• Journal of Ginseng Research
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• v.47 no.4
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• pp.583-592
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• 2023

Background: Alcohol is one of the most commonly used psychoactive drugs. Due to its addictive characteristics, many people struggle with the side effects of alcohol. Korean Red Ginseng (KRG) is a traditional herbal medicine that is widely used to treat various health problems. However, the effects and mechanisms of KRG in alcohol-induced responses remain unclear. Therefore, the purpose of this study was to investigate the effects of KRG in alcohol-induced responses. Methods: We investigated two aspects: alcohol-induced addictive responses and spatial working memory impairments. To determine the effects of KRG in alcohol-induced addictive responses, we performed conditioned place preference tests and withdrawal symptom observations. To assess the effects of KRG in alcohol-induced spatial working memory impairment, Y-maze, Barnes maze, and novel object recognition tests were performed using mice after repeated alcohol and KRG exposure. To investigate the potential mechanism of KRG activity, gas chromatography-mass spectrometry and western blot analysis were performed. Results: KRG-treated mice showed dose-dependent restoration of impaired spatial working memory following repeated alcohol exposure. Furthermore, withdrawal symptoms to alcohol were reduced in mice treated with KRG and alcohol. The PKA-CREB signaling pathway was activated after alcohol administration, which was reduced by KRG. However, the levels of inflammatory cytokines were increased by alcohol and decreased by KRG. Conclusion: Taken together, KRG may alleviate alcohol-induced spatial working memory impairments and addictive responses through anti-neuroinflammatory activity rather than through the PKA-CREB signaling pathway.

• The Korean Journal of Physiology and Pharmacology
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• v.28 no.3
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• pp.239-252
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• 2024

Dexmedetomidine displays multiple mechanisms of neuroprotection in ameliorating ischemic brain injury. In this study, we explored the beneficial effects of dexmedetomidine on blood-brain barrier (BBB) integrity and neuroinflammation in cerebral ischemia/reperfusion injury. Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) for 1.5 h and reperfusion for 24 h to establish a rat model of cerebral ischemia/reperfusion injury. Dexmedetomidine (9 ㎍/kg) was administered to rats 30 min after MCAO through intravenous injection, and SB203580 (a p38 MAPK inhibitor, 200 ㎍/kg) was injected intraperitoneally 30 min before MCAO. Brain damages were evaluated by 2,3,5-triphenyltetrazolium chloride staining, hematoxylin-eosin staining, Nissl staining, and brain water content assessment. BBB permeability was examined by Evans blue staining. Expression levels of claudin-5, zonula occludens-1, occludin, and matrix metalloproteinase-9 (MMP-9) as well as M1/M2 phenotypes-associated markers were assessed using immunofluorescence, RT-qPCR, Western blotting, and gelatin zymography. Enzyme-linked immunosorbent assay was used to examine inflammatory cytokine levels. We found that dexmedetomidine or SB203580 attenuated infarct volume, brain edema, BBB permeability, and neuroinflammation, and promoted M2 microglial polarization after cerebral ischemia/reperfusion injury. Increased MMP-9 activity by ischemia/reperfusion injury was inhibited by dexmedetomidine or SB203580. Dexmedetomidine inhibited the activation of the ERK, JNK, and p38 MAPK pathways. Moreover, activation of JNK or p38 MAPK reversed the protective effects of dexmedetomidine against ischemic brain injury. Overall, dexmedetomidine ameliorated brain injury by alleviating BBB permeability and promoting M2 polarization in experimental cerebral ischemia/reperfusion injury model by inhibiting the activation of JNK and p38 MAPK pathways.

