• Journal of the Korea Academia-Industrial cooperation Society
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• v.20 no.2
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• pp.286-293
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• 2019

Alzheimer's disease (AD) is a neurodegenerative disease caused by accumulation of amyloid beta ($A{\beta}$) in the brain. In the present study, we investigated the neuroprotective effects of four flavonoids such as kaempferol, kaempferol-3-O-glucoside, quercetin, and quercetin-3-${\beta}$-D-glucoside against neuronal apoptosis induced by $A{\beta}$ in SH-SY5Y neuronal cells. Treatment with $A{\beta}$ decreased cell viability compared to the non-treated normal group. However, treatment with the four flavonoids increased cell viability in SH-SY5Y cells treated with $A{\beta}$. In addition, we measured the expression of apoptosis-related proteins such as Bcl-2-associated X protein (Bax) and cleaved caspase-9. Treatment with the four flavonoids down-regulated Bax and cleaved caspase-9 in $A{\beta}$-treated SH-SY5Y neuronal cells. Overall, the results of the present study demonstrated the neuroprotective effect of flavonoids by anti-apoptotic activity in $A{\beta}$-induced SH-SY5Y neuronal cells. These results suggest that these four flavonoids would be useful therapeutic and prevention agents for AD.

• Korean Journal of Biological Psychiatry
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• v.8 no.1
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• pp.62-70
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• 2001

Alzheimer's disease(AD) is associated with a characteristic neuropathology. The major hallmarks of AD are senile plaques (SPs) and neurofibrillary tangles(NFTs). ${\beta}$-amyloid protein($A{\beta}$) is derived from the proteolysis of amyloid precursor protein(APP) and then converted to SPs. Mature SPs produce cytotoxicity through direct toxic effects and activation of microglia and complement. NFTs are composed of paired helical filaments(PHFs) including abnormally phosphorylated form of the microtubule-associated protein(MAP) tau and increased tau level in cerebrospinal fluid may be observed in most AD. The aggregation of $A{\beta}$ and tau formation are thought to be a final common pathway of AD. Acetylcholine, dopamine, serotonin, GABA and their receptors are associated with AD. Especially, decreased nicotinic acetylcholine receptors(nAChRs) in AD are reported. Genetic lesions associated with AD are mutations in the structural genes for the APP located on chromosome 21, presenilin(PSN)1 located on chromosome 14 and PSN2 located on chromosome 1. Also, trisomy 21, Apo-E gene located on chromosome 19, PMF locus, low density lipoprotein receptor-related protein and ${\alpha}$-macroglobulin increase risk of AD. In this article, we will review about the neurobiology of AD and some newly developed research areas.

• Journal of Oriental Neuropsychiatry
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• v.12 no.2
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• pp.157-171
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• 2001

Astrocytes are glial cells that play a major role in the inflammation observed in Alzheimer's disease (AD). Upon stimulation from various agents, these cells adopt a reactive phenotype, a morphological hallmark in AD pathology, during which they themselves may produce still more inflammatory cytokines. Substance P (SP) can stimulate secretion of tumor necrosis $factor-\;{\alpha}$ $(TNF-\;{\alpha})$ from astrocytes stimulated with lipopolysaccharide (LPS). Here I report that Sunghyangjungkisan- ga- pogokyoung(Sgp) can modulate cytokines secretion from primary cultures of rat astrocytes. Sgp $(10\;to\;1000\;{\mu}g/ml)$ significantly inhibited the $TNF-\;{\alpha}$ secretion by astrocytes stimulated with LPS and SP. Interleukin-1 (IL-1) has been shown to elevate $TNF-\;{\alpha}$ secretion from LPS-stimulated astrocytes while having no effect on astrocytes in the absence of LPS. Treatment of Sgp $(10\;to\;1000\;{\mu}g/ml)$ to astrocytes stimulated with both LPS and SP decreased IL-1 secretion significantly. The secretion of $TNF-\;{\alpha}$ by LPS and SP in astrocytes was progressively inhibited with increasing amount of IL-1 neutralizing antibody. Neurodegenerative processes in AD are thought to be driven in part by the deposition of ${\beta}\;-amyloid\;(A\;{\beta})$, a 39- to 43-amino acid peptide product resulting from an alternative cleavage of amyloid precursor protein. Sgp $(10\;to\;1000\;{\mu}g/ml)$ significantly inhibited the $TNF-\;{\alpha}$ secretion by astrocytes stimulated with $A-{\beta}-$and IL-1. These results suggest that Sgp may inhibit $TNF-\;{\alpha}$ secretion by inhibiting IL-1 secretion and that Sgp has an antiinflammatory activity in AD brain

