• Journal of Ginseng Research
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• v.45 no.6
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• pp.665-675
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• 2021

Background: Ginsenoside Rg1 (Rg1), an active ingredient in ginseng, may be a potential agent for the treatment of Alzheimer's disease (AD). However, the protective effect of Rg1 on neurodegeneration in AD and its mechanism of action are still incompletely understood. Methods: Wild type (WT) and APP/PS1 AD mice, from 6 to 9 months old, were used in the experiment. The open field test (OFT) and Morris water maze (MWM) were used to detect behavioral changes. Neuronal damage was assessed by hematoxylin and eosin (H&E) and Nissl staining. Immunofluorescence, western blotting, and quantitative real-time polymerase chain reaction (q-PCR) were used to examine postsynaptic density 95 (PSD95) expression, amyloid beta (Aβ) deposition, Tau and phosphorylated Tau (p-Tau) expression, reactive oxygen species (ROS) production, and NAPDH oxidase 2 (NOX2) expression. Results: Rg1 treatment for 12 weeks significantly ameliorated cognitive impairments and neuronal damage and decreased the p-Tau level, amyloid precursor protein (APP) expression, and Aβ generation in APP/PS1 mice. Meanwhile, Rg1 treatment significantly decreased the ROS level and NOX2 expression in the hippocampus and cortex of APP/PS1 mice. Conclusions: Rg1 alleviates cognitive impairments, neuronal damage, and reduce Aβ deposition by inhibiting NOX2 activation in APP/PS1 mice.

• Journal of Oriental Neuropsychiatry
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• v.16 no.1
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• pp.97-117
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• 2005

This research investigates the effect of the Chaenomelis fructus(CMF) on Alzheimer's disease. Specifically, the effects of the CMF extract on (1) >$IL-1{\beta}$, IL-6, and $TNF-{\alpha}$ mRNA of PC-12 cells treated with LPS; (2) amyloid precursor proteins(APP), acetylcholinesterase(AChE), and glial fibrillary acidic protein(GFAP) mRNA of PC-12 cells treated with CT-105; (3) the AChE activity and the APP production of PC-12 cell treated with CT-105; (4) the behavior of AD mice with ${\beta}A$; (5) expression of $IL-1{\beta}$, $TNF-{\alpha}$, MDA, $IL-1{\beta}$ mRNA, $TNF-{\alpha}$ mRNA, and ROS; (6) the infarction area of the hippocampus, and brain tissue injury in Alzheimer's diseased mice induced with ${\beta}A$ were investigated. The results were summarized as follows; 1. The CMF extract suppressed the expression of $IL-1{\beta}$, IL-6 and $TNF-{\alpha}$ mRNA in THP-1 cells treated with LPS. 2. The CMF extract suppressed the expression of APP, AChE, and GFAP mRNA in PC-12 cells treated with CT-105. 3. The CMF extract suppressed the AChE activity, and the production of APP significantly in PC-12 cells treated with CT-105. 4. A significant inhibitory effect on the memory deficit was shown on the CMF extract group of 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. 5. The CMF extract suppressed the over-expression of $IL-1{\beta}$ protein, $TNF-{\alpha}$ protein, MDA, $IL-1{\beta}$ protein, mRNA, $TNF-{\alpha}$ mRNA, CD68/GFAP, and ROS in the mice with Alzheimer's disease induced by ${\beta}A$. 6. The CMF extract reduced the infarction area of hippocampus, and controlled the injury of brain tissue in the mice with Alzheimer’s disease induced by ${\beta}A$. These results suggest that the CMF extract may be effective for the treatment of Alzheimer’s disease. Investigation into the clinical use of the CMF extract for Alzheimer's disease is suggested for future research.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.1
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• pp.130-138
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• 2005

