• The Journal of Korean Medicine
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• v.42 no.4
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• pp.120-132
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• 2021

Objectives: The prevalence of Parkinson's disease is on an upward trend along with an increase in the aging population but there is no available treatment that halts the progression of neurodegeneration. This study reports a numerical analysis on Donguibogam and suggests novel herbal drugs, which have never been researched before but found to be deemed effective in this study. Methods: Referring to 71 Korean medicine symptom terms that represent the symptoms of Parkinson's disease, 4170 prescriptions described in Donguibogam were classified into two groups based on whether their main effects were effective for Parkinson's disease or not. Comparing the two groups, the chi-square test was performed to select statistically significant herbs, while the t-test, Wilcoxon test, and descriptive statistics were performed to determine the appropriate dose. Results: One hundred and twenty-seven prescriptions effective for Parkinson's disease were identified. The chi-square test determined 17 herbs that are effective for symptomatic treatment. Among the medicinal herbs, the authors suggest Osterici seu Notopterygii Radix et Rhizoma, Ephedrae Herba, Aconiti Tuber, Myrrha, Sinomeni Caulis et Rhizoma, and Aconiti Kusnezoffii Tuber as herbal candidates that have never been studied for Parkinson's disease. Through the statistical tests, it was judged that the mean value of the dose of the entire prescription was the appropriate dose for each herb. Conclusions: Seventeen herbs were selected for Parkinson's disease and the appropriate daily dose were calculated. Furthermore, this study presented a new process that applies a statistical method to traditional medical literature and preselecting herbs deemed effective for specific diseases.

• Biomolecules & Therapeutics
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• v.31 no.3
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• pp.285-297
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• 2023

Alzheimer's disease (AD) is a neurodegenerative disease with progressive memory loss and the cognitive decline. AD is mainly caused by abnormal accumulation of misfolded amyloid β (Aβ), which leads to neurodegeneration via a number of possible mechanisms such as down-regulation of brain-derived neurotrophic factor-tropomyosin-related kinase B (BDNF-TRKB) signaling pathway. 7,8-Dihydroxyflavone (7,8-DHF), a TRKB agonist, has demonstrated potential to enhance BDNF-TRKB pathway in various neurodegenerative diseases. To expand the capacity of flavones as TRKB agonists, two natural flavones quercetin and apigenin, were evaluated. With tryptophan fluorescence quenching assay, we illustrated the direct interaction between quercetin/apigenin and TRKB extracellular domain. Employing Aβ folding reporter SH-SY5Y cells, we showed that quercetin and apigenin reduced Aβ-aggregation, oxidative stress, caspase-1 and acetylcholinesterase activities, as well as improved the neurite outgrowth. Treatments with quercetin and apigenin increased TRKB Tyr516 and Tyr817 and downstream cAMP-response-element binding protein (CREB) Ser133 to activate transcription of BDNF and BCL2 apoptosis regulator (BCL2), as well as reduced the expression of pro-apoptotic BCL2 associated X protein (BAX). Knockdown of TRKB counteracted the improvement of neurite outgrowth by quercetin and apigenin. Our results demonstrate that quercetin and apigenin are to work likely as a direct agonist on TRKB for their neuroprotective action, strengthening the therapeutic potential of quercetin and apigenin in treating AD.

• Genomics & Informatics
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• v.21 no.2
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• pp.23.1-23.9
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• 2023

