• Journal of Applied Biological Chemistry
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• v.64 no.3
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• pp.299-307
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• 2021

Accumulation of amyloid beta (Aβ) and oxidative stress are the most common reason of Alzheimer's disease (AD). In the present study, we investigated the cognitive improvement effects of butanol (BuOH) fraction from Momordica charantia in Aβ_25-35-induced AD mouse model. To develop an AD mouse model, mice were received injection of Aβ_25-35, and then orally administered BuOH fraction from M. charantia at doses of 100 and 200 mg/kg/day during 14 days. In the T-maze and novel object recognition test, administration of BuOH fraction from M. charantia L. at doses of 100 and 200 mg/kg/day improved spatial ability and novel object recognition by increased explorations of novel route and new object. In addition, BuOH fraction of M. charantia-administered groups improved learning and memory abilities by decreased time to reach hidden platform in Morris water maze test. Oral administration of BuOH fraction from M. charantia significantly inhibited lipid peroxidation and nitric oxide levels in the brain, liver, and kidney compared with Aβ_25-35-induced control group. These results indicated that BuOH fraction of M. charantia improved Aβ_25-35-induced cognitive impairment by attenuating oxidative stress. Therefore, M. charantia could be useful for protection from Aβ_25-35-induced cognitive impairment.

• Journal of Ginseng Research
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• v.45 no.2
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• pp.325-333
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• 2021

Background: Alzheimer's disease (AD) is one of the most prevalent neurodegenerative disorders. Enhancing hippocampal neurogenesis by promoting proliferation and differentiation of neural stem cells (NSCs) is a promising therapeutic strategy for AD. 20(S)-protopanaxadiol (PPD) and oleanolic acid (OA) are small, bioactive compounds found in ginseng that can promote NSC proliferation and neural differentiation in vitro. However, it is currently unknown whether PPD or OA can attenuate cognitive deficits by enhancing hippocampal neurogenesis in vivo in a transgenic APP/PS1 AD mouse model. Here, we administered PPD or OA to APP/PS1 mice and monitored the effects on cognition and hippocampal neurogenesis. Methods: We used the Morris water maze, Y maze, and open field tests to compare the cognitive capacities of treated and untreated APP/PS1 mice. We investigated hippocampal neurogenesis using Nissl staining and BrdU/NeuN double labeling. NSC proliferation was quantified by Sox2 labeling of the hippocampal dentate gyrus. We used western blotting to determine the effects of PPD and OA on Wnt/GSK3β/β-catenin pathway activation in the hippocampus. Results: Both PPD and OA significantly ameliorated the cognitive impairments observed in untreated APP/PS1 mice. Furthermore, PPD and OA significantly promoted hippocampal neurogenesis and NSC proliferation. At the mechanistic level, PPD and OA treatments resulted in Wnt/GSK-3β/β-catenin pathway activation in the hippocampus. Conclusion: PPD and OA ameliorate cognitive deficits in APP/PS1 mice by enhancing hippocampal neurogenesis, achieved by stimulating the Wnt/GSK-3β/β-catenin pathway. As such, PPD and OA are promising novel therapeutic agents for the treatment of AD and other neurodegenerative diseases.

• Journal of the Korean Society of Food Science and Nutrition
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• v.38 no.4
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• pp.409-414
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• 2009

The aim of this study was to investigate the ameliorating effects of deer antler extract on the learning and memory impairments induced by the administration of scopolamine (2 mg/kg, i.p.) in rats. Tacrine was used as a positive control agent for evaluating the cognition enhancing activity of deer antler extract in scopolamine-induced amnesia models. The results showed that the deer antler extract-treated group (200 mg/kg, p.o.) and the tacrine-treated group (10 mg/kg, p.o.) significantly ameliorated scopolamine-induced amnesia based on the Morris water maze test. Although there was no statistical significance of brain ACh contents among the experimental groups, the brain ACh contents of the deer antler extract-treated group was slightly higher than that of the scopolamine-treated group. The inhibitory effect of deer antler extract on the acetylcholinesterase activity in the brain was significantly lower than that of scopolamine-treated group. The tacrine- and the deer antler-treated groups reduced the MAO-B activity compared to the scopolamine-treated group, but not significantly. These results suggest that the deer antler extract could be an effective agent for the prevention of the cognitive impairment induced by cholinergic dysfunction.

