• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.5
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• pp.1178-1191
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• 2008

This experiment was designed to investigate the effect of the SSJHT hot water extract & ultra-fine Powder on Alzheimer's Disease Model Induced by ${\beta}A$. The effects of the SSJHT hot water extract on expression of IL-1RA, $IL-1{\beta}$$, IL-6, IL-10, $TNF-{\alpha}$, NOS-II, COX-2 mRNA and production of $IL-1{\beta}$, IL-6, $TNF-{\alpha}$ in BV2 microglial cell line treated by lipopolysacchaide(LPS). The effects of the SSJHT hot water extract & ultra-fine powder on (1) the behavior (2) expression of $IL-1{\beta}$, $TNF-{\alpha}$, MDA, CD68, CD11b and AChE (3) and the infarction area of the hippocampus in Alzheimer's diseased mice induced with ${\beta}A$ were investigated. The SSJHT hot water extract suppressed the expression of $IL-1{\beta}$, IL-6 and $TNF-{\alpha}$, NOS-II, COX-2 mRNA and increased IL-1RA, IL-10 in BV2 microglia cell line treated with LPS. The SSJHT hot water extract suppressed the production of $IL-1{\beta}$, IL-6, $TNF-{\alpha}$ significantly in BV2 microglial cell line treated with LPS. The SSJHT hot water extract & ultra-fine powder a significant inhibitory effect on the memory deficit was shown for the mice with Alzheimer's disease induced by ${\beta}A$ in the Morris water maze experiment, which measured step-through latency. The SSJHT hot water extract & ultra-fine powder suppressed the expression of $TNF-{\alpha}$$, $L-1{\beta}$ protein significantly in the microglial cell of mice with Alzheimer's disease induced by ${\beta}A$. The SSJHT hot water extract & ultra-fine powder reduced the MDA and suppressed the over-expression of CD68, CD11b in the mice with Alzheimer's disease induced by ${\beta}A$. The SSJHT hot water extract & ultra-fine powder significantly decreased AChE activity in the serum of the mice with Alzheimer's disease induced by ${\beta}A$. The SSJHT hot water extract & ultra-fine powder reduced infarction area of hippocampus. and controlled the injury of brain tissue in the mice with Alzheimer's disease induced by ${\beta}A$. The results suggest that the SSJHT hot water extract & ultra-fine powder may be effective for treatment of Alzheimer's disease. Investigation into the clinical use of the SSJHT hot water extract & ultra