• Korean Journal of Acupuncture
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• v.40 no.3
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• pp.90-98
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• 2023

Objectives : Parkinson's disease (PD) is the second most common neurodegenerative disorder worldwide and is characterized by the loss of the dopaminergic neurons in the substantia nigra (SN). In a previous in vitro study, we demonstrated that Sihogyeji-tang (SG), Sihosogan-tang (SS), and Sihocheonggan-tang (SC) have the potential to be candidate medicines for PD. This study aimed to compare the neuroprotective effect of SG, SS, and SC using 1-methyl-4-phenyl-1,2,3,6-tetrahydrophridine (MPTP)-induced PD mouse model. Methods : Eight-week-old male C57BL/6 mice were intraperitoneally administered with 30 mg/kg of MPTP for 5 days and orally administered SG, SS and SC for 12 days from the first MPTP injection. Motor function was assessed using the pole test and the rotarod test. Dopaminergic neuronal survival in the SN and striatum was evaluated through tyrosine-hydroxylase immunohistochemistry. Results : MPTP administration resulted in behavioral impairment and dopaminergic neuronal death in the SN and striatum. In the pole test, treatment with SG, SS, and SC alleviated the MPTP-induced motor dysfunction on day 5 and 12. In the rotarod test, SS and SG alleviated the MPTP-induced motor dysfunction on day 5, while only SS showed improvement on day 12. SS and SG significantly protected dopaminergic neurons in the SN from MPTP toxicity, and all three compounds (SG, SS, and SC) showed significant protection in the striatum. Notably, SS demonstrated superior efficacy in suppressing MPTP-induced motor dysfunction and dopaminergic neuronal death compared to SG and SC. Conclusions : These findings suggest that SS is the most effective formula among SG, SS, and SC for PD, indicating its potential role in the treatment of PD.

• The Journal of Korean Medicine
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• v.25 no.4
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• pp.95-107
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• 2004

Objective : The inappropriate or excessive apoptosis has been known to be associated with neurodegenerative disorders including intracranial hemorrhage(ICH). Paeoniae radix, in traditional Korean medicine, has played its role as blood­nourisher and yin-astringent. In the present study, the effect of Paeoniae radix on the inhibition of neurodegeneration in the brain of rats after artificial ICH and on the resulting apoptosis was investigated. Methods : 30 rats were divided into 6 equal groups ; the sham-operation group, the hemorrhage-induction group, the hemorrhage-induction with 10, 50, 100, and 200 mg/kg Paeoniae radix-treated group, respectively. Stereotactic surgery was performed and collagenase was infused to induce ICH in the region of CA1 of hippocampus of rats. The sham group took only saline infusion. For 7 days after the surgery, 4 testing groups had intraperitoneal injections of Paeoniae radix extract. The step-down inhibitory avoidance task, measurement of neurodegeneration degree in the CA1 region of the hippocampus, and detection of caspase-3 and newly generated cells in the dentate gyrus were done after animal sacrifice. Results : Rats receiving Paeoniae radix extract showed increased latency time in the inhibitory avoidance task. The extension of neuron-deprived areas in the CA1 region was significantly suppressed in the Paeonia treated groups. Also expressions of caspase-3 in the CA1 region and cortex were significantly inhibited in the Paeonia treated groups. The cell proliferation was evaluated by means of BrdU methods and proved to be decreased in the Paeonia treated groups. Conclusion : These results suggest that Paeoniae radix has potential to suppress short-tenn memory loss after devastating neurologic accidents. Also it was proved that Paeoniae radix has a neuroprotective effect and alleviates central nervous complications following intracerebral hemorrhage. Furthermore, it may imply that this medicinal plant can be widely used for vascular dementia and other neurodegenerative disorders.

• Journal of Korean Biological Nursing Science
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• v.10 no.2
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• pp.176-183
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• 2008

Purpose: The purpose of this study was to identify the effect of Environmental Enrichment (EE) on improvement of motor function in animal models of Parkinson's Disease. Methods: Male C57BL6 mice weighing 25-30 g, at the age of 12 wks were used in this study. The animals were injected MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridin, 20 mg/kg in saline, i.p.) 4 times a day at every 2 hr, and raised in EE cage for 14 days. On day 14, after behavior test, all mice were sacrificed for immunohistochemistry. All values were expressed as means$\pm$S.E.M. Statistical significance was evaluated using a one way ANOVA followed by Sheffe test. Results: There was a significant difference between the experimental group and the control group in the behavior test. Also EE significantly reduced of TH positive cell loss in Substantia nigra pars compacta as compared to the result of MPTP treatment. Conclusion: Based on these findings, it is reasonable to assume that the environmental enrichment prevents dopaminergic neuronal loss and improves disarrangement of motor function and behavioral disability induced by MPTP.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.50 no.1
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• pp.85-91
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• 2017