• Korean Journal of Pharmacognosy
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• v.44 no.3
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• pp.263-268
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• 2013

The protective role against oxidative stress under cellular system using C6 glioma cells was studied using the ethyl acetate (EtOAc) fraction, luteolin (1), and luteolin-7-glucoside (2) of Taraxacum coreanum. C6 glioma cells showed low cell viability and high generation of reactive oxygen species (ROS) by the treatment with generator of hydrogen peroxide ($H_2O_2$) and amyloid beta ($A{\beta}_{25-35}$). However, the treatment of the EtOAc fraction attenuated the cellular oxidative stress, resulting in significant elevation of cell viability. In addition, the production of ROS formation was also decreased by the treatment of the EtOAc fraction. Compounds 1 and 2 were isolated from the EtOAc fraction, and the protective effect was evaluated. Compounds 1 and 2 led to the increase of cell viability and decrease of production of ROS against oxidative stress by $H_2O_2$ and $A{\beta}_{25-35}$. The present study indicated that the EtOAc fraction, compounds 1 and 2 from T. coreanum demonstrated protective effects against oxidative stress, suggesting the preventive role against neurodegenerative diseases.

• Food Science and Preservation
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• v.14 no.2
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• pp.213-219
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• 2007

To develop an anti-dementia agent with potential therapeutic value in the protection of neuronal cells, we selected a water extract of Helianthus annuus seed for analysis. We measured acetylcholinesterase inhibitory activity in the extract, and analyzed the protective effect of the extract on neuronal cell death induced by hydrogen peroxide, or amyloid ${\beta}-peptide$, of SH-SY5Y neuroblastoma cells. The result showed that the extinct exerted protective effects of 83%, 72% and 53% respectively, on cell death induced by 100M, 200M, and 500M hydrogen peroxide. Also, when 50M of amyloid ${\beta}-peptide$ was added to the cells, the extract showed a protective effect (up to 80%) on cell death. Overall, the results showed that the H. annuus extract inhibited acetylcholinesterase activity in a dose-dependent manner, and the extract also strongly protected against cell death induced by hydrogen peroxide or amyloid ${\beta}-peptide$.

• Molecules and Cells
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• v.46 no.11
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• pp.675-687
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• 2023

Accumulation of pathogenic amyloid-β disrupts the tight junction of retinal pigment epithelium (RPE), one of its senescence-like structural alterations. In the clearance of amyloid-β, the autophagy-lysosome pathway plays the crucial role. In this context, mammalian target of rapamycin (mTOR) inhibits the process of autophagy and lysosomal degradation, acting as a potential therapeutic target for age-associated disorders. However, efficacy of targeting mTOR to treat age-related macular degeneration remains largely elusive. Here, we validated the therapeutic efficacy of the mTOR inhibitors, Torin and PP242, in clearing amyloid-β by inducing the autophagy-lysosome pathway in a mouse model with pathogenic amyloid-β with tight junction disruption of RPE, which is evident in dry age-related macular degeneration. High concentration of amyloid-β oligomers induced autophagy-lysosome pathway impairment accompanied by the accumulation of p62 and decreased lysosomal activity in RPE cells. However, Torin and PP242 treatment restored the lysosomal activity via activation of LAMP2 and facilitated the clearance of amyloid-β in vitro and in vivo. Furthermore, clearance of amyloid-β by Torin and PP242 ameliorated the tight junction disruption of RPE in vivo. Overall, our findings suggest mTOR inhibition as a new therapeutic strategy for the restoration of tight junctions in age-related macular degeneration.

• The Korean Journal of Physiology and Pharmacology
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• v.24 no.1
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• pp.39-46
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• 2020

Alzheimer's disease (AD) is the most common neurodegenerative disorder causing dementia worldwide, and is mainly characterized by aggregated β-amyloid (Aβ). Increasing evidence has shown that plant extracts have the potential to delay AD development. The plant sterol β-Sitosterol has a potential role in inhibiting the production of platelet Aβ, suggesting that it may be useful for AD prevention. In the present study, we aimed to investigate the effect and mechanism of β-Sitosterol on deficits in learning and memory in amyloid protein precursor/presenilin 1 (APP/PS1) double transgenic mice. APP/PS1 mice were treated with β-Sitosterol for four weeks, from the age of seven months. Brain Aβ metabolism was evaluated using ELISA and Western blotting. We found that β-Sitosterol treatment can improve spatial learning and recognition memory ability, and reduce plaque load in APP/PS1 mice. β-Sitosterol treatment helped reverse dendritic spine loss in APP/PS1 mice and reversed the decreased hippocampal neuron miniature excitatory postsynaptic current frequency. Our research helps to explain and support the neuroprotective effect of β-Sitosterol, which may offer a novel pharmaceutical agent for the treatment of AD. Taken together, these findings suggest that β-Sitosterol ameliorates memory and learning impairment in APP/PS1 mice and possibly decreases Aβ deposition.

