• 사상체질의학회지
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• 제20권3호
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• pp.151-163
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• 2008

1. Objective This study was done to identify the anti-stress effect of Hyeongbangdojeok-san (HDS), Yanggyeoksanhwa-tang(YST) in Soyangin. 2. Methods Experimental animals were composed of YST, HDS+stress groups which were administered each by 200mg/kg, 400mg/kg and the Saline+stress group. On the 1st day, making the rats forced swim and on the 2nd day, applying Forced swimming test to the rats. After FST, the levels of Corticosterone in the blood were measured. For the study of learning retardation, memory ability and anxiety reaction, experimental animals were composed of YST, HDS+restraint stress groups which were administered each by 400mg/kg, no stress group and the Saline+restraint stress group. Restraint stress were applied 2 hours a day for 3 weeks. On the last day of the 3rd week, Elevated Plus Maze(EPM) was applied to the groups and Morris Water Maze(MWM) was applied to the groups for 7 days. 3. Results 1. As the results of measuring FST which reflects depression, the YST+stress group and the HDS+stress group showed significant effect in comparison with the Saline+stress group. The levels of Corticosterone in the blood were decreased only in the 400mg/kg YST+stress group. 2. As the results of measuring how long EPM which reflects anxiety reaction stayed in the open arm, there was the trend which can suppress anxiety reaction in the HDS+restraint stress group bur no statistical significance. But there was any suppression of anxiety reaction in the YST+restraint stress group. 3. According to the result of MWM, the saline+restraint stress group showed the learning retardation which means increased time arriving at goal compared to the normal group at the second and third day of measurement. On the contrary, a learning retardation was significantly decreased in the YST+restraint stress group at the third day of measurement. 4. Among the Probe trial test a memory loss occurred in the saline+restraint stress group, but memory ability was significantly increased in the YST+restraint stress group. 4. Conclusion: As the results above, Soyangin Yanggyeoksanhwa-tang has significant influence to the antidepression effect, the learning retardation, the anxiety reaction and also in the Hormone level. Hyeongbangdojeok-san has significant influence to the antidepression effect, in the Hormone level, bur not to the learning retardation and anxiety reaction. prefer to drink cold water, and who are suffering from chronic gastritis.

• Biomolecules & Therapeutics
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• 제23권6호
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• pp.571-581
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• 2015

${\beta}$-asarone (BAS) is an active component of Acori graminei rhizoma, a traditional medicine used clinically in treating dementia and chronic stress in Korea. However, the cognitive effects of BAS and its mechanism of action have remained elusive. The purpose of this study was to examine whether BAS improved spatial cognitive impairment induced in rats following chronic corticosterone (CORT) administration. CORT administration (40 mg/kg, i.p., 21 days) resulted in cognitive impairment in the avoidance conditioning test (AAT) and the Morris water maze (MWM) test that was reversed by BAS (200 mg/kg, i.p). Additionally, as assessed by immunohistochemistry and RT-PCR analysis, the administration of BAS significantly alleviated memory-associated decreases in the expression levels of brain-derived neurotrophic factor (BDNF) and cAMP-response element-binding protein (CREB) proteins and mRNAs in the hippocampus. Also, BAS administration significantly restored the expression of Bax and Bcl-2 mRNAs in the hippocampus. Thus, BAS may be an effective therapeutic for learning and memory disturbances, and its neuroprotective effect was mediated, in part, by normalizing the CORT response, resulting in regulation of BDNF and CREB functions and anti-apoptosis in rats.

• Journal of Ginseng Research
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• 제40권1호
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• pp.9-17
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• 2016

Background: Alzheimer's disease (AD) is a progressive brain disease, for which there is no effective drug therapy at present. Ginsenoside Rg1 (G-Rg1) and G-Rg2 have been reported to alleviate memory deterioration. However, the mechanism of their anti-AD effect has not yet been clearly elucidated. Methods: Ultra performance liquid chromatography tandem MS (UPLC/MS)-based metabolomics was used to identify metabolites that are differentially expressed in the brains of AD mice with or without ginsenoside treatment. The cognitive function of mice and pathological changes in the brain were also assessed using the Morris water maze (MWM) and immunohistochemistry, respectively. Results: The impaired cognitive function and increased hippocampal $A{\beta}$ deposition in AD mice were ameliorated by G-Rg1 and G-Rg2. In addition, a total of 11 potential biomarkers that are associated with the metabolism of lysophosphatidylcholines (LPCs), hypoxanthine, and sphingolipids were identified in the brains of AD mice and their levels were partly restored after treatment with G-Rg1 and G-Rg2. G-Rg1 and G-Rg2 treatment influenced the levels of hypoxanthine, dihydrosphingosine, hexadecasphinganine, LPC C 16:0, and LPC C 18:0 in AD mice. Additionally, G-Rg1 treatment also influenced the levels of phytosphingosine, LPC C 13:0, LPC C 15:0, LPC C 18:1, and LPC C 18:3 in AD mice. Conclusion: These results indicate that the improvements in cognitive function and morphological changes produced by G-Rg1 and G-Rg2 treatment are caused by regulation of related brain metabolic pathways. This will extend our understanding of the mechanisms involved in the effects of G-Rg1 and G-Rg2 on AD.