Alzheimer's disease (AD) is a progressive neurodegenerative disorder of insidious onset that causes gradual loss of memory and cognitive function, and it is the most common form of dementia in the elderly. AD is characterized by neuritic plaques and neurofibrillary tangles in the brain, together with loss of neuronal cells. The major neuropathological hallmark of AD is the accumulation of extracellular neurotoxic ${\beta}-amyloid$ ($A{\beta}$) peptides, such as $A{\beta}1-42$, in the brain. In the present study, we investigated the effect of sargachromenol (SCM), sargaquinoic acid (SQA) and sargahydroquinoic acid (SHQA) isolated from Sargassum serratifoilum ethanol extract (SSE) on $A{\beta}$ production in vitro using APP751-transfected Chinese hamster ovary cells (CHO-751). CHO-751 cells were treated with various concentrations of SSE, SCM, SQA and SHQA, and the level of extracellular $A{\beta}1-42$ was evaluated by enzyme-linked immunosorbent assay. SSE and SHQA reduced the production of $A{\beta}1-42$ in CHO-751 cells. Therefore, SHQA isolated from S. serratifolium has potential as an inhibitor of neurotoxic $A{\beta}$ peptide production.

• Journal of Ginseng Research
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• v.44 no.4
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• pp.603-610
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• 2020

Background: Depression is a common neuropsychiatric disease that shows astrocyte pathology. Ginsenoside Rf (G-Rf) is a saponin found in Panax ginseng which has been used to treat neuropsychiatric diseases. We aimed to investigate antidepressant properties of G-Rf when introduced into the L-alphaaminoadipic acid (L-AAA)-infused mice model which is representative of a major depressive disorder that features diminished astrocytes in the brain. Methods: L-AAA was infused into the prefrontal cortex (PFC) of mice to induce decrease of astrocytes. Mice were orally administered G-Rf (20 mg/kg) as well as vehicle only or imipramine (20 mg/kg) as controls. Depression-like behavior of mice was evaluated using forced swimming test (FST) and tail suspension test (TST). We observed recovery of astroglial impairment and increased proliferative cells in the PFC and its accompanied change in the hippocampus by Western blot and immunohistochemistry to assess the effect of G-Rf. Results: After injection of L-AAA into the PFC, mice showed increased immobility time in FST and TST and loss of astrocytes without significant neuronal change in the PFC. G-Rf-treated mice displayed significantly more decreased immobility time in FST and TST than did vehicle-treated mice, and their immobility time almost recovered to those of the sham mice and imipramine-treated mice. G-Rf upregulated glial fibrillary acidic protein (GFAP) expression and Ki-67 expression in the PFC reduced by L-AAA and also alleviated astroglial change in the hippocampus. Conclusion: G-Rf markedly reversed depression-like behavioral changes and exhibited protective effect against the astrocyte ablation in the PFC induced by L-AAA. These protective properties suggest that G-Rf might be a therapeutic agent for major depressive disorders.

• Journal of Ginseng Research
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• v.35 no.2
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• pp.138-148
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• 2011

Exponential rise in the use of mobile communication devices has generated health concerns due to radiofrequency (RF) exposure due to its close proximity to the head. Calcium binding proteins like calretinin regulate the levels of calcium ($Ca^{2+}$) which plays an important role in biological systems. Ginseng is known for maintaining equilibrium in the human body and may play a beneficial radioprotectant role against electromagnetic field (EMF) exposure. In the present study, we evaluated the radioprotective effects of red ginseng (RG) extract in a mouse model. Calretinin (CR) expression was measured using a free-floating immunohistochemical method in the hippocampus of mice after 835 MHz EMF exposure for 5 h/d for 5 d at specific absorption rate=1.6 W/kg for the different experimental groups. The control animals were treated with NaCl while the experimental animals received 10 mg/kg ginseng, or 30 mg/kg; EMF exposed mice were also treated with NaCl, 10 mg/kg ginseng (E10), or 30 mg/kg (E30). Decreases in CR immunoreactivity (IR) along with loss of CA1 and CA3 interneurons and infragranular cells were observed in the ENaCl group while such losses were not observed in the E10 and E30 groups. CR IR significantly increased in the RG-treated group compared to control and EMF-exposed groups treated with NaCl. The study demonstrates that RG extract can serve as a radioprotective agent that maintains $Ca^{2+}$ homeostasis and prevents neuronal loss in the brain hippocampal region caused by RF exposure.