This experiment was designed to investigate the effect of Phellodendron amurense(PLDA) on the Alzheimer's disease. The effects of PLDA extract on $IL-1{\beta}$, IL-6, amyloid precursor proteins(APP), acetylcholinesterase(AChE), glial fibrillary acidic protein(GFAP) mRNA of PC-12 cell treated by $A{\beta}$ plus $rIL-1{\beta}$ and AChE activity of PC-12 cell lysate treated by $A{\beta}$ plus $rIL-1{\beta}$ and behavior of memory deficit mice induced by scopolamine and mice glucose, uric acid, AChE activity of memory deficit rats induced by scopolamine were investigated, respectively. PLDA extract suppressed $IL-1{\beta}$, IL-6, APP, AChE, GFAP mRNA in PC-12 cell treated by $A{\beta}$ plus $rIL-1{\beta}$ ; AChE activity in cell lysate of PC-12 cell treated by $A{\beta}$ plus $rIL-1{\beta}$. PLDA extract increased glucose, decreased uric acid and AChE significantly in the serum of the memory deficit rats induced by scopolamine. PLDA extract group showed significantly inhibitory effect on the memory deficit of mice induced by scopolamine in the experiment of Morris water maze. According to the above results, it is suggested that PLDA extract might be usefully applied for prevention and treatment of Alzheimer's disease.

• Journal of Oriental Neuropsychiatry
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• v.13 no.2
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• pp.173-194
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• 2002

Alzheimer's disease(AD) is a geriatric dementia that is widespread in old age. In the future AD will be the largest problem in public health service. From old times, Much medicines have been used for treatment of dementia, but there is no medicine having obvious effect. AD is one of brain retrogression disease. So We studied on herbal medicine that have a relation of brain retrogression. From old times, In Oriental Medicine, Rhizoma Acori Graminei has been used for disease in relation to brain retrogression. We studied on the effects of anti-Alzheimer in pCT105-induced neuroblastoma cell lines by Rhizoma Acori Graminei extract As the result of this study, In RAG group, the apoptosis in the nervous system is inhibited, the repair against the degerneration of Neuroblastoma cells by CT105 expression is promoted. These results indicate that RAG possess strong inhibitory effect of apoptosis in the nervous system and repair effect against the degeneration of Neuroblastoma cells by CT105 expression.

• Journal of Oriental Neuropsychiatry
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• v.15 no.1
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• pp.87-99
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• 2004

This experiment was designed to investigate the effect of Coptis japonica Makino(CJM) on the Alzheimer's disease. The effects of CJM extract on $IL-1{\beta}$, IL-6, amyloid precursor proteins (APP), acetylcholinesterase(AChE), glial fibrillary acidic protein(GFAP) mRNA of PC-12 cell treated by $A{\beta}$ plus $rIL-1{\beta}$ and AChE activity of PC-12 cell lysate treated by $A{\beta}$ plus $rIL-1{\beta}$ and behavior of memory deficit rats induced by scopolamine and mice glucose, uric acid, AChE activity of memory deficit rats induced by scopolamine were investigated, respectively. The results were summarized as follows ; 1. CJM extract suppressed $IL-1{\beta}$, IL-6 mRNA in PC-12 cell treated by $A{\beta}$ plus $rIL-1{\beta}$ 2. CJM extract suppressed APP, AChE, GFAP mRNA in PC-12 cell treated by $A{\beta}$ plus $rIL-1{\beta}$ 3. CJM extract suppressed AChE activity in cell lysate of PC-12 cell treated by $A{\beta}$ plus $rIL-1{\beta}$ 4. CJM extract group showed significantly inhibitory effect on the memory deficit of mice induced by scopolamine in the experiment of Morris water maze. 5. CJM extract increased glucose, decreased uric acid and AChE significantly in the serum of the memory deficit rats induced by scopolamine. According to the above results, it is suggested that CJM extract might be usefully applied for prevention and treatment of Alzheimer's disease and memory deficit symptom.

