• Journal of Oriental Neuropsychiatry
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• v.21 no.1
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• pp.109-124
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• 2010

Objectives: This experiment was designed to investigate the effect of the InSamYangYoung-tang(Renshenyangrongtang) extract on $A{\beta}$-induced AD model. Methods: The effects of the InSamYangYoung-tang(Renshenyangrongtang) extract on neural damages of cultured PC12 cells induced by $A{\beta}$ were investigated. The effects of the InSamYangYoung-tang(Renshenyangrongtang) extract on neural damages of hippocampal and cortical neurons in the mouse induced by $\beta$-amyloid were investigated. Results: 1. $A{\beta}$ treatment into neuronal cells activated cell death pathway when analyzed by MTT assay and by histological analysis. Then InSamYangYoung-tang(Renshenyangrongtang) treatment improved cell survival to a similar level as in normal group. 2. $A{\beta}$ treatment increased caspase 3 protein levels but decreased phospho-Erk1/2 in neuronal cells. InSamYangYoung-tang(Renshenyangrongtang) treatment reversed the production levels of two proteins close to those in normal group. 3. $A{\beta}$ treatment induced the atrophy of neuronal cells in terms of neuronal processes and cell body shrinkage, but InSamYangYoung-tang(Renshenyangrongtang) greatly improved their morphology. 4. Neuroprotective activity, as observed in InSamYangYoung-tang(Renshenyangrongtang)-treated groups, was similarly observed in cells treated with galantamine which was used as a positive control. Moreover, overall recovery pattern by InSamYangYoung-tang(Renshenyangrongtang) was similar between cultured PC12 cells and in vivo hippocampal and cerebral cortical neurons in the mouse brain. Conclusions: This experiment shows that the InSamYangYoung-tang(Renshenyangrongtang) may play a protective role in neural tissues damaged by cytotoxic substances. Since neuronal damage seen in degenerative brains such as AD are largely unknown, the current data may provide possible insight into therapeutic strategies for AD treatments. InSamYangYoung-tang(Renshenyangrongtang) might be effective for the treatment of AD. Investigation into the clinical use of the InSamYangYoung-tang(Renshenyangrongtang) for AD is suggested for future research.

• Journal of Ginseng Research
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• v.42 no.4
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• pp.401-411
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• 2018

Longevity in medicine can be defined as a long life without mental or physical deficits. This can be prevented by Alzheimer's disease (AD). Current conventional AD treatments only alleviate the symptoms without reversing AD progression. Recent studies demonstrated that Panax ginseng extract improves AD symptoms in patients with AD, and the two main components of ginseng might contribute to AD amelioration. Ginsenosides show various AD-related neuroprotective effects. Gintonin is a newly identified ginseng constituent that contains lysophosphatidic acids and attenuates AD-related brain neuropathies. Ginsenosides decrease amyloid ${\beta}$-protein ($A{\beta}$) formation by inhibiting ${\beta}$- and ${\gamma}$-secretase activity or by activating the nonamyloidogenic pathway, inhibit acetylcholinesterase activity and $A{\beta}$-induced neurotoxicity, and decrease $A{\beta}$-induced production of reactive oxygen species and neuro-inflammatory reactions. Oral administration of ginsenosides increases the expression levels of enzymes involved in acetylcholine synthesis in the brain and alleviates $A{\beta}$-induced cholinergic deficits in AD models. Similarly, gintonin inhibits $A{\beta}$-induced neurotoxicity and activates the nonamyloidogenic pathway to reduce $A{\beta}$ formation and to increase acetylcholine and choline acetyltransferase expression in the brain through lysophosphatidic acid receptors. Oral administration of gintonin attenuates brain amyloid plaque deposits, boosting hippocampal cholinergic systems and neurogenesis, thereby ameliorating learning and memory impairments. It also improves cognitive functions in patients with AD. Ginsenosides and gintonin attenuate AD-related neuropathology through multiple routes. This review focuses research demonstrating that ginseng constituents could be a candidate as an adjuvant for AD treatment. However, clinical investigations including efficacy and tolerability analyses may be necessary for the clinical acceptance of ginseng components in combination with conventional AD drugs.

• Journal of the Korea Society of Computer and Information
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• v.25 no.6
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• pp.165-170
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• 2020

In this paper, it was confirmed that scopoletin inhibits neuroinflammation induced by amyloid beta oligomer (Aβ_1-42) in microglial BV-2. The mechanisms of inflammatory cytokines and inflammatory mediators by scopoletin were identified. Alzheimer's disease is the most common neurodegenerative disease, but it is a disease whose specific etiology is unknown, and many studies are trying to solve it. We first measured the cell viability with the CCK-8 assay method to confirm that scopoletin and Aβ_1-42 are toxic to BV-2 cells. Expression levels of interleukin 1 beta (IL-1β), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and nuclear factor-κB (NF-κB) in inflammatory reactions induced by Aβ_1-42 with western blot were analyzed. The ANOVA assay was used to compare protein expression differences between BV-2 cells treated with Aβ_1-42 alone and BV-2 cells pretreated with Aβ_1-42 and scopoletin. Therefore, this study suggested that scopoletin is worth developing as a neuroinflammatory protection agent for Alzheimer's disease in the future.

