• The Journal of Internal Korean Medicine
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• v.25 no.3
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• pp.482-491
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• 2004

Alzheimer's disease(AD) is a geriatric dementia that is widespread in old age. In the near future AD may be the biggest problem in public health service. Although a variety of oriental therapies in the study of Jimitang have been traditionally utilized for the treatment of AD, their pharmacological effects and active mechanisms have not been fully elucidated. This study in an investigation of effects of Jimitang on apoptotic cell death induced by CT105 overexpression in SK-N-SH neuroblastoma cell lines. DNA fragmentation, neurite outgrowth assay and LDH activity assay were examined. The regeneratory and inhibitory effects on Alzheimer's disease in pCT105-induced neuroblastoma cell lines by Jimitang water extract were examined. Findings from these experiments have shown that Jimitang inhibits the synthesis or activities of CT105, which has neurotoxicities and apoptotic activities in cell lines. In addition, pretreatment of $Jimitang(>50\;{\mu}g/mL\;for\;12\;hours)$ partially prevented CT(105)-induced cytotoxicity in SK-N-SH cell lines, and were inhibited by pretreatment. $Jimitang(>50\;{\mu}g/mL\;for\;12\;hours)$ repaired CT(105)-induced neurite outgrowth when SK-N-SH cell lines were transfected with CT(105). Results of this study show that. in the Jimitang group, the apoptosis in the nervous system in inhibited, the repair against the degerneration of neuroblastoma cells by CT105 expression is promoted. In addition, Jimitang was found to inhibit DNA fragmentation induced by CT105 overexpression, and promote neurite outgrowth. These findings suggest that Jimitang is beneficial for the treatment of AD.

• The Journal of Internal Korean Medicine
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• v.27 no.3
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• pp.603-616
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• 2006

The water extract of Gamiyaengshinhwan (GYH), has been used in vitro tests for its beneficial effects on neuronal survival and neuroprotective functions, particularly in connection with CT105-related dementias and Alzheimer's disease(AD). CT105 derived from proteolytic processing of the $\beta$-amyloid precursor protein (APP), including the amyloid-$\beta$ peptide ($A{\beta}$), plays a critical role in the pathogenesis of Alzheimer's dementia. We determined that transfected overexpressing APP695 and $A{\beta}$ CT105 have a profound attenuation in the Increase in CT105 expressing neuro2A cells from GYH. Experimental evidence indicates that GYH protects against neuronal damage from cells, but its cellular and molecular mechanisms remain unknown. Using a neuroblastoma cell line stably expressing CT105-associated neuronal degeneration, we demonstrated that GYH inhibits formation of amyloid-$\beta$ fragment ($A{\beta}$ CT105). which are the characteristic, and possibly causative, features of AD. The decreased CT105 $A{\beta}$ in the presence of GYH was observed in the conditioned medium of this CT105-secreting cell line under in vitro. In the cells, GYH significantly attenuated mitochondrion-initiated apoptosis and decreased the activity of Bax, a key enzyme in the apoptosis cell-signaling cascade. These results suggest that neuronal damage in AD might be due to two factors: a direct CT05 toxicity and the apoptosis initiated by the mitochondria. Multiple cellular and molecular neuroprotective mechanisms, including attenuation of apoptosis and direct inhibition of CT105 aggregation, underlie the neuroprotective effects of GYH.

• The Korean Journal of Food And Nutrition
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• v.33 no.6
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• pp.614-623
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• 2020

The objective of this study was to produce a nutrient delivery system (NDS) using sialic acid extracted from edible bird's nest (EBN), which improves brain function in patients with Alzheimer's disease and Parkinson's disease, by affinity bead technology (ABT). The inhibitory activity of acetylcholinesterase (AChE) and pyramidal cells in the dentate gyrus of the hippocampus were analyzed to investigate the effect of a sialic acid NDS on Alzheimer's disease. Also, the effect of a sialic acid NDS on Parkinson's disease was evaluated by rota-rod test and pole test in an animal model. Among the groups treated with donepezil, EBN, and sialic acid NDS, the AChE activity was the lowest in the sialic acid NDS-treated group. The results of the hippocampus analysis of the rat model confirmed that the sialic acid NDS inhibited amyloid-beta accumulation depending upon the concentration. Also, the sialic acid NDS group showed more improvement in motor deterioration than the1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced group in both the rota-rod test and pole test. Therefore, the sialic acid NDS had an effect of protecting not only Alzheimer's disease by inhibiting AChE and amyloid-beta accumulation, but Parkinson's disease by preventing neurotoxicity induced by MPTP.