• Korean Journal of Food Science and Technology
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• v.51 no.4
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• pp.379-392
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• 2019

The current study investigated the effect of Gabjubaekmok (Diospyros kaki) ethanolic extract (GEE) on $H_2O_2$-induced human neuroblastoma MC-IXC cells and amyloid beta $(A{\beta})_{1-42}$-induced ICR (Institute of Cancer Research) mice. GEE showed significant antioxidant activity that was evaluated based on ABTS, DPPH scavenging activity, and inhibition of malondialdehyde (MDA) and acetylcholinesterase activity. Further, GEE inhibited ROS production and increased cell viability in $H_2O_2$-induced MC-IXC cells. Administration of GEE ameliorated the cognitive dysfunction on $A{\beta}$-induced ICR mice as evaluated using Y-maze, passive avoidance, and Morris water maze tests. Results of ex vivo test using brain tissues showed that, GEE protected the cholinergic system and mitochondrial functions by increasing the levels of antioxidants such as ROS, mitochondrial membrane potential (MMP), and adenosine triphosphate (ATP) against $A{\beta}$-induced cognitive dysfunction. Moreover, GEE decreasd the expression levels of apoptosis-related proteins such as $TNF-{\alpha}$, p-JNK, p-tau, BAX and caspase 3. While, expression levels of p-Akt and $p-GSK3{\beta}$ increased than $A{\beta}$ group. Finally, gallic acid was identified as the main compound of GEE using high performance liquid chromatography.

• 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.

• 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.

• Journal of Oriental Neuropsychiatry
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• v.17 no.2
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• pp.91-122
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• 2006

Objective : This research investigates the effect of the Jangwon-Dan,(JWD) on Alzheimer's disease. Method : The effects of the JWN 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, the AChE activity and the APP production of PC-12 cell treated with CT-105; (3) the behavior; (4) expression of $IL-1{\beta}$, $TNF-{\alpha}$, MDA, $IL-1{\beta}$ mRNA, and $TNF-{\alpha}$ mRNA, (5) the infarction area of the hippocampus, and brain tissue injury in Alzheimer's diseased mice induced with ${\beta}A$ were investigated. Result : 1. The JWN extract suppressed the expression of $IL-1{\beta}$, IL-6 and $TNF-{\alpha}$ mRNA in THP-1 cells treated with LPS. 2. The JWN extract suppressed the expression of APP, AChE, and GFAP mRNA in PC-12 cells treated with CT-105. 3. The JWN extract suppressed the AChE activity, and the production of APP significantly in PC-12 cells treated with CT-105. 4. For the JWN extract group 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. 5. The JWN extract suppressed the over-expression of $IL-1{\beta}$ protein, $TNF-{\alpha}$ protein, MDA, $IL-1{\beta}$ mRNA, $TNF-{\alpha}$ mRNA, and CD68/GFAP, in the mice with Alzheimer's disease induced by ${\beta}A$. 6. The JWN extract reduced the infarction area of hippocampus, and controlled the injury of brain tissue in the mice with Alzheimer's disease induced by ${\beta}A$. Conclusion : These results suggest that the JWN extract may be effective for the prevention and treatment of Alzheimer's disease. Investigation into the clinical use of the JWN extract for Alzheimer's disease is suggested for future research.

• Journal of Oriental Neuropsychiatry
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• v.21 no.2
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• pp.171-189
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• 2010

