• 한국키틴키토산학회지
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• 제23권4호
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• pp.220-227
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• 2018

Amyloid plaque is a product of aggregation of ${\beta}$-amyloid peptide ($A{\beta}$) and is an important factor in the pathogenesis of Alzheimer's Disease (AD). $A{\beta}$ is a major component of amyloid plaque and vascular deposits in the AD brain. The enzyme ${\beta}$-secretase is required for the production of $A{\beta}$; thus, prevention of the formation of $A{\beta}$ through the inhibition of ${\beta}$-secretase is a major focus in the study of the treatment of AD. In this study, we investigated ${\beta}$-secretase inhibitory activity of an Arctoscopus japonicus peptide. An Alcalase hydrolysate had the highest ${\beta}$-secretase inhibitory activity. A ${\beta}$-secretase inhibitory activity peptide was separated using ion exchange column chromatography (carboxy-methyl: CM, quaternary methyl ammonium: QMA) and reverse phase high performance liquid chromatography (RP-HPLC) on a C18 column. The $IC_{50}$ value of the purified peptide was $248.2{\pm}1.73{\mu}g/mL$. The ${\beta}$-secretase inhibitory peptide was identified as a six amino acid residue of Gly-Pro-Val-Gly-Ala-Pro (MW: 497.27 Da). In cell viability experiments, the final purified fraction, the carboxy-methyl ion exchange column fraction (CM-F1) showed no significant cytotoxic effect in SH-SY5Y cells at concentrations below $100{\mu}g/mL$ in 24 h. The results of this study suggest that peptides separated from Arctoscopus japonicus may be beneficial as ${\beta}$-secretase inhibitor compounds in functional foods.

• Journal of Medicine and Life Science
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• 제17권3호
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• pp.65-73
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• 2020

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a single-gene disease of the cerebral small blood vessels caused by mutations in the NOTCH3 gene on chromosome 19. Although CADASIL was known as a rare disease, recent research has suggested that the NOTCH variants could be found frequently even in the general population. The main clinical features included recurrent stroke, migraine, psychiatric symptoms, and progressive cognitive decline. On brain magnetic resonance imaging, patients with CADASIL showed multifocal white matter hyperintensity lesions, lacunar infarcts, microbleeds, and brain atrophy. Among them, lacunar infarcts and brain atrophy are important in predicting the clinical outcomes of patients with CADASIL. In the Jeju National University Hospital, we have diagnosed 213 CADASIL patients from 2004 to 2020. Most NOTCH3 mutations were located in exon 11 (94.4%), and p.Arg544Cys was the most common mutation. The mean age at diagnosis was 61.0±12.8 years. The most common presenting symptoms were ischemic stroke (24.4%), followed by cognitive impairment(15.0%), headache (8.9%), and dizziness(8.0%). Although the exact prevalence of CADASIL in Jeju is still unknown, the disease prevalence could be as high as 1% of the population considering the prevalence reported in Taiwan. Therefore, it is necessary to discover efficient biomarkers and genetic tests that can accurately screen and diagnose patients suspected of having CADASIL in this region. Ultimately, it is urgent to explore the exact pathogenesis of the disease to identify leading substances of treatment potential, and for this, multi-disciplinary research through active support from the Jeju provincial government as well as the national government is essential.

• 동의신경정신과학회지
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• 제32권4호
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• pp.345-378
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• 2021

Objectives: The purpose of this study was to investigate the recent trends of clinical research on acupuncture using electroencephalogram (EEG) as the outcome measurement. Methods: Nine domestic and foreign databases were searched to collect related studies published up to November 3, 2021. The participants, intervention, outcomes, results of the included studies were extracted and analyzed. Results: A total of 18 studies were selected. Neurological diseases and mental disorders were included in most studies, and vascular dementia were most frequently investigated. Electroacupuncture and body acupuncture intervention were most frequently conducted in seven studies. The most commonly used outcomes using EEG was EEG abnormality. However, in most studies there was accurate description of the EEG measurement. Most studies showed significant difference in EEG outcomes after intervention. The quality of included studies was poor. Conclusions: EEG as diagnostic markers and outcome measurements is increasingly studied. Standardized EEG measurement and the consistent EEG finding for specific diseases are needed to perform the future rigorous studies on EEG as diagnostic and outcome tools.