• The Journal of Bigdata
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• v.6 no.1
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• pp.37-49
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• 2021

The number of dementia patients in Korea is estimated to be over 800,000, and the severity of dementia is becoming a social problem. However, no treatment or drug has yet been developed to cure dementia worldwide. The number of dementia patients is expected to increase further due to the rapid aging of the population. Currently, early detection of dementia and delaying the course of dementia symptoms is the best alternative. This study presented a methodology for early diagnosis of dementia by measuring and analyzing amyloid plaques. This vital protein can most clearly and early diagnose dementia in the retina through AI-based image analysis. We performed binary classification and multi-classification learning based on CNN on retina data. We also developed a deep learning algorithm that can diagnose dementia early based on pre-processed retinal data. Accuracy and recall of the deep learning model were verified, and as a result of the verification, and derived results that satisfy both recall and accuracy. In the future, we plan to continue the study based on clinical data of actual dementia patients, and the results of this study are expected to solve the dementia problem.

• 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 Microbiology and Biotechnology
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• v.32 no.9
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• pp.1154-1167
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• 2022

In this study, we investigated the anti-amnesic effect of Korean red pine (Pinus densiflora) bark extract (KRPBE) against amyloid beta_1-42 (Aβ_1-42)-induced neurotoxicity. We found that treatment with KRPBE improved the behavioral function in Aβ-induced mice, and also boosted the antioxidant system in mice by decreasing malondialdehyde (MDA) content, increasing superoxide dismutase (SOD) activities, and reducing glutathione (GSH) levels. In addition, KRPBE improved the cholinergic system by suppressing reduced acetylcholine (ACh) content while also activating acetylcholinesterase (AChE), regulating the expression of choline acetyltransferase (ChAT), postsynaptic density protein-95 (PSD-95), and synaptophysin. KRPBE also showed an ameliorating effect on cerebral mitochondrial deficit by regulating reactive oxygen species (ROS), mitochondrial membrane potential (MMP) and ATP levels. Moreover, KRPBE modulated the expression levels of neurotoxicity indicators Aβ and phosphorylated tau (p-tau) and inflammatory cytokines TNF-α, p-IκB-α, and IL-1β. Furthermore, we found that KRPBE improved the expression levels of neuronal apoptosis-related markers BAX and BCl-2 and increased the expression levels of BDNF and p-CREB. Therefore, this study suggests that KRPBE treatment has an anti-amnestic effect by modulating cholinergic system dysfunction and neuroinflammation in Aβ_1-42-induced cognitive impairment in mice.

• The Korean Journal of Food And Nutrition
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• v.19 no.1
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• pp.62-69
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• 2006

This study was performed to investigate the biocogical activity of the phospholipid separated and purified from duck egg yolk as functional brain food. A quantitative restriction of maternal diet was given to Sprague-Dawely rats during lactation. Animals were separated into three groups, such as control, duck egg phospholipid(PL) or pig-brain phospholipid additions groups. And ad libitum during lactation was given to control groups. All of the offsprings at 3 weeks of age fed a diet ad libitum for 4 weeks of rehabilitation. Body weight and brain weight and protein, phosphplipid, and cholesterol were determined on offsprings of each of group sacrificed at 0, 1, 2, 3, 5 and 7 weeks of age, sacrified body weight of duck egg phospholipid and pig brain phospholipid group were significantly higher than the control group. Body weight and brain weight after a recovery period were significantly at the control group. However, protein, phospholipid and cholesterol contents were significantly high than the control group. Response latency in the passive avoidance task was the lowest in the ${\beta}$-amyloid group and highest in the phospholipid group. It is consequently suggested that phospholipid supplement may be effective in memory improvement.

• 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 Life Science
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• v.26 no.7
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• pp.868-874
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• 2016

Receptor-interacting protein kinase 1 (RIPK1) and RIPK3 are members of the serine or threonine protein kinase superfamily that phosphorylates the hydroxyl group of serine or threonine through the highly conserved kinase region. The RIPK family plays a crucial role not only in inflammation and innate immunity, but also in mediating programmed cell death, such as apoptosis and necroptosis. The interaction between RIPK1 and other TNFR1-related proteins has been shown to assemble a signaling complex I that controls activation of the pro-survival transcription factor NF-κB upon binding of cytokines to TNF receptor 1 (TNFR1). Moreover, RIPK1 and RIPK3 interact through their RIP homotypic interaction motifs (RHIMs) to mediate programmed necrosis, which has long been considered an accidental and uncontrolled cell death form with morphological characteristics differing from those of apoptosis. Highly conserved sequences of RHIM in RIPK1 and RIPK3 were shown to regulate their binary interaction, leading to assembly of a cytosolic amyloid complex termed the “necrosome”. The necrosome also contains mixed lineage kinase domain-like protein (MLKL), which has been found recently to be a substrate of RIPK3 to mediate downstream signaling. This review provides an overview of the functional and physiological characteristics of RIPKs and MLKL in TNF signaling.

• 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.