• Proceedings of the Korean Biophysical Society Conference
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• 2003.06a
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• pp.47-47
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• 2003

The presenilin 1 (PS1) or PS2 is an essential component of the ${\gamma}$-secretase complex, which mediates the intramembrane proteolysis of selected type-I membrane, including the ${\beta}$-amyloid precursor protein (APP) to yield A${\beta}$. Familial Alzheimer's disease (FAD)-associated mutations in presenilins give rise to an increased production of a highly amyloidogenic A${\beta}$42. In addition to their well-documented proteolytic function, the presenilins play a role in calcium signaling. We have previously reported that presenilin FAD mutations cause highly consistent alterations in intracellular calcium signaling pathways, which include deficits in capacitative calcium entry (CCE), the refilling mechanism for depleted internal calcium stores. However, molecular basis for the presenilin-mediated modulation of CCE remains to be elucidated. In the present study, whole-cell patch clamp method was used to identify a specific calcium-permeable ion channel current(s) that is responsible for the CCE deficits associated with FAD-linked PS1 mutants. Unexpectedly, both voltage-activated and conventional store depletion-activated calcium currents I(CRAC), were absent in HEK293 cells, which were stably transfected either with wild-type or FAD mutant (L286V, M146L, and delta E9) forms of PS1. Recently, magnesium-nucleotide-regulated metal cation current, or I(MagNum), has been described and appears to share many common properties with I(CRAC) including calcium permeability and inhibitor sensitivity (e.g. 2-APB). We have detected I(MagNum) in all 293 cells tested. Interestingly, FAD mutant 293 cells developed only about half of currents compared to PS1 wild type cells.

• Journal of Oriental Neuropsychiatry
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• v.16 no.1
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• pp.81-96
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• 2005

This experiment was designed to investigate the effect of Dichroa febrifuga(DIF) on the Alzheimer’s disease. The effects of DIF extract on $IL-1{\beta}$, IL-6, $TNF-{\alpha}$ mRNA of THP-1 cell treated by $A{\beta}$ plus LPS and amyloid precursor proteins(APP), acetylcholinesterase(AChE), glial fibrillary acidic protein(GFAP) mRNA of PC-12 cell treated by $A{\beta}$ plus $rIL-1{\beta}$ and AChE activity of PC-12 cell lysate treated by $A{\beta}$ plus $rIL-1{\beta}$ and behavior of memory deficit mice induced by scopolamine and mice glucose, uric acid, AChE activity of memory deficit rats induced by scopolamine were investigated, respectively. The results were summarized as follows ; 1. DIF extract suppressed APP, AChE, GFAP mRNA in PC-12 cell treated by $A{\beta}$. 2. DIF extract suppressed $IL-1{\beta}$, IL-6, $TNF-{\alpha}$ mRNA in THP-1 cell treated by LPS. 3. DIF extract suppressed AChE activity in cell lysate of PC-12 cell treated by $A{\beta}$. 4. DIF extract increased glucose, decreased uric acid and AChE significantly in the serum of the memory deficit rats induced by scopolamine. 5. DIF extract group showed significantly inhibitory effect on the memory deficit of mice induced by scopolamine in the experiment of Morris water maze. According to the above results, it is suggested that DIF extract might be usefully applied for prevention and treatment of Alzheimer’s disease and memory deficit.

• Journal of Oriental Neuropsychiatry
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• v.16 no.1
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• pp.67-80
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• 2005

This experiment was designed to investigate the effect of Rheum palmatum(RHP) on the Alzheimer's disease. The effects of RHP extract on amyloid precursor proteins(APP), acetylcholinesterase(AChE), glial fibrillary acidic protein(GFAP) mRNA of PC-12 cell treated by $A{\beta}\;and\;IL-1{\beta},\;IL-6,\;TNF-{\alpha}$ mRNA of THP-1 cell treated by LPS and AChE activity of PC-12 cell lysate treated by $A {\beta}$and behavior of memory deficit rats induced by scopolamine and mice glucose, uric acid, AChE activity of memory deficit rats induced by scopolamine were investigated, respectively. The results were summarized as follows ; 1. RHP extract suppressed APP, AChE, GFAP mRNA in PC-12 cell treated by $A{\beta} $. 2. RHP extract suppressed $IL-1{\beta} $, IL-6 $TNF-{\alpha}$ mRNA in THP-1 cell treated by LPS. 3. RHP extract suppressed AChE activity in cell lysate of PC-12 cell treated by $A{\beta}$. 4. HP extract increased glucose, decreased uric acid and AChE significantly in the serum of the memory deficit rats induced by scopolamine. 5. RHP extract group showed significantly inhibitory effect on the memory deficit of mice induced by scopolamine in the experiment of Morris water maze. According to the above results, it is suggested that RHP extract might be usefully applied for prevention and treatment of Alzheimer’s disease and memory deficit symptom.