The mammalian sirtuin family, consisting of SIRT1-SIRT7, plays a vital role in various biological processes, including cancer, diabetes, neurodegeneration, cardiovascular disease, cellular metabolism, and cellular homeostasis maintenance. Due to their involvement in these biological processes, modulating sirtuin activity seems promising to impact immuneand aging-related diseases, as well as cancer pathways. However, more understanding is required regarding the safety and efficacy of sirtuin-targeted therapies due to the complex regulatory mechanisms that govern their activity, particularly in the context of multiple targets. In this study, the interaction landscape of the sirtuin family was analyzed using a systems biology approach. A sirtuin protein-protein interaction network was built using the Cytoscape platform and analyzed using the NetworkAnalyzer and stringApp plugins. The result revealed the sirtuin family's association with numerous proteins that play diverse roles, suggesting a complex interplay between sirtuins and other proteins. Based on network topological and functional analysis, SIRT1 was identified as the most prominent among sirtuin family members, demonstrating that 25 of its protein partners are involved in cancer, 22 in innate immune response, and 29 in aging, with some being linked to a combination of two or more pathways. This study lays the foundation for the development of novel therapies that can target sirtuins with precision and efficacy. By illustrating the various interactions among the proteins in the sirtuin family, we have revealed the multifaceted roles of SIRT1 and provided a framework for their possible roles to be precisely understood, manipulated, and translated into therapeutics in the future.

• Journal of The Korean Society of Clinical Toxicology
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• v.21 no.2
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• pp.81-91
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• 2023

Purpose: Edible insect extracts have been used as an alternative source for medicinal supplements due to their significant antioxidative and anti-inflammatory activity. Recent studies have reported that anti-microbial peptides from insects have neuroprotective effects on dopamine toxins. The purpose of this study was to investigate the protective functions of mealworm (Tenebrio molitor) extract (MWE) on N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced cellular toxicity in SH-SY5Y neuroblastoma cells. Methods: Cellular toxicity induced by the MPTP toxin and the impact of MWE on cell survival were analyzed using MTT assays. DAPI staining was performed to observe apoptotic phenomena caused by MPTP. Changes in caspase-3 activity and protein expression were observed using enzyme activity assays and western blot assays, respectively. Results: MWE exerted significant antioxidant activity, which was measured by both DPPH and ABTS radical assays, with a dose-dependent relationship. Furthermore, MWE resulted in cellular proliferation in SHSY5Y cells in a dose-dependent manner. Furthermore, MWE pretreatment significantly inhibited MPTP-induced cytotoxicity, with a dose-dependent relationship. The morphological characteristics of apoptosis and increased reactive oxygen species induced by MPTP were also significantly reduced by MWE pretreatment. Conclusion: MWE treatment significantly attenuated MPTP-induced changes in the levels of proteins associated with apoptosis, such as caspase-3 and PARP. These findings suggest that MWE exerts neuroprotective effects on human neuroblastoma SH-SY5Y cells subject to MPTP-induced dopaminergic neurodegeneration.

• Journal of Korean Medicine Rehabilitation
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• v.19 no.2
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• pp.73-88
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• 2009

Objectives : Neuronal changes that result from treadmill exercise for patients with Parkinson's disease(PD) have not been well documented, although some clinical and laboratory reports suggest that regular exercise may produce a neuroprotective effect and restore dopaminergic and motor functions. However, it is not clear if the improvements are due to neuronal alterations within the affected nigrostriatal region or result from a more general effect of exercise on affect areas and motivation. In this study, we demonstrate that motorized treadmill exercise improves the neuronal outcomes in rodent models of PD. Methods : We used a chronic mouse model of parkinsonism, which was induced by injecting male C57BL/6 mice with 10 doses(Every 12 hour) of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (30 mg/kg) and probenecid (20 mg/kg) over 5 days. These mice were able to sustain an exercise training program on a motorized rodent treadmill at a speed of 18 m/min, $0^{\circ}$ of inclination, 40 min/day, 5 days/week for 4 weeks. At the end of exercise training, we extracted the brain and compared their neuronal and neurochemical changes with the control(saline and sedentary) mice groups. Synphilin protein is the substance that manifestly reacts with ${\alpha}$-synuclein. In this study, we used Synphilin as a manifest sign of recovery from neurodegeneration. We analyze the brain stems of the substantia nigra and striatum region using the western blotting technique. Results : There were no expression of synphilin in the saline-induced groups. The addition of MPTP(1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) greatly accelerated synphilin expression which meant an aggregation of ${\alpha}$-synuclein. But, the MPTP-induced treadmill exercise group showed significantly lower expression than the MPTP-induced sedentary group. This means treadmill exercise has a definite effect on the decrease of ${\alpha}$-synuclein aggregation. Conclusions : In this study, our results suggest that treadmill exercise promoted the removal of the aggregation of ${\alpha}$-synuclein, resulting in protection against disease development and blocks the apoptotic process in the chronic parkinsonian mice brain with severe neurodegeneration.

