• Journal of Life Science
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• v.26 no.6
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• pp.640-645
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• 2016

Microglial cells are immediately activated in the central nervous system in response to a variety of neuronal environmental changes, such as injuries or inflammation. In addition to the modulation of the intrinsic immune response, a key role of microglial cells is the phagocytosis of dying cells and cellular debris. In this study, the inhibitory effects of epigallocatechine-3-gallate (EGCG), a most abundant and active polyphenol component of green tea, on lipopolysaccharide (LPS)-induced microglial activation are determined. EGCG dose dependently suppressed LPS-induced nitric oxide production and the expression of inducible nitric oxide synthase (iNOS) in BV-2 microglial cells. EGCG are potent LPS-induced inhibitors of several pro-inflammatory cytokine expressions, such as TNF-α and IL-1β, in microglial cells. Furthermore, EGCG generally inhibits the induction of LPS-mediated microglial activation and potently inhibits the phagocytosis of LPS-stimulated BV2 microglia. Although the conditioned media from LPS-stimulated BV-2 cells caused the SN4741 cell death, that from the conditioned media of EGCG pretreated BV-2 cells did not diminish the viability of SN4741 cells. These results suggest EGCG, a green tea polyphenol, could be a promising available molecule for the modulation of harmful microglial activation.

• Journal of Life Science
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• v.28 no.11
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• pp.1332-1338
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• 2018

Activated microglia, induced by various pathogens, protect neurons and maintain homeostasis of the central nervous system (CNS). However, severe activation causes neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease because of the secretion of various neurotoxic molecules, such as nitric oxide (NO), prostaglandin (PG), and pro-inflammatory cytokines. Because chronic microglial activation endangers neuronal survival, negative regulators of microglial activation have been identified as potential therapeutic candidates for treatment of many neurological diseases. One potential source of these regulators is Locusta migratoria, a grasshopper of the Acrididae, usually 4-6 cm in size, belonging to the family of large insects in Acrididae. This grasshopper is an edible insect resource that can be consumed by humans as protein source or used for animal feed. The aim of the present study was to examine the inhibitory effects of a L. migratoria ethanol extract (LME) on the production of inflammatory mediators in LPS-stimulated BV-2 microglia cells. The extract significantly inhibited the NO, iNOS, COX-2, and pro-inflammatory cytokine ($TNF-{\alpha}$, IL-6 and $IL-1{\beta}$) levels in BV-2 microglia cell. Because the inhibition of microglial activation may be an effective solution for treating brain disorders like Alzheimer's and Parkinson's diseases, these results suggest that LME may be a potential therapeutic agent for the treatment of brain disorders induced by neuroinflammation.

• Journal of the Korea Society of Computer and Information
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• v.25 no.6
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• pp.165-170
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• 2020

In this paper, it was confirmed that scopoletin inhibits neuroinflammation induced by amyloid beta oligomer (Aβ_1-42) in microglial BV-2. The mechanisms of inflammatory cytokines and inflammatory mediators by scopoletin were identified. Alzheimer's disease is the most common neurodegenerative disease, but it is a disease whose specific etiology is unknown, and many studies are trying to solve it. We first measured the cell viability with the CCK-8 assay method to confirm that scopoletin and Aβ_1-42 are toxic to BV-2 cells. Expression levels of interleukin 1 beta (IL-1β), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and nuclear factor-κB (NF-κB) in inflammatory reactions induced by Aβ_1-42 with western blot were analyzed. The ANOVA assay was used to compare protein expression differences between BV-2 cells treated with Aβ_1-42 alone and BV-2 cells pretreated with Aβ_1-42 and scopoletin. Therefore, this study suggested that scopoletin is worth developing as a neuroinflammatory protection agent for Alzheimer's disease in the future.