• 생명과학회지
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• 제30권8호
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• pp.708-712
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• 2020

리트로머(retromer)는 VPS26, VPS29, VPS35 분자로 구성된 복합체로, 세포막에 존재하는 특정 단백질을 엔도솜에서 트렌스골지망으로 리사이클에 관여하는 단백질 복합체이다. 2000년대 초반 콜롬비아대학의 Scott A, Small 팀에 의해서, 알츠하이머 환자에서 리트로머 분자의 발현량이 저하된다는 것을 발견하였으며, 리트로머를 구성하는 VPS35 발현을 저하시킨 마우스를 이용한 Morris Water Maze (MWM) 실험에서 인지능력이 떨어진다는 것을 보고 하였다. 본 연구진은 리트로머를 구성하는 VPS26 분자에 대한 서브타입인 VPS26b를 발견하였고, 낙아웃 마우스를 제작하였다. VPS26b 낙아웃 마우스 뇌조직을 이용한 웨스턴 블롯 결과, 낙아웃 마우스 뇌조직에서 VPS29와 VPS35의 발현량의 50% 정도로 감소되는 것을 확인하였다. 또한, VPS29 낙아웃 마우스를 이용하여 MWM실험은 한 결과 인지능력이 저하되는 것을 확인하였으며 뇌조직의 해마 CA3영역의 세포 분포도가 정상마우스에 비해 감소되는 것을 확인하였다. 결과적으로 이번 연구를 통하여 VPS26b 낙아웃 마우스는 뇌질환 연구에 대한 실험 동물로서 기초 자료를 제공할 수 있을 것임을 보여준다.

• Nutrition Research and Practice
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• 제12권3호
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• pp.199-207
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• 2018

BACKGROUND/OBJECTIVES: Fermented Laminaria japonica (FL), a type sea tangle used as a functional food ingredient, has been reported to possess cognitive improving properties that may aid in the treatment of common neurodegenerative disorders, such as dementia. MATERIALS/METHODS: We examined the effects of FL on scopolamine (Sco)- and ethanol (EtOH)-induced hippocampus-dependent memory impairment, using the Passive avoidance (PA) and Morris water maze (MWM) tests. To examine the underlying mechanisms associated with neuroprotective effects, we analyzed acetylcholine (ACh) and acetylcholinesterase (AChE) activity, brain tissue expression of muscarinic acetylcholine receptor (mAChR), cAMP response element binding protein (CREB) and extracellular signal-regulated kinases 1/2 (ERK1/2), and immunohistochemical analysis, in the hippocampus of mice, compared to current drug therapy intervention. Biochemical blood analysis was carried out to determine the effects of FL on alanine transaminase (ALT), aspartate transaminase (AST), and triglyceride (TG) and total cholesterol (TC) levels. 7 groups (n = 10) consisted of a control (CON), 3 Sco-induced dementia and 3 EtOH-induced dementia groups, with both dementia group types containing an untreated group (Sco and EtOH); a positive control, orally administered donepezil (Dpz) (4mg/kg) (Sco + Dpz and EtOH + Dpz); and an FL (50 mg/kg) treatment group (Sco + FL50 and EtOH + FL50), orally administered over the 4-week experimental period. RESULTS: FL50 significantly reduced EtOH-induced increase in AST and ALT levels. FL50 treatment reduced EtOH-impaired step-through latency time in the PA test, and Sco- and EtOH-induced dementia escape latency times in the MWM test. Moreover, anticholinergic effects of Sco and EtOH on the brain were reversed by FL50, through the attenuation of AChE activity and elevation of ACh concentration. FL50 elevated ERK1/2 protein expression and increased p-CREB (ser133) in hippocampus brain tissue, according to Western blot and immunohistochemistry analysis, respectively. CONCLUSION: Overall, these results suggest that FL may be considered an efficacious intervention for Sco- and EtOH-induced dementia, in terms of reversing cognitive impairment and neuroplastic dysfunction.

• Journal of Ginseng Research
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• 제45권6호
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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 Ginseng Research
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• 제47권3호
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• pp.458-468
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• 2023

Background: As a complication of Type II Diabetes Mellitus (T2DM), the etiology, pathogenesis, and treatment of cognitive dysfunction are still undefined. Recent studies demonstrated that Ginsenoside Rg1 (Rg1) has promising neuroprotective properties, but the effect and mechanism in diabetes-associated cognitive dysfunction (DACD) deserve further investigation. Methods: After establishing the T2DM model with a high-fat diet and STZ intraperitoneal injection, Rg1 was given for 8 weeks. The behavior alterations and neuronal lesions were judged using the open field test (OFT) and Morris water maze (MWM), as well as HE and Nissl staining. The protein or mRNA changes of NOX2, p-PLC, TRPC6, CN, NFAT1, APP, BACE1, NCSTN, and Ab1-42 were investigated by immunoblot, immunofluorescence or qPCR. Commercial kits were used to evaluate the levels of IP3, DAG, and calcium ion (Ca²⁺) in brain tissues. Results: Rg1 therapy improved memory impairment and neuronal injury, decreased ROS, IP3, and DAG levels to revert Ca²⁺ overload, downregulated the expressions of p-PLC, TRPC6, CN, and NFAT1 nuclear translocation, and alleviated Aβ deposition in T2DM mice. In addition, Rg1 therapy elevated the expression of PSD95 and SYN in T2DM mice, which in turn improved synaptic dysfunction. Conclusions: Rg1 therapy may improve neuronal injury and DACD via mediating PLC-CN-NFAT1 signal pathway to reduce Aβ generation in T2DM mice.