• Korean Journal of Food Science and Technology
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• v.48 no.5
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• pp.508-514
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• 2016

Effects of the ethyl acetate fraction from gomchwi (Ligularia fischeri) extract against high $glucose/H_2O_2-induced$ oxidative stress and in vitro neurodegeneration were investigated to confirm the physiological property of the extract. The ethyl acetate fraction of gomchwi extract showed the highest total phenolic contents than the other solvent fractions. An anti-hyperglycemic activity of the ethyl acetate fraction was evaluated using the ${\alpha}-glucosidase$ inhibitory assay, and the half maximal inhibitory concentration ($IC_{50}$) value for ${\alpha}-glucosidase$ was found to be $727.64{\mu}g/mL$. In addition, the ethyl acetate fraction showed excellent 2,2'-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) diammonium salt radical scavenging activity, and inhibition of malondialdehyde production. The ethyl acetate fraction also decreased intracellular reactive oxygen species, whereas neuronal cell viability against high glucose/$H_2O_2$-induced cytotoxicity was found to be increased. Finally, 3,5-dicaffeoylquinic acid as a main phenolic compound in the ethyl acetate fraction was analyzed by high-performance liquid chromatography. These results suggest that gomchwi might be a good natural source of functional materials to prevent diabetic neurodegeneration.

• Biomolecules & Therapeutics
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• v.23 no.3
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• pp.251-260
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• 2015

Propofol is an anesthetic agent that gained wide use because of its fast induction of anesthesia and rapid recovery post-anesthesia. However, previous studies have reported immediate neurodegeneration and long-term impairment in spatial learning and memory from repeated neonatal propofol administration in animals. Yet, none of those studies has explored the sex-specific long-term physical changes and behavioral alterations such as social (sociability and social preference), emotional (anxiety), and other cognitive functions (spatial working, recognition, and avoidance memory) after neonatal propofol treatment. Seven-day-old Wistar-Kyoto (WKY) rats underwent repeated daily intraperitoneal injections of propofol or normal saline for 7 days. Starting fourth week of age and onwards, rats were subjected to behavior tests including open-field, elevated-plus-maze, Y-maze, 3-chamber social interaction, novel-object-recognition, passive-avoidance, and rotarod. Rats were sacrificed at 9 weeks and hippocampal protein expressions were analyzed by Western blot. Results revealed long-term body weight gain alterations in the growing rats and sex-specific impairments in spatial (female) and recognition (male) learning and memory paradigms. A markedly decreased expression of hippocampal NMDA receptor GluN1 subunit in female- and increased expression of AMPA GluR1 subunit protein expression in male rats were also found. Other aspects of behaviors such as locomotor activity and coordination, anxiety, sociability, social preference and avoidance learning and memory were not generally affected. These results suggest that neonatal repeated propofol administration disrupts normal growth and some aspects of neurodevelopment in rats in a sex-specific manner.

• Clinical and Experimental Pediatrics
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• v.48 no.4
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• pp.425-432
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• 2005

Purpose : Polyglutamine diseases are a group of diseases caused by the expansion of a polyglutamine tract in the protein. The present study was performed to verify if polyglutamine disease transgenic Drosophila models show similar dysfunctions as are seen in human patients. Methods : Polyglutamine disease transgenic Drosophila were tested for their climbing ability. And using genetic methods, the effects of anti-apoptotic gene bcl-2 and chemical chaperones on neurodegeneration were observed. Also, spinocerebellar ataxia 2 (SCA2) transgenic Drosophila lines were generated for future studies. Results : Expanded forms of spinocerebellar ataxia 3 (SCA3) transgenic protein causes characteristic locomotor dysfunction when expressed in the nervous system of Drosophila but the anti-apoptotic gene bcl-2 shows no evidence of ameliorating the deleterious effect of the expanded protein. However, Glycerol, a chemical chaperone, seemed to reduce the toxicity, at least in the eyes of the transgenic flies. The level SCA2 expression is too weak in the transgenic SCA2 Drosophila for evaluation. Conclusion : SCA3 transgenic Drosophila show ataxic behavior as observed in human patients. Chemical chaperones such as glycerol may prove beneficial in this class of genetic disease, which has no current method of cure.