• Molecules and Cells
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• v.37 no.11
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• pp.767-776
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• 2014

Alzheimer's disease (AD) is clinically characterized with progressive memory loss and cognitive decline. Synaptic dysfunction is an early pathological feature that occurs prior to neurodegeneration and memory dysfunction. Mounting evidence suggests that aggregation of amyloid-${\alpha}$ ($A{\alpha}$) and hyperphosphorylated tau leads to synaptic deficits and neurodegeneration, thereby to memory loss. Among the established genetic risk factors for AD, the ${\varepsilon}4$ allele of apolipoprotein E (APOE) is the strongest genetic risk factor. We and others previously demonstrated that apoE regulates $A{\alpha}$ aggregation and clearance in an isoform-dependent manner. While the effect of apoE on $A{\alpha}$ may explain how apoE isoforms differentially affect AD pathogenesis, there are also other underexplored pathogenic mechanisms. They include differential effects of apoE on cerebral energy metabolism, neuroinflammation, neurovascular function, neurogenesis, and synaptic plasticity. ApoE is a major carrier of cholesterols that are required for neuronal activity and injury repair in the brain. Although there are a few conflicting findings and the underlying mechanism is still unclear, several lines of studies demonstrated that apoE4 leads to synaptic deficits and impairment in long-term potentiation, memory and cognition. In this review, we summarize current understanding of apoE function in the brain, with a particular emphasis on its role in synaptic plasticity and the underlying cellular and molecular mechanisms, involving low-density lipoprotein receptor-related protein 1 (LRP1), syndecan, and LRP8/ApoER2.

• BMB Reports
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• v.47 no.8
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• pp.424-432
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• 2014

The defining feature of Parkinson's disease is a progressive and selective demise of dopaminergic neurons. A recent report on Parkinson's disease animal model demonstrates that poly (ADP-ribose) (PAR) dependent cell death, also named parthanatos, is accountable for selective dopaminergic neuronal loss. Parthanatos is a programmed necrotic cell death, characterized by PARP1 activation, apoptosis inducing factor (AIF) nuclear translocation, and large scale DNA fragmentation. Besides cell death regulation via interaction with AIF, PAR molecule mediates diverse cellular processes including genomic stability, cell division, transcription, epigenetic regulation, and stress granule formation. In this review, we will discuss the roles of PARP1 activation and PAR molecules in the pathological processes of Parkinson's disease. Potential interaction between PAR molecule and Parkinson's disease protein interactome are briefly introduced. Finally, we suggest promising points of therapeutic intervention in the pathological PAR signaling cascade to halt progression in Parkinson's disease.

• Proceedings of the Korean Society of Medical Physics Conference
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• 2003.09a
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• pp.76-76
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• 2003

Purpose: To assess clinical proton MR spectroscopy (MRS) as a noninvasive method for evaluating tumor malignancy at 3T high field system. Methods: Using 3T MRI/MRS system, localized water-suppressed single-voxel technique in patients with brain tumors was employed to evaluate spectra with peaks of N-acetyl aspartate (NAA), choline-containing compounds (Cho), creatine/phosphocreatine (Cr) and lactate. On the basis of Cr, these peak areas were quantificated as a relative ratio. Results: The variation of metabolites measurements of the designated region in 10 normal volunteers was less than 10%. Normal ranges of NAA/Cr and Cho/Cr ratios were 1.67$\pm$018 and 1.16:1:0.15, respectively. NAA/Cr ratio of all tumor tissues was significantly lower than that of the normal tissues (P=0.005). Cho/Cr ratio of high-grade gliomas was significantly higher than that of low-grade gliomas (P= 0.001), Except 4 menigiomas, lactate signal was observed in all tumor cases. Conclusions: The present study demonstrated that the neuronal degradation or loss was observed in all tumor tissues. Higher grade of brain tumors was correlated with higher Cho/Cr ratio, indicating a significant dependence of Cho levels on malignancy of gliomas. This results suggest that clinical proton MR spectroscopy could be useful to predict tumor malignancy. Acknowledgement: This study was supported by a grant of the Mid and Long Term Nuclear R/D Plan Program, Ministry of Science and Technology, Republic of Korea.

• Nutritional Sciences
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• v.8 no.4
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• pp.231-236
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• 2005

This study investigated the changes in the neuronal nitric oxide synthase (nNOS) and nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) activities during food restriction in the rat brain such as cerebral cortex, cerebellum, caudate pautamen and hypothalamus. The rats were placed on a restricted feeding schedule consisting of half the ad libitum quantity for 3 days and 1, 2, 4, 6 and 9 weeks, and a free feeding schedule for 4 weeks. The loss of body weight peaked after 1 week of food restriction and persisted during the entire 9-week period of food restriction. The dramatic weight change in the first week ($12\%$) and the reduction in weight changes thereafter suggest that major adaptation changes occur early and body maintenance occurs subsequently. In the hypothalamus, the optical densities of the NADPH-d and nNOS immunoreactivities were found to be significantly higher in the 1-week and lower in the 9-week food restricted group than in the ad libitum fed control rats. In contrast, in the cerebral cortex, the optical densities of the NADPH-d- and nNOS-positive neurons were not changed significantly during the period of food restriction. This study provides the morphological evidence showing that food restriction has a significant effect on the nitric oxide synthesizing system of the hypothalamus.