• Journal of Life Science
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• v.30 no.12
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• pp.1078-1084
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• 2020

Protaetia brevitarsis seulensis is an insect belonging to the order Coleoptera. This insect is reported to contain large amounts of physiologically active substances useful for liver protective effect and improvements in blood circulation as well as a broad source of edible protein. Antimicrobial peptides (AMPs) are found in a variety of species, from microorganisms to mammals, and play an important role in the innate immune systems of living things. Microglia are the main source of proinflammatory cytokines and nitric oxide (NO) in the central nervous system. Activated microglia secrete large amounts of neuroinflammatory mediators (e.g., TNF-α, NO, and ROS), which are the main cause of neuronal cell death. In the present study, we investigated the inhibitory effect of Protaetiamycine 6 (PKARKLQKLSAYKTTLRN-NH2), an AMP derived from Protaetia brevitarsis seulensis, on LPS-induced neuroinflammation in BV-2 microglia. Protaetiamycine 6 significantly inhibited NO production without cytotoxicity and decreased the expression levels of inducible NO synthase and cyclooxygenase-2. In addition, Protaetiamycine 6 also reduced the production of neuroinflammatory cytokines on activated BV-2 microglia. These results suggest that Protaetiamycine 6 could be a good source of functional substance to prevent neuroinflammation and neurodegenerative diseases.

• Fisheries and Aquatic Sciences
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• v.17 no.1
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• pp.27-35
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• 2014

Marine brown algae have been identified as a rich source of structurally diverse bioactive compounds. Whether Myagropsis yendoi ethanolic extracts (MYE) inhibit inflammatory responses was investigated using lipopolysaccharide (LPS)-stimulated microglia BV-2 cells. MYE inhibited LPS-induced nitric oxide (NO) production in a dose-dependent manner and suppressed the expression of inducible nitric oxide synthase in BV-2 cells. MYE also reduced the production of pro-inflammatory cytokines in LPS-stimulated BV-2 cells. LPS-induced nuclear factor-${\kappa}B$ (NF-${\kappa}B$) transcriptional activity and NF-${\kappa}B$ translocation into the nucleus were significantly inhibited by MYE treatment through preventing degradation of the inhibitor ${\kappa}B-{\alpha}$. Moreover, MYE inhibited the phosphorylation of AKT, ERK, JNK, and p38 mitogen-activated protein kinase in LPS-stimulated BV-2 cells. These results indicate that MYE is a potential source of therapeutic or functional agents for neuroinflammatory diseases.

• Mass Spectrometry Letters
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• v.5 no.3
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• pp.70-78
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• 2014

Microglia are the confined immune cells of the central nervous system (CNS). In response to injury or infection, microglia readily become activated and release proinflammatory mediators that are believed to contribute to microglia-mediated neurodegeneration. In the present study, inflammation was induced in the immortalized murine microglial cell line BV-2 by lipopolysaccharide (LPS) treatment. We firstly performed phosphoproteomics analysis and phosphoinositide lipidomics analysis with LPS activated microglia in order to compare phosphorylation patterns in active and inactive microglia and to detect the pattern of changes in phosphoinositide regulation upon activation of microglia. Mass spectrometry analysis of the phosphoproteome of the LPS treatment group compared to that of the untreated control group revealed a notable increase in the diversity of cellular phosphorylation upon LPS treatment. Additionally, a lipidomics analysis detected significant increases in the amounts of phosphoinositide species in the LPS treatment. This investigation could provide an insight for understanding molecular mechanisms underlying microglia-mediated neurodegenerative diseases.

• Journal of Korean Medicine for Obesity Research
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• v.22 no.1
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• pp.77-85
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• 2022

While the Coronavirus disease 2019 (COVID-19) pandemic is gradually turning into an endemic disease, concerns about post COVID-19 conditions (Long COVID) are emerging. Obesity is a major risk factor for severe complications of COVID-19, and COVID-19 has a wide range of effects on obesity and metabolic function. This paper aims to examine the interaction between COVID-19 and obesity, the effects and mechanisms of long COVID on obesity, and the role of Korean medicine on long COVID-related obesity. Obesity may worsen with cardiometabolic damage and psychosocial insecurity during COVID-19 and long COVID-induced neuroinflammation, systemic inflammation, mitochondrial dysfunction, and hypoxia also may aggravate obesity. Korean Medicine treatments, which have been widely used to treat obesity, have the potential to improve obesity in the era of long COVID by intervening in these mechanisms.