• Journal of Life Science
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• v.19 no.4
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• pp.520-525
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• 2009

Early onset of Batten disease (EBD), one of the most lethal neurodegenerative storage disorders of childhood, is caused by inactivating mutations in the Ceroid Lipofuscinosis, Neuronal (CLN1) gene. Neurogranin, a calmodulin-binding protein, is expressed in the brain and participates in the protein kinase C (PKC) signaling pathway. While oxidative stress is the suggested cause of neurodegeneration in EBD, its molecular mechanism(s) remains obscure. In this research, we examined the levels of neurogranin in the brain mRNA of wild-type (WT) mice and EBD knockout (KO) mice, as well as the proteins. We also performed neuronal cultures to measure the expression levels of neurgranin and phosphorylated-neurogranin with or without oxidative stress inducers and anti-oxidants. Results showed that neurogranin in both EBD KO mice brain mRNA and protein extracts decreased in an age dependent manner. However, high amounts of phosphorylated-neurogranin were detected in the 6-month brain. This pattern was also confirmed by cultured neurospheres samples. Moreover, neurospheres treated with $H_2O_2$, an oxidative stress inducer, showed increased phosphorylated-neurogranin patterns. Interestingly, this pattern returned to normal status when treated with N-acetyl-L-cystein, an anti-oxidant, after $H_2O_2$ treatment was performed. Our results suggest that the phosphorylation of neurogranin is affected by oxidative stress status in EBD, and appropriate anti-oxidant treatment will relieve hyper-phosphorylation of neurogranin.

• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.5
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• pp.976-988
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• 2002

The aim of this study was to examine the memory and attention enhancement effect of YMG-1 and YMG-2, which are modified herbal extracts from Yukmijihwang-tang (YMJ). YMJ, composing six herbal medicine, has been used for restoring the normal functions of the body to consolidate the constitution, nourishing and invigorating the kidney functions for hundreds years in Asian countries. A series of studies reported that YMJ and its components enhance memory retention, protects neuronal cell from reactive oxygen attack and boost immune activities. Recently the microarray analysis suggested that YMG-1 protects neurodegeneration through modulating various neuron specific genes. A total of 55 subjects were divided into three groups according to the treatment of YMG-1 (n=20), YMG-2 (n=20) and control (C; n=15) groups. Before treatments, all of subjects were subjected to the assessments on neuropsychological tests of K-WAIS test, Rey-Kim memory test, and psychophysiological test of Event-Related Potential (ERP) during auditory oddball task and repeated word recognition task. They were repeatedly assessed with the same methods after drug treatment for 6 weeks. Although no significant effect of drug was found in Rey-Kim memory test, a significant interaction (P = .010, P < 0.05) between YMG-2 and C groups was identified in the scores digit span and block design, which are the subscales of K-WAIS. The very similar but marginal interaction (P = .064) between YMG-1 and C groups was found too. In ERP analysis, only YMG-1 group showed decreasing tendency of P300 latency during oddball task while the others tended to increase, and it caused significant interaction between session and group (p= .004). This result implies the enhancement of cognitive function in due to consideration of relationship between P300 latency and the speed of information processing. However, no evidence which could demonstrate the significant drug effect was found in neither amplitude or latency. These results come together suggest that YMG-1, 2 may enhance the attention, resulting in enhancement of memory processing. For elucidating detailed mechanism of YMG on learning and memory, the further studies are necessary.