• YAKHAK HOEJI
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• v.49 no.2
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• pp.168-173
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• 2005

Alzheimers disease (AD) is the most prevalent form of neurodegenerations associated with aging in the human population. This disease is characterized by the extracellular deposition of beta-amyloid (A ${\beta}$) peptide in cerebral plaques. The A ${\beta}$ peptide is derived from the ${\beta}$-amyloid precursor protein ( ${\beta}$APP). Photolytic processing of ${\beta}$APP by ${\beta}$-secretase(beta-site APP-cleaving enzyme, BASE) and ${\gamma}$-secretase generates the A ${\beta}$ peptide. Several lines of evidence support that A ${\beta}$-induced neuronal cell death is major mechanisms of development of AD. Accordingly, the ${\beta}$-and ${\gamma}$-secretase have been implicated to be excellent targets for the treatment of AD. We previously found that sesaminol glucosides have improving effect on memory functions through anti-oxidative mechanism. In this study, to elucidate possible other mechanism (inhibition of ${\beta}$-and ${\gamma}$-secretase) of sesaminol glucosides, we examined the improving effect of sesaminol glucosides in the scopolamine (1 mg/kg/mouse)-induced memory dysfunction using water maze test in the mice. Sesaminol glucosides (3.75, 7.5 mg/kg/6ml/day p.o., for 3 weeks) reversed the latency time, distance and velocity by scopolamine in dose dependent manner. Next, ${\beta}$-and ${\gamma}$-secretase activities were determined in different regions of brain. Sesaminol glucosides dose-dependently attenuated scopolamine-induced ${\beta}$-secretase activities in cortex and hippocampous and ${\gamma}$-secretase in cortex. This study therefore suggests that sesaminol glucosides may be a useful agent for prevention of the development or progression of AD, and its inhibitory effect on secretase may play a role in the improving action of sesaminol glucosides on memory function.

• Journal of Physiology & Pathology in Korean Medicine
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• v.23 no.2
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• pp.397-404
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• 2009

For standardization of LMK02 quality, Ginsenoside Rg3 of Red Ginseng and Decursin of Angelica gigas Nakai in the constituents of LMK02 were estimated as indicative components. From LMK02 water extract, has been used in vitro test for its beneficial effects on neuronal survival and neuroprotective functions, particularly in connection with APP-related dementias and Alzheimer's disease (AD). $A{\beta}$ oligomer derived from proteolytic processing of the ${\beta}$-amyloid precursor protein (APP), including the amyloid-${\beta}$ peptide ($A{\beta}$), play a critical role in the pathogenesis of Alzheimer's dementia. We determined that oligomer amyloid-${\beta}$ ($A{\beta}$) have a profound attenuation in the increase in rat hippocampus H19-7 cells from. Experimental evidence indicates that LMK02 protects against neuronal damage from cells, but its cellular and molecular mechanisms remain unknown. Using a hippocampus cell line on $A{\beta}$ oligomer-induced neuronal cytotoxicity, we demonstrated that LMK02 inhibits formation of $A{\beta}$ oligomer, which are the behavior, and possibly causative, feature of AD. In the Red Ginseng, the average amounts of Ginsenoside Rg3 were $47.04{\mu}g/g$ and $42.3{\mu}g/g$, 90 % of its weight were set as a standard value. And, in the Angelica gigas Nakai, the average amounts of Decursin were 2.71 mg/g and 2.44mg/g, 90 % of its weight were also set as a standard value. The attenuated $A{\beta}$ oligomer in the presence of LMK02 was observed in the conditioned medium of this $A{\beta}$ oligomer-induced cells under in vitro. In the cells, LMK02 significantly activated antiapoptosis and decreased the production of ROS. These results suggest that neuronal damage in AD might be due to two factors: a direct $A{\beta}$ oligomer toxicity and multiple cellular and molecular neuroprotective mechanisms, including attenuation of apoptosis and direct inhibition of $A{\beta}$ oligomer, underlie the neuroprotective effects of LMK02 treatment.

• 한국약용작물학회:학술대회논문집
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• 2006.04a
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• pp.121-135
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• 2006