• 대한한의학방제학회지
• /
• 제13권1호
• /
• pp.103-121
• /
• 2005

Alzheimer's disease(AD) is a geriatric dementia that is widespread in old age. In the near future AD will be the biggest problem in public health service. It has been widely believed that $A{\beta}$ peptide devided from APP causes apoptotic neurotoxicity in AD brain. However, recent evidence suggests that n99 may be an important factor causing neurotoxicity in AD. Mouse Neuro 2A cells expressed with CT99 exhibited remarkable apoptotic cell damage. We invesgated the protective effects of Ikgiansintang water extract(IGA). Findings from our experiment have shown that IGA inhibits the activities of CT99, which has neurotoxicities and apoptotic activities in cell line. In addition treatment of IGA($50{\mu}g/ml$ for 24 hours) partially prevented CT99-induced cytotoxicity in Neuro 2A cells. As the result of this study, In IGA group, the apoptosis in the nervous system is inhibited, the repair against the degerneration of Neuro 2A cells by n99 expression is promoted. Base on these findings, IGA may be beneficial for the treatment of AD.

• 대한한방내과학회지
• /
• 제29권3호
• /
• pp.608-620
• /
• 2008

Objectives : This study investigated the protective effects of the water extracts of Chongmyung-tang, Polygalae Radix, and Acori Graminei Rhizoma in an in vivo Alzheimer's disease (AD) mouse model. Methods : Memory impairment was induced by an intraventricular injection of $A{\beta}25-35$ peptides and subsequently Chongmyung-tang, Polygalae Radix, or Acori Graminei Rhizoma extract were administered orally for 14days. Results : In the water maze task, Chongmyung-tang, Polygalae Radix, and Acori Graminei Rhizoma extracts improved learning ability during the acquisition period and significantly increased memory scores during the retention period versus $A{\beta}-injected$ controls. Furthermore, the toxicity of $A{\beta}25-35$ on hippocampus was assessed immunohistochemically (Tau, MAP2, TUNEL, Bax) and by in vitro study. Chongmyung-tang, Polygalae Radix, and Acori Graminei Rhizoma demonstrated significant neuroprotective effects against oxidative damage and apoptotic cell death of hippocampal neurons damaged by $A{\beta}25-35$. Conclusions : These results suggested that Chongmyung-tang, Polygalae Radix and Acori Graminei Rhizoma extract improve memory impairment and reduce Alzheimer's dementia via anti-apoptotic effects and by modulating the expressions of Tau and MAP2 protein in the hippocampus.

• 동의신경정신과학회지
• /
• 제11권2호
• /
• pp.11-21
• /
• 2000

Substance P(SP) can stimulate production of tumor necrosis factor-${\alpha}$(TNF-${\alpha}$) from astrocytes stimulated with lipopolysaccharide(LPS). The objective of the current study was to determine the effect of Taraxacum officinale(TO) on the production of TNF-${\alpha}$ from primary cultures of rat astrocytes. TO(100& 1000$\mu\textrm{g}$/ml) significantly inhibited the TNF-${\alpha}$ production by astrocytes stimulated with LPS and SP. Interleukin-1(IL-1) has been shown to elevate TNF-${\alpha}$ production from LPS-stimulated astrocytes while having no effect on astrocytes in the absence of LPS. We therefore examined whether IL-1 mediated inhibition of TNF-${\alpha}$ production from primary astrocytes by TO. Treatment of TO(100 and 1000$\mu\textrm{g}$/ml) to astrocytes stimulated with both LPS and substance P decreased IL-1 production significantly. Moreover, the production of TNF-${\alpha}$ by LPS and substance P in astrocytes was progressively inhibited with increasing amount of IL-1 neutralizing antibody. These results suggest that TO may inhibit TNF-${\alpha}$ production by inhibiting IL-1 production and that TO has an antiinflammatory activity in the central nervous system.

• Journal of Korean Neurosurgical Society
• /
• 제60권2호
• /
• pp.130-137
• /
• 2017

Objective : Autophagy is one of the key responses of cells to programmed cell death. Memantine, an approved anti-dementia drug, has an antiproliferative effect on cancer cells but the mechanism is poorly understood. The aim of the present study was to test the possibility of induction of autophagic cell death by memantine in glioma cell lines. Methods : Glioma cell lines (T-98 G and U-251 MG) were used for this study. Results : The antiproliferative effect of memantine was shown on T-98 G cells, which expressed N-methyl-D-aspartate 1 receptor (NMDAR1). Memantine increased the autophagic-related proteins as the conversion ratio of light chain protein 3-II (LC3-II)-/LC3-I and the expression of beclin-1. Memantine also increased formation of autophagic vacuoles observed under a transmission electron microscope. Transfection of small interfering RNA (siRNA) to knock down NMDAR1 in the glioma cells induced resistance to memantine and decreased the LC3-II/LC3-I ratio in T-98 G cells. Conclusion : Our study demonstrates that in glioma cells, memantine inhibits proliferation and induces autophagy mediated by NMDAR1.