• Biomolecules & Therapeutics
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• v.20 no.3
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• pp.332-339
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• 2012

The components of Magnolia officinalis have well known to act anti-inflammatory, anti-oxidative and neuroprotective activities. These efficacies have been sold many products as nutritional supplement extracted from bark of Magnolia officinalis. Thus, to assess and compare neuroprotective effect in the nutritional supplement (Magnolia $Extract^{TM}$, Health Freedom Nutrition LLC, USA) and our ethanol extract of Magnolia officinalis (BioLand LTD, Korea), we investigated memorial improving and anti-Alzheimer's disease effects of extract products of Magnolia officinalis in a transgenic AD mice model. Oral pretreatment of two extract products of Magnolia officinalis (10 mg/kg/day in 0.05% ethanol) into drinking water for 3 months ameliorated memorial dysfunction and prevented $A{\beta}$ accumulation in the brain of Tg2576 mice. In addition, extract products of Magnolia officinalis also decreased expression of ${\beta}$-site APP cleaving enzyme 1 (BACE1), amyloid precursor protein (APP) and its product, C99. Although both two extract products of Magnolia officinalis could show preventive effect of memorial dysfunction and $A{\beta}$ accumulation, our ethanol extract of Magnolia officinalis (BioLand LTD, Korea) could be more effective than Magnolia $Extract^{TM}$ (Health Freedom Nutrition LLC, USA). Therefore, our results showed that extract products of Magnolia officinalis were effective for prevention and treatment of AD through memorial improving and anti-amyloidogenic effects via down-regulating ${\beta}$-secretase activity, and neuroprotective efficacy of Magnolia extracts could be differed by cultivating area and manufacturing methods.

• Journal of Life Science
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• v.20 no.7
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• pp.1012-1018
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• 2010

The aim of this study was to determine whether Alzheimer's amyloid precursor protein (APP) is dysregulated in adipose tissues of C57BL/6 male mice by high-fat diet (HFD) induced obesity, aging, or streptozotocin (STZ)-induced diabetes. APP mRNA expression was examined by quantitative real-time PCR (QPCR) in subcutaneous (SAT) and epididymal adipose tissues (EAT) from mice in 8 different condition groups. By combining conditions of age (16 weeks/26 weeks of age), diet (normal diet (ND)/high-fat diet), and induction of diabetes (non-diabetic/diabetic), 88 mice were divided into 8 different groups. QPCR demonstrated that APP expression in SAT was significantly increased by about two-fold in HFD-induced obese mice compared to both 16 week-old and 26 week-old mice in the ND group (16 weeks p=0.001; 26 weeks p<0.0001), but no changes in EAT was found. Particular effects of aging on APP gene expression were not observed in either adipose tissue depots. Significantly decreased APP expression was found in SAT in STZ-induced diabetic mice fed on ND or HFD at 16 weeks of age (ND p<0.05; HFD p<0.01). Linear regression analysis demonstrated that APP expression levels correlated with body weight in both the non-diabetic group (R=0.657, p<0.0001, n=39) and the diabetic group (R=0.508, p=<0.0001, n=49), but did not correlate with plasma glucose levels, which suggests that decreased APP expression in STZ-induced diabetic mice is most likely due to weight loss rather than hyperglycemia. These data confirm APP dysregulation by weight changes in humans and suggest a possible role linking midlife obesity with the later development of amyloidogenesis in the brain of older patients with Alzheimer's disease.