• Korean Journal of Clinical Laboratory Science
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• v.52 no.3
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• pp.253-260
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• 2020

Alzheimer's disease (AD) is a chronic and progressive neurodegenerative disease that can be described by the occurrence of dementia due to a decline in cognitive function. The disease is characterized by the formation of extracellular and intracellular amyloid plaques. Amyloid beta (Aβ) is a hallmark of AD, and microglia can be activated in the presence of Aβ. Activated microglia secrete pro-inflammatory cytokines. Furthermore, S100A9 is an important innate immunity pro-inflammatory contributor in inflammation and a potential contributor to AD. This study examined the effects of metformin and α-LA on the inflammatory response and NLRP3 inflammasome activation in Aβ- and S100A9-induced BV-2 microglial cells. Metformin and α-LA attenuated inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). In addition, metformin and α-LA inhibited the phosphorylation of JNK, ERK, and p38. They activated the nuclear factor kappa B (NF-κB) pathway and the NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome. Moreover, metformin and α-LA reduced the marker levels of the M1 phenotype, ICAM1, whereas the M2 phenotype, ARG1, was increased. These findings suggest that metformin and α-LA are therapeutic agents against the Aβ- and S100A9-induced neuroinflammatory responses.

• Journal of Nutrition and Health
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• v.50 no.1
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• pp.25-31
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• 2017

Purpose: Neuroinflammation is mediated by activation of microglia implicated in the pathogenesis of neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease. Inhibition of neuroinflammation may be an effective solution to treat these brain disorders. Petalonia binghamiae is known as a traditional food, based on multiple biological activities such as anti-oxidant and anti-obesity. In present study, the anti-neuroinflammatory potential of Petalonia binghamiae was investigated in LPS-stimulated BV2 microglial cells. Methods: Cell viability was measured by MTT assay. Production of nitric oxide (NO) was examined using Griess reagent. Expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) was detected by Western blot analysis. Activation of nuclear factor ${\kappa}B$ ($NF-{\kappa}B$) signaling was examined by nuclear translocation of $NF-{\kappa}B$ p65 subunit and phosphorylation of $I{\kappa}B$. Results: Extract of Petalonia binghamiae significantly inhibited LPS-stimulated NO production and iNOS/COX-2 protein expression in a dose-dependent manner without cytotoxicity. Pretreatment with Petalonia binghamiae suppressed LPS-induced $NF-{\kappa}B$ p65 nuclear translocation and phosphorylation of $I{\kappa}B$. Co-treatment with Petalonia binghamiae and pyrrolidine duthiocarbamate (PDTC), an $NF-{\kappa}B$ inhibitor, reduced LPS-stimulated NO release compared to that in PB-treated or PDTC-treated cells. Conclusion: The present results indicate that extract of Petalonia binghamiae exerts anti-neuroinflammation activities, partly through inhibition of $NF-{\kappa}B$ signaling. These findings suggest that Petalonia binghamiae might have therapeutic potential in relation to neuroinflammation and neurodegenerative diseases.

• Journal of Life Science
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• v.25 no.6
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• pp.656-662
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• 2015

Natural products and natural product structures play a general and highly significant role in drug discovery and development process because it has various merits and potentials for new drug source that have extensive clinical experience, development time contraction, excellent stability and safety. In several neurological disorders, neuronal death and excessive activation of microglia (neuro-inflammation) are observed. A number of drug discovery-related neuronal cell death and neuro-inflammation was studied from natural products, respectively. However, until now, it has not been possible to study dual-protection molecules recorded in the Natural Product library. In the present study, using the natural product-derived library of the Institute for Korea Traditional Medical Industry, we investigated dual-protective molecules against glutamate (a classical excitatory neurotransmitter)-induced oxidative stress mediated neuronal cell death and LPS-induced excessive activated microglial cells (immune cells of the brain). Chrysophanol, extracted from Rheum palmatum, had dual-protective effects against both glutamate-induced neuronal cell death and LPS-induced NO production, triggering proinflammatory cytokines and microglia activation and resulting in neuroinflammation. Flow-cytometry analysis revealed that chrysophanol had a scavenger effect, scavenging glutamate- and LPS-induced reactive oxygen species (ROS) produced by neuronal and microglial cells, respectively. Based on the present study, chrysophanol may have an important protective role against neuronal cell death and neuroinflammation in the brain. The results may be helpful for studying drug development candidates for treating central nervous system disorders.