• Journal of Acupuncture Research
• /
• 제33권3호
• /
• pp.101-116
• /
• 2016

Objectives : This research was performed to investigate the effects of Ukgansan pharmacopuncture(U-PA) of focal brain ischemia induced by middle cerebral artery occlusion(MCAO) in rats. Methods : The subjects were divided into 5 groups : A control group, acupuncture group, pharmacopuncture group U-PA1($2.571mg/250g/40{\mu}{\ell}$), pharmacopuncture group U-PA2($6.428mg/250g/40{\mu}{\ell}$), and pharmacopuncture group U-PA3($12.855mg/250g/40{\mu}{\ell}$). The focal brain ischemia was induced by intraluminal filament insertion into the middle cerebral artery. After 3 days of MCAO, Ukgansan(UGS) pharmacopuncture treatment was performed on the GB20, and the day after being treated with pharmacopuncture, the Morris water maze test was carried out by the assigned group. The series of processes were treated 6 times. Thereafter Bax, Bcl-2, Bax/Bcl-2 ratio, mGluR5, density of neuronal cell, and ChAT were measured. Results : The results were as follows. 1. The intensity of Bax significantly decreased in the U-PA1, U-PA2, U-PA3 groups. 2. The Bax/Bcl-2 ratio significantly decreased in the U-PA3 group compared with the control group. 3. The neuroprotective effect on the hippocampal CA1 significantly increased in the U-PA1, U-PA2, U-PA3 groups compared with the control group. 4. The density of ChAT in the hippocampal CA1 significantly increased in the U-PA1, U-PA2, U-PA3 groups compared with the control group. Conclusion : These results suggest that UGS pharmacopuncture may have anti-apoptotic and neuroprotective effects on focal cerebral ischemia caused by intraluminal filament insertion into the middle cerebral artery in rats.

• 동의신경정신과학회지
• /
• 제20권2호
• /
• pp.121-131
• /
• 2009

Objectives : From Scrophularia buergeriana water extract(SBW), has been used in vivo test for its beneficial effects on neuronal survival and neuroprotective functions, particularly in connection with APP-related dementias and Alzheimer's disease(AD). $A{\beta}$ oligomer derived from proteolytic processing of the ${\beta}$-amyloid precursor protein(APP), including the amyloid-${\beta}$ peptide($A{\beta}$), play a critical role in the pathogenesis of Alzheimer's dementia. Methods : Using drosophila APP model on APP-induced neuronal cytotoxicity, we demonstrated that SBW prevents neurotoxicity of $A{\beta}$ oligomer, which are the behavior, and possibly causative, feature of AD. We investigated the neuroprotective effects of SBW against the effects of oligomeric $A{\beta}$ and fly behaveior and life span by UAS-GRIM/APP-GAL within transgenic flies. Results and Conclusions : SBW repaired damage leading to the behaveior of APP-induced fly and delayed life span. These results suggest that neuronal damage in AD might be due to two factors: a direct $A{\beta}$ oligomer toxicity and multiple cellular and molecular neuroprotective mechanisms, including attenuation of apoptosis and direct inhibition of $A{\beta}$ oligomer, underlie the neuroprotective effects of SBW.