• Journal of Life Science
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• v.29 no.4
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• pp.402-409
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• 2019

Korean red ginseng made from steaming and drying fresh ginseng has long been used as a traditional herbal medicine due to its effects on the immune, endocrine, and central nerve systems and its anti-inflammatory activity. In this study, we investigated the molecular mechanism responsible for the anti-inflammatory effects of a formulated Korean red ginseng extract (RGE) in response to lipoteichoic acid (LTA), a cell wall component of gram-positive bacteria. RGE inhibited LTA-induced nitric oxide (NO) secretion and inducible nitric oxide synthase (iNOS) expression in BV-2 microglial cells, without affecting cell viability. RGE also inhibited nuclear translocation of nuclear factor kappa B ($NF-{\kappa}B$) p65 and degradation of $I{\kappa}B-{\alpha}$. In addition, RGE increased the expression of heme oxygenase-1 (HO-1) in a dose-dependent manner, and the inhibitory effect of RGE on iNOS expression was abrogated by small interfering RNA-mediated knockdown of HO-1. Moreover, RGE induced nuclear translocation of nuclear factor E2-related factor 2 (Nrf2), a transcription factor that regulates HO-1 expression. Furthermore, the phosphoinositide-3-kinase (PI-3K) inhibitor and mitogen-activated protein kinase (MAPK) inhibitors suppressed RGE-mediated expression of HO-1, and RGE enhanced the phosphorylation of Akt, extracellular signal-regulated kinases (ERKs), p38, and c-JUN N-terminal kinases (JNKs). These results suggested that RGE suppressed the production of NO, a proinflammatory mediator, by inducing HO-1 expression via PI-3K/Akt- and MAPK-dependent signaling in LTA-stimulated microglia. The findings indicate that RGE could be used for the treatment of neuroinflammation induced by grampositive bacteria and that it may have therapeutic potential for various neuroinflammation-associated disorders.

• Nutrition Research and Practice
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• v.12 no.3
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• pp.191-198
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• 2018

BACKGROUD/OBJECTIVES: Neuroinflammation plays critical role in neurodegenerative disorders, such as Alzheimer's disease (AD). We investigated the effect of three licorice varieties, Glycyrhiza uralensis, G. glabra, and Shinwongam (SW) on a mouse model of inflammation-induced memory and cognitive deficit. MATERIALS/METHODS: C57BL/6 mice were injected with lipopolysaccharide (LPS; 2.5 mg/kg, intraperitoneally) and orally administrated G. uralensis, G. glabra, and SW extract (150 mg/kg/day). SW, a new species of licorice in Korea, was combined with G. uralensis and G. glabra. Behavioral tests, including the T-maze, novel object recognition and Morris water maze, were carried out to assess learning and memory. In addition, the expressions of inflammation-related proteins in brain tissue were measured by western blotting. RESULTS: There was a significant decrease in spatial and objective recognition memory in LPS-induced cognitive impairment group, as measured by the T-maze and novel object recognition test; however, the administration of licorice ameliorated these deficits. In addition, licorice-treated groups exhibited improved learning and memory ability in the Morris water maze. Furthermore, LPS-injected mice had up-regulated pro-inflammatory proteins, such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2, interleukin-6, via activation of toll like receptor 4 (TLR4) and nuclear factor-kappa B ($NF{\kappa}B$) pathways in the brain. However, these were attenuated by following administration of the three licorice varieties. Interestingly, the SW-administered group showed greater inhibition of iNOS and TLR4 when compared with the other licorice varieties. Furthermore, there was a significant increase in the expression of brain-derived neurotrophic factor (BDNF) in the brain of LPS-induced cognitively impaired mice that were administered licorice, with the greatest effect following SW treatment. CONCLUSIONS: The three licorice varieties ameliorated the inflammation-induced cognitive dysfunction by down-regulating inflammatory proteins and up-regulating BDNF. These results suggest that licorice, in particular SW, could be potential therapeutic agents against cognitive impairment.

• 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.

• 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.