Objectives : This research investigates the effect of the HBSBS on Alzheimer's disease. Specifically, the effects of the HBSBS extract on (1) the behavior (2) the infarction area of the hippocampus, and brain tissue injury in Alzheimer's disease mice induced with $\beta$A were investigated. Methods : The effects of the HBSBS extract suppressed the expression of IL-1$\beta$, IL-6, TNF-$\alpha$ and NOS-II mRNA in BV2 microglial cell line treated with LPS plus $\beta$A were investigated. The effects of the HBSBS extract on the behavior of the memory deficit mice induced by scopolamine were investigated. Results : 1. The HBSBS extract suppressed the expression of IL-1$\beta$, IL-6, TNF-$\alpha$ and NOS-II mRNA in BV2 microglial cell line treated with LPS plus $\beta$A. 2. The HBSBS extract suppressed the expression of $\beta$A protein production in BV2 microglial cell line treated with LPS plus $\beta$A. 3. The HBSBS extract showed significantly inhibitory effect on the scopolamine-induced impairment of memory in the experiment of Morris water maze. 4. The HBSBS group suppressed the over-expression of IL-1$\beta$ protein, TNF-$\alpha$ protein significantly in the mice with Alzheimer's disease induced by $\beta$A. 5. The HBSBS group reduced the infarction area of hippocampus, and controlled the injury of brain tissue in the mice with Alzheimer's disease induced by $\beta$A. 6. The HBSBS group reduced tau protein, and GFAP in the brain tissue of the mice with AD induced by $\beta$A. Conclusions : These results suggest that the HBSBS group may be effective for the treatment of AD. Thus, HBSBS could be considered among the future therapeutic drugs indicated for the treatment of AD.

• Journal of Life Science
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• v.30 no.8
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• pp.708-712
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• 2020

Vacuolar protein sorting (VPS) 26b is a newly discovered member of the retromer complex; it is encoded by a single-copy gene located on mouse chromosome 9, and the complex has been reported as being composed of proteins VPS26, VPS29, and VPS35. We have previously shown that mice lacking VPS26b exhibited no significant body size or health issues. Although retromer components are widely expressed in mouse tissue, their roles have not yet been completely elucidated. The current study investigates whether the VPS26b-associated retromer complex can be used as a neurodegeneration model. Previously, we observed a significant reduction in VPS35 and VPS29 in the brain cells of in VPS26b-deficient mice as well as an absence of the VPS26b-VPS29-VPS35 retromer complex despite the normal presence of VPS26a-VPS29-VPS35. Recent studies have suggested that low levels of VPS35 can lead to Alzheimer's disease-like phenotypes including cognitive memory deficits. In this study, we successfully demonstrate an association between the absence of the VPS26b-VPS29-VPS35 retromer complex, reduced cell density in the CA3 region of the hippocampus, and learning disability in VPS26b knock-out mice. The results also indicate that the VPS26b-associated retromer complex affects neurodegenerative disorders and learning processes.

• Journal of Oriental Neuropsychiatry
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• v.17 no.1
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• pp.37-57
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• 2006

Objective : This research investigates the effect of the CMT and MCMT on Alzheimer‘s disease. Methods : The effects of the CMT and MCMT extract on (1) amyloid precursor proteins(APP), acetylcholinesterase(AChE) mRNA of PC-12 cells treated with CT-105; (2) the AChE activity and the APP production of PC-12 cell treated with CT-105; (3) the behavior; (4) expression of $IL-1{\beta}$, $TNF-{\alpha}$, MDA, GFAP, CD68 abd CD11b; (5) the infarction area of the hippocampus in Alzheimer's diseased mice induced with ${\beta}A$ were investigated. Results : 1. The CMT and MCMT extract suppressed the expression of APP, AChE, and mRNA in PC-12 cells treated with CT-105. 2. The CMT and MCMT extract suppressed the AChE activity, and the production of APP significantly in PC-12 cells treated with CT-105. 3. For the CMT and MCMT extract group 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. 4. The CMT and MCMT extract suppressed the over-expression of $IL-1{\beta}$, $TNF-{\alpha}$, MDA, GFAP, CD68 abd CD11bCD68/GFAP, in the mice with Alzheimer's disease induced by ${\beta}A$. 5. The CMT and MCMT extract reduced the infarction area of hippocampus with Alzheimer's disease induced by ${\beta}A$ 6. The MCMT showed more excellent effects than CMT in the every experiments except PC-12 cells. Conclusions : These results suggest that the CMT and MCMT extract may be effective for the prevention and treatment of Alzheimer's disease. Investigation into the clinical use of the CMT and MCMT extract for Alzheimer's disease is suggested for future research.