• 보건행정학회지
• /
• 제10권4호
• /
• pp.99-115
• /
• 2000

This study was conducted to get a resonable set of budget allocation to public health programs. Matrix Delphi technique was used to obtain the logic of study results and eventually to form a human model which could predict opinion of professionals on budget allocation. Thirty-two professionals in academic and governmental area responded to Delphi survey. Questionnaire was developed using matrix formation, and the matrix was formed by 6 decision criteria on budget allocation and 26 public health programs. The decision criteria are as following: size of problem(morbidity), severity of problem, social equity, importance of prevention, technical feasibility and efficiency of programs. Severity of problem dropped out of the model because it had significant correlation with the size of problem. A total score of each program was obtained by weighting the relative importance of each criteria which also were given by survey respondents. These total scores indicate that the most important public health program is vaccination for infants and children in terms of budget allocation. Monitoring communicable diseases, mental health program, and anti-smoking program are the next. In addition, respondents were asked of the desirable budget size of each program. The result was rearranged by multiple regression model using the scores of each decision criteria. In this process, the current budget size of central government was provided to the respondents, and included in the model. h set of desirable budgets modified using tile model was obtained. Considering the current size of budget, tile results of the model is very different from that of the total score. Managing dementia is ranked the first. Health promotion program for the elderly, rehabilitation of the disabled and monitoring communicable diseases are the next. The need to increase the budget of vaccination for the infants and children was not found as so high. The matrix structure in Delphi survey gave us the precise basis to make optimal decision, and made it possible to develop an opinion predicting model. However the plentifulness and diversity of professional opinions were not fully obtained due to the limited number of decision criteria.

• 자연과학논문집
• /
• 제19권1호
• /
• pp.45-55
• /
• 2008

아세틸콜린에스터라아제(AChE)저해제에 의한 아세틸콜린 분해의 억제는 알츠하이머 질병의 환자들을 위한 치료 방법 중의 하나이다. 새로운 AChE 저해제를 개발하여 항 치매성 대체 의약품생산에 응용하기 위해, 전보에서는 다양한 곡류와 두류로부터 AChE 저해활성이 우수한 시료로 수수를 선발하여 추출 최적조건을 조사하였고 영양성 및 생리기능성 등을 조사하였다. 본 연구에서는 AChE 저해제를 함유한 수수 메탄올 추출물의 물리화학적 성질과 안정성을 조사하였다. 수수 메탄올추출물은 물, 메탄올과 DMSO등에 잘 녹았고, 215nm과 282nm의 최대흡수파장을 갖고 있었다. 또한, 추출물은 20-$100^{\circ}C$와 pH 2.0-10.0에서 1시간동안 안정 하였다. 수수 메탄올추출물을 이용하여 시제품을 제조한 후 $20^{\circ}C$와 $40^{\circ}C$에서 8주간 저장하였을 때 모두 생균수와 pH에 변화가 없이 안정하였고 기호도도 우수하게 유지되었다.

• 생명과학회지
• /
• 제17권1호
• /
• pp.150-161
• /
• 2007

Acori graminei Rhizomn (AGR) is a perennial herb which has been used clinically as a traditional oriental medicine against stroke, Alzheimer's disease, and vascular dementia. We investigated the effect of AGR on the modulation of gene expression profile in a hypoxic model of cultured rat cortical cells. Rat cerebrocortical cells were grown in Neurobasal medium. On DIV12, cells were treated with AGR $(10ug/m\ell)$, given a hypoxic shock (2% $O_2$, 3 hr) on DIV14, and total RNAs were prepared one day after shock. Microarray analyses indicated that the expression levels of most genes were altered within the global M values +0.5 and -0.5, i.e., 40% increase or decrease. There were 750 genes which were upregulated by < global M +0,2, while 700 genes were downregulated by > global M -0.2. The overall profile of gene expression suggests that AGR suppresses apoptosis (upregulation of anti-apopotic genes such as TEGT, TIEG, Dad, p53, and downregulation of pro-apopotic genes such as DAPK, caspase 2, pdcd8), ROS (upregulation of RARa, AhR), and that AGR has neurotrophic effects (upregulation of Aktl, Akt2). These results provide a platform for investigation of the molecular mechanism of the effect of AGR in neuroprotection.

• Archives of Pharmacal Research
• /
• 제28권7호
• /
• pp.799-803
• /
• 2005

In the course of screening anti-dementia agents from natural products, two $\beta$-secretase (BACE1) inhibitors were isolated from the ethyl acetate soluble fraction of Sanguisorbae Radix by the activity-guided purification using silica gel, Sephadex LH-20, and RP-HPLC. They were identified as 1,2,3-trigalloyl-4,6-hexahydroxydiphenoyl-$\beta$-D-glucopyranoside (Tellimagrandin II, 1) and 1,2,3,4,6-pentagalloyl-$\beta$-D-glucopyranoside (2) and were shown to non-competitively inhibit $\beta$-secretase (BACE1) with the $IC_{50}$ values of $3.10{\times}10^{-6}M\;and\;3.76{\times}10^{-6}M$, respectively. The Ki values of 1 and 2 were $6.84{\times}10^{-6}M\;and\;5.13{\times}10^{-6}M$. They were less inhibitory to asecretase (TACE) and other serine proteases such as chymotrypsin, trypsin, and elastase, suggesting that they were relatively specific inhibitors of BACE1.