• Journal of Acupuncture Research
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• 제33권4호
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• pp.49-63
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• 2016

Objectives : This research was performed to investigate the effects of Jodeungsan pharmacopuncture(PA-J) of focal brain ischemia induced by middle cerebral artery occlusion(MCAO) in rats. Methods : The subjects were divided into 4 groups : control, acupuncture, pharmacopuncture PA-J1(11.43 mg / 250 g / $40{\mu}{\ell}$) and pharmacopuncture PA-J2(2.29 mg / 250 g / $40{\mu}{\ell}$). The focal brain ischemia was induced by intraluminal filament insertion into the middle cerebral artery. After 3 days of MCAO, Jodeungsan pharmacopuncture treatment was performed on the GB20, and the day after being treated with pharmacopuncture, the Morris water maze test was carried out on the assigned group. The series of processes were administered 6 times. Thereafter mGluR5, density of neuronal cell and ChAT were measured. Results : The results were as follows. 1. The distance to target significantly decreased in the 2nd trial of the Acu group on the water maze test for short-term memory. 2. The distance to target significantly decreased in the 4th trial of the PA-J2 group on the water maze test for long-term memory. 3. The intensity of mGluR5 significantly increased in the PA-J1 group compared with the control group. 4. The neuroprotective effect on the hippocampal CA1 significantly increased in the PA-J1 and PA-J2 groups compared with the control group. 5. The density of ChAT in the hippocampal CA1 significantly increased in the PA-J1 and PA-J2 groups compared with the control group. Conclusion : These results suggest that Jodeungsan pharmacopuncture may improve memory and cognitive impairment and also have neuroprotective effects on focal brain ischemia.

• Korean Journal of Acupuncture
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• 제19권2호
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• pp.63-78
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• 2002

Kupunggibodan(KU), Gamisamul-tang(GA) and Whangryunhaedok-tang(WH) are clinically the most popular prescriptions as an herbal medicine in the treatment of ischemia. In order to compare and evaluate their protective effects on the ischema-induced cognitive deficits by middle cerebral artery occlusion (MCAO), we examined its ability to improve ischemia-induced cell loss and impairements of learning and memory in the Morris water maze and eight-arm radial arm maze. Focal cerebral ischemia produced a marked cell loss, decrease in acetylcholinesterase(AchE) reactivity in the hippocampus, and learning and memory deficits in two behavioral tasks. Pretreatment with WH (100 mg/kg, p.o.) produced a substantial increase in acquisition in the Morris water maze. Pretreatment with KU increased the perfomance of the resention test in the Morris water maze. WH, KU and GA caused a significant improvement in choice accuracy in radial arm maze test. WH was superior to KU and GA in perfomance of the radial arm maze test. Consistent with behavioral data, staining with cresyl violet showed that pretreatments with WH, but not KU and GA significantly recovered the ischemia-induced cell loss in the hippcampal CA1 area. In addition, pretreatments with WH and KU recovered the ischemia-induced reduction of AchE reactivity in the hippocampal CA1 area. These results demonstrated that KU, GA and WH have protective effects against ischimea-induced learning and memory impairments and that the efficacy was the order of WH>KU>GA in tratment of ischemia induced memory deficits. The present studies provide an evidence of KU, GA and WH as putative treatment of vascular dementia. Supported by a fund from the Ministry of Health and Welfare(HMP-00-OO-04-0004), and the Brain Korea 21 Project from Korean Ministry of Education, Korea.

• Journal of Korean Neurosurgical Society
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• 제65권5호
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• pp.665-679
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• 2022

Objective : Patients with mild ischemic stroke experience various sequela and residual symptoms, such as anxious behavior and deficits in movement. Few approaches have been proved to be effective and safe therapeutic approaches for patients with mild ischemic stroke by acute stroke. Sildenafil (SIL), a phosphodiesterase-5 inhibitor (PDE5i), is a known remedy for neurodegenerative disorders and vascular dementia through its angiogenesis and neurogenesis effects. In this study, we investigated the efficacy of PDE5i in the emotional and behavioral abnormalities in rats with mild ischemic stroke. Methods : We divided the rats into four groups as follows (n=20, respectively) : group 1, naïve; group 2, middle cerebral artery occlusion (MCAo30); group 3, MCAo30+SIL-pre; and group 4, MCAo30+SIL-post. In the case of drug administration groups, single dose of PDE5i (sildenafil citrate, 20 mg/kg) was given at 30-minute before and after reperfusion of MCAo in rats. After surgery, we investigated and confirmed the therapeutic effect of sildenafil on histology, immunofluorescence, behavioral assays and neural oscillations. Results : Sildenafil alleviated a neuronal loss and reduced the infarction volume. And results of behavior task and immunofluorescence shown possibility that anti-inflammation process and improve motor deficits sildenafil treatment after mild ischemic stroke. Furthermore, sildenafil treatment attenuated the alteration of theta-frequency rhythm in the CA1 region of the hippocampus, a known neural oscillatory marker for anxiety disorder in rodents, induced by mild ischemic stroke. Conclusion : PDE5i as effective therapeutic agents for anxiety and movement disorders and provide robust preclinical evidence to support the development and use of PDE5i for the treatment of mild ischemic stroke residual disorders.