• Journal of the Korean Applied Science and Technology
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• v.36 no.2
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• pp.468-478
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• 2019

The aim of this study is to evaluate the efficacy of cordyceps militaris extracts for the improvement of cognitive dysfunction in PC12 and BV2 cells. Cordyceps militaris extracts was prepared by extracting with distilled water. Cell viability was assessed by MTT assay using PC12 cells and BV2 cells. Confirmed effects of L-glutamate induced cytotoxicity test, Acetylcoline (ACh) concentration, and Acetylcolinestase (AChE) activity in PC12 cells. Anti-inflammatory activities of cordyceps militaris extracts was measured through changes in the levels of nitric oxide (NO), and prostaglandin E2 ($PGE_2$) on lipopolysaccharide(LPS)-induced BV2 cell. In addition, we measured the expression of $NF-{\kappa}B$, p38, JNK, and caspase-3 in western blot analysis. Cordyceps militaris extracts showed no cytotoxicity at the concentrations of 1, 10, and $100{\mu}g/m{\ell}$ except for the concentration of $200{\mu}g/m{\ell}$. Cordyceps militaris extracts protected the cell and exhibited significant increases in the ACh concentration and a significant decrease in the AChE activity in L-glutamate induced PC12 cells. Moreover, cordyceps militaris extracts inhibited the productions NO, and PGE2 level and the protein expression of $NF-{\kappa}B$, p38, JNK, caspase-3 in LPS-induced BV2 cells. These results indicate that cordyceps militaris extracts possible prevented and improved cognitive dysfuction symptoms. Thus, cordyceps militaris extracts may be a novel natural material option for the improvement of cognitive dysfunction.

• Korean Journal of Pharmacognosy
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• v.49 no.1
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• pp.1-6
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• 2018

Six compounds, eupatilin (1), dammaradienyl acetate (2), glutinol acetate (3), $3{\beta}-acetoxyoleanan-12-one$ (4), taraxasterol (5) and quercetin-3,4'-dimethyl ether (6) were isolated from the aerial parts of Artemisia absinthium. The chemical structures of compounds 1-6 were determined by the basis of physico-chemical properties and spectroscopic methods such as 1D and 2D NMR. Among them, compounds 2-5 were isolated from this plant for the first time. The inhibitory effects of these isolated compounds against nitric oxide (NO) production in LPS-induced RAW264.7 cells or BV2 microglia were also examined. Among the tested compounds, compound 1, eupatilin, inhibited the production of NO in LPS-induced RAW264.7 cells and BV2 microglia, respectively.

• Korean Journal of Pharmacognosy
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• v.50 no.4
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• pp.291-298
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• 2019

Phlox subulata is a perennial herbaceous flower and is a member of the Polemoniaceae family. This plant is known to resist to various stresses including salt, drought, heat, and cold stresses. In this investigation, we evaluated the ant-inflammatory effect of the methanolic extract of P.subulata(PSM) on lipopolysaccharide(LPS)-induced RAW264.7 macrophages and BV2 microglia. PSM reduced the production of nitric oxide(NO) in LPS-stimulated both RAW264.7 and BV2 cells, but did not affect to the production of prostaglandin E2(PGE₂). It inhibited the expression of inducible nitric oxide synthase(iNOS) and cyclooxygenase(COX)-2 in both cells. In addition, PSM suppressed the production of pro-inflammatory cytokines including interleukin(IL)-6 and tumor necrosis factor(TNF)-α. These inhibitory effects were contributed by inactivation of nuclear factor kappa B(NF-κB) and mitogen-activated protein kinases(MAPKs) pathways by PSM. Thus, these results suggested that P.subulata can be a candidate material to treat inflammatory diseases.

• Journal of the Korean Society of Food Culture
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• v.38 no.5
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• pp.365-372
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• 2023

Ipomoea aquatic is a leafy vegetable of the Convolvulaceae family, and is a tropical plant widely inhabiting southern China and Southeast Asia, and is widely known as Morning Glory in the West. In this study, the anti-inflammatory effects of ethyl acetate extract from Ipomoea aquatic extracts (IAE) were tested against lipopolysaccharide (LPS)-induced activation microglia BV2 cells. The production of nitric oxide (NO) and cell viability were measured using the Griess reagent and MTT assay, respectively. Inflammatory cytokine [interleukin (IL)-6, tumor necrosis factor (TNF)-α, and interleukin-1β (IL-1β)] were detected qPCR in LPS induced BV-2 cells. Subsequently, nuclear factor (NF)-κB, mitogen-activated protein kinases (MAPKs), and nuclear factor erythroid-2-related factor 2 (Nrf2) were analyzed through western blot analyses and immunofluorescence. Ipomoea aquatic down-regulated of inflammatory markers and up-regulated anti-inflammatory and anti-oxidants in BV2 cells.