• BMB Reports
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• v.44 no.2
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• pp.135-139
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• 2011

Chronic alcohol consumption contributes to numerous diseases, including cancers, cardiovascular diseases, and liver cirrhosis. Epidemiological studies have shown that excessive alcohol consumption is a risk factor for dementia. Along this line, Alzheimer's disease (AD) is the most common form of dementia and is caused by the accumulation of amyloid-$\beta$ ($A{\beta}$ plaques in neurons. In this study, we hypothesized that chronic ethanol consumption is associated with pathological processing of APP in AD. To investigate the relationship between chronic alcohol consumption and $A{\beta}$ production, brain samples from rats fed an alcohol liquid diet for 5 weeks were analyzed. We show that the expression levels of APP, BACE1, and immature nicastrin were increased in the cerebellum, hippocampus, and striatum of the alcohol-fed group compared to the control group. Total nicastrin and PS1 levels were induced in the hippocampus of alcohol-fed rats. These data suggest that the altered expression of APP and $A{\beta}$-producing enzymes possibly contributes to the chronic alcohol consumption-mediated pathogenesis of AD.

• Journal of the Korean Applied Science and Technology
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• v.29 no.4
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• pp.552-560
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• 2012

Drug delivery technologies are patent protected formulation technologies that modify drug release profile, absorption, distribution, and elimination for the benefit of improving product efficacy and safety, as well as patient convenience and compliance. The most commonly used transdermal system is the skin patch using various types of technologies. Compared with other method of dosage, it is possible to use for a long term. It is also possible to stop the drug dosage are stop if the drug dosage lead to side effect. Polysaccharide, such as karaya gum and locust bean gum(LBG)/water-soluble chitosan oligomer(WSCO) were selected as base materials of TDS. Also, these polymers were characterized in terms of enhancers, tacrine contents. Among these polysaccharide, the permeation rate of karaya gum matrix was fastest in tacrine such as lipophilic drug in vitro. We used glycerin, PEG 400, and PEG 800 as enhancers. Therefore, transdermal absorption of tacrine could be improved by changing vehicle composition or by using penetration enhancers. Especially it would be anticipated that the high permeation efficacy could be obtained by using vehicle that has enhancing effect for itself and by adding enhancers to it.

• Journal of Oriental Neuropsychiatry
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• v.14 no.2
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• pp.95-105
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• 2003

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, Radix Polygalae and Rhizoma Acori Graminei have been used for disease in relation to brain retrogression. We studied of anti-Alzheimer effect on CT105-induced neuroblastoma cell lines by Radix Polygalae(RP) and Rhizoma Acori Graminei(RAG) water extract. As the result of this study, In RP and RAG group, the apoptosis in the nervous system is inhibited, the repair against the degeneration of Neuroblastoma cells by CT105 expression is induced. These results indicate that In RP and RAG, RAG possess the strongest in inhibitory effect of apoptosis in the nervous system and repair effect against the degeneration of Neuroblastoma cells by CT105 expression.

• The Journal of Internal Korean Medicine
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• v.42 no.5
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• pp.1082-1093
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• 2021

Objective: Alzheimer's disease is characterized by progressive, irreversible brain damage and cognitive decline. Although the diagnosis and treatment of the prodromal symptoms of dementia are important, no treatment for mild cognitive impairment has been currently established. Herein, we report the case of an 80-year-old female patient with memory complaints treated with Gugijihwang-tang, a traditional Korean medicine herbal formula, as an add-on medication. Case Presentation: The patient was diagnosed with mild cognitive impairment based on clinical examinations using the Mini-Mental State Examination (MMSE), the Consortium to Establish a Registry for Alzheimer's Disease (CERAD), Activities of Daily Living (ADL) Scale, Global Deterioration (GDR) Scale, and Clinical Dementia Rating (CDR) Scale. She was treated with Gugijihwang-tang bis in die for 12 months while continuing her original medications, including 5-mg donepezil and 590-mg acetyl-l-carnitine. The MMSE score in the Korean Version of the CERAD Assessment Packet increased from 21 to 27 during the 12-month treatment period, and the CERAD 2 score increased from 33 to 62. The instrumental ADL scale score improved from 11 to 5. Other clinical examination results also showed improvement. The patient was satisfied and experienced no significant adverse events related to the Gugijihwang-tang treatment. Conclusion: This case suggests that Gugijihwang-tang could be considered as a treatment method for patients with mild cognitive impairment.

• Food Science of Animal Resources
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• v.43 no.4
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• pp.612-624
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• 2023

The gut-brain axis encompasses a bidirectional communication pathway between the gastrointestinal microbiota and the central nervous system. There is some evidence to suggest that probiotics may have a positive effect on cognitive function, but more research is needed before any definitive conclusions can be drawn. Inflammation-induced by lipopolysaccharide (LPS) may affect cognitive function. To confirm the effect of probiotics on oxidative stress induced by LPS, the relative expression of antioxidant factors was confirmed, and it was revealed that the administration of probiotics had a positive effect on the expression of antioxidant-related factors. After oral administration of probiotics to mice, an intentional inflammatory response was induced through LPS i.p., and the effect on cognition was confirmed by the Morris water maze test, nitric oxide (NO) assay, and interleukin (IL)-1β enzyme-linked immunosorbent assay performed. Experimental results, levels of NO and IL-1β in the blood of LPS i.p. mice were significantly decreased, and cognitive evaluation using the Morris water maze test showed significant values in the latency and target quadrant percentages in the group that received probiotics. This proves that intake of these probiotics improves cognitive impairment and memory loss through anti-inflammatory and antioxidant mechanisms.

• Dementia and Neurocognitive Disorders
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• v.21 no.4
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• pp.117-125
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• 2022

Background and Purpose: Medication adherence is essential for effective medical treatment. However, it is challenging for cognitively impaired patients. We investigated whether an automated telephone reminder service improves medication adherence and reduces the decline of cognitive function in isolated patients with cognitive impairment. Methods: This was a single-center, randomized clinical trial. We enrolled mild cognitive impairment (MCI) or Alzheimer's disease (AD) patients who lived alone or with a cognitively impaired spouse. We provided an automated telephone reminder service for taking medication to the intervention group for 6 months. The control group was provided with general guidelines for taking the medication every month. The participants underwent neuropsychological assessment at the beginning and end of the study. Statistical significance was tested using nonparametric Wilcoxon rank sum and Wilcoxon matched-pairs signed-rank tests. Results: Thirty participants were allocated randomly to groups, and data for 29 participants were analyzed. The mean age was 79.6 (standard deviation, 6.0) years and 79.3% of the participants were female. There was no significant difference in medication adherence between the 2 groups. However, a subgroup analysis among participants with more than 70% response rates showed better medication adherence compared to the control group (intervention: 94.6%; control: 90.2%, p=0.0478). There was no significant difference in the change in cognitive function between the 2 groups. Conclusions: If a patient's compliance is good, telephone reminders might be effective in improving medication adherence. It is necessary to develop reminder tools that can improve compliance for cognitively impaired patients.

• The Korean Journal of Nuclear Medicine
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• v.30 no.3
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• pp.299-314
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• 1996

The purpose of the present study was to validate the use of tissue radioactivity ratios instead of regional metabolic rates for the assessment of regional metabolic changes in Alzheimer's disease(AD) with [$^{18}F$]FDG PET and to examine the correlation of ratio indices with the severity of cognitive impairment in AD. Thirty-seven AD Patients(age $68{\pm}9 yrs$, $mean{\pm}s.d.$; 36 probable and 1 definite AD), 28 patients with dementia of non-Alzheimer type(age $66{\pm}7 yrs$), and 17 healthy controls(age $66{\pm}4 yrs$) underwent [$^{18}F$]FDG PET imaging. Two simplified radioactivity ratio indices were calculated from 37-66 min image: region-to-cerebellar radioactivity ratio(RCR) and a composite radioactivity ratio(a ratio of radioactivity in the most typically affected regions over the least typically affected regions: CRR). Local cerebral metabolic rate for glucose(LCMRglu) was also measured using a three-compartment, five-parameter tracer kinetic model. The ratio indices were significantly lower in AD patients than in controls(RCR in temporoparietal cortex, $0.949{\pm}0.136$ vs. $1.238{\pm}0.129$, p=0.0004; RCR in frontal cortex, $1.027{\pm}0.128$ vs. $1.361{\pm}0.151$, p<0.0001; CRR, $0.886{\pm}0.096$ vs. $1.032{\pm}0.042$. p=0.0024). On the RCR analysis, 86% of AD patients showed a pattern of bilateral temporoparietal hypometabolism with or without frontal involvement; hypometabolism was unilateral in 11% of the patients. When bilateral temporoparietal hypometabolism was considered to be suggestive of AD, the sensitivity and specificity of the RCR analysis for the differential diagnosis of AD were 86% and 73%, respectively. The RCR was correlated significantly with the macroparameter K [$K_1k_3/(k_2+k_3)$] (r=0.775, p<0.0001) and LCMRglu(r=0.633, p=0.0002) measured using the kinetic model. In patients with AD, both average RCR of cortical association areas and CRR were correlated with Mini-Mental Status Examination(r=0.565, p=0.0145; r=0.642, p=0.0031, respectively), Clinical Dementia Rating(r=-0.576, p=0.0124; r=-0.591, p=0.0077), and total score of Mattis Dementia Rating Scale (r=0.574, p=0.0648; r=0.737, p=0.0096). There were also significant correlations between memory and language impairments and corresponding regional RCRs. The results suggest that the [$^{18}F$]FDG PET ratio indices, RCR and CRR, reflect global and regional metabolic rates and correlate with the severity of cognitive impairment in AD. The simplified ratio analysis may be clinically useful for the differential diagnosis and serial monitoring of the disease.