expression of IL-$1{\beta}$, IL-6, TNF-${\alpha}$, COX-2, NOS-II, IL-10, IL-1 receptor antagonist mRNA and production of IL-$1{\beta}$, IL-6, TNF-${\alpha}$ in BV2 microglial cell line treated by lipopolysacchaide(LPS) were investigated. Expression of NO, ROS in BV2 microglial cell line treated by LPS and AChE activity in PC-12 cell treated by NGF were investigated. anti-AChE was observed through Western blot analysis. The effects of the DDTCMT hot water extract & ultra-fine powder on the behavior of the memory deficit mice induced by scopolamine were investigated. Results : 1. The DDTCMT hot water extract significantly decreased the production of mIL-6, mNOS-II, mTNF-${\alpha}$, and increased the production of mIL-10, mIL-1 receptor antagonist. 2. The DDTCMT hot water extract significantly suppressed the production of IL-$1{\beta}$, IL-6, TNF-${\alpha}$ in BV2 microglial cell line treated by LPS. 3. The DDTCMT hot water extract significantly suppressed the NO and ROS production in BV2 microglial cell line treated by LPS. 4. The DDTCMT hot water extract groups showed inhibition of AChE activity in NGF treated PC-12 cell line. 5. The DDTCMT hot water extract suppressed anti-AChE expression in NGF treated PC-12 cell line was observed by Western blot analysis. 6. The DDTCMT hot water extract & ultra-fine powder groups showed significantly inhibitory effect on the scopolamine -induced impairment of memory in the experiment of Morris water maze. Conclusions : These results suggest that the DDTCMT hot water extract & ultra-fine powder may be effective for the prevention and treatment of Alzheimer's disease.

• Toxicological Research
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• v.17
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• pp.47-57
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• 2001

Alzheimer's disease (AD) is the most common cause of dementia in the elderly, and its pathology is characterized by the presence of numerous numbers of senile plaques and neurofibrillary tangles. Several genetic and transgenic studies have indicated that excess amount of $\beta$-amyloid protein (A$\beta$) is produced by mutations of $\beta$TEX>$\beta$-amyloid precursor protein and causes learning impairment. Moreover, $A\beta$ has a toxic effect on cultured nerve cells. To prepare AD model animals, we have examined continuous (2 weeks) infusion of $A\beta$ into the cerebral ventricle of rats. Continuous infusion of $A\beta$ induces learning impairment in water maze and passive avoidance tasks, and decreases choline acetyltransferase activity in the frontal cortex and hippocampus. Immunohistochemical analysis revealed diffuse depositions of $A\beta$ in the cerebral cortex and hippocampus around the ventricle. Furthermore, the nicotine-evoked release of acetylcholine and dopamine in the frontal cortex/hippocampus and striatum, respectively, is decreased in the $A\beta$-infused group. Perfusion of nicotine (50 $\mu\textrm{M}$) reduced the amplitude of electrically evoked population spikes in the CA1 pyramidal cells of the control group, but not in those of the $A\beta$-infused group, suggesting the impairment of nicotinic signaling in the $A\beta$-infused group. In fact, Kd, but not Bmax, values for ［$^3H$］ cytisine binding in the hippocampus significantly increased in the $A\beta$-infused rats. suggesting the decrease in affinity of nicotinic acetylcholine receptors. Long-term potentiation (LTP) induced by tetanic stimulations in CA1 pyramidal cells, which is thought to be an essential mechanism underlying learning and memory, was readily observed in the control group, whereas it was impaired in the $A\beta$-infused group. Taken together, these results suggest that $A\beta$ infusion impairs the signal transduction mechanisms via nicotinic acetylcholine receptors. This dysfunction may be responsible, at least in part, for the impairment of LTP induction and may lead to learning and memory impairment. We also found the reduction of glutathione- and Mn-superoxide dismutase-like immunoreactivity in the brains of $A\beta$-infused rats. Administration of antioxidants or nootropics alleviated learning and memory impairment induced by $A\beta$ infusion. We believe that investigation of currently available transgenic and non-transgenic animal models for AD will help to clarify the pathogenic mechanisms and allow assessment of new therapeutic strategies.

• Korean Journal of Human Ecology
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• v.17 no.4
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• pp.661-677
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• 2008

The purpose of this study is to develop the playground environment model for child care center by analyzing user needs of playground environment. To systemize the playground environment design factors and guidelines, we reviewed the previous research, actual measurement and observation were used as the research methodology. And to recognize the needs of users, the survey and picture survey was conducted to the staffs and children. The scope of survey included child care centers in Seoul and Daejeon, ultimately selecting 12 places in Seoul and 13 places in Daejeon. In terms of the survey period, actual measurement was conducted from June of 2006 to February of 2007, survey and picture survey was conducted from August to September of 2006. For analysis, we used SPSS 10.0 to check the frequency and percentage, as well as to perform cluster analysis. The findings of research can be summarized as below: 1. In playground environment, we observed the area of play ground and ground cover, the independence of play area, play equipment, and the composition of play area. The result of observation showed that while playground area varied widely, ground cover, play equipment, and the composition of play area turned out to be identical, regardless of the playground's area. Therefore, in order to classify various playground environments, we categorized them into 5 types, using the number of children and the area of play ground as a category. Type A had large facilities and small playground area. Type B had small sized facilities and large playground area. Type C had medium sized facilities and small playground area. Type D had medium sized facilities but large playground area. Type E had large sized facilities and large playground area. 2. On the other hand, staffs wanted a tunnel, playhouse, comprehensive play equipment, and a maze to be installed as play facilities, and there were requests for adventure play area and carpenter play area. The picture survey to children showed that they wanted equipments that can provide more thrill, adventure and challenge to them than the ones they see now. Therefore, existing child care center play environments must change from the monotonous and identical environments to the ones that can provide diversities, challenges, and adventures. In the contexts of 5 playground types suggested by this research, type B and D, E where the area of playground were larger than the legally required, should include various play areas and install appropriate play equipments and facilities. Type A and C where the area were small, should provide multipurpose play area to attract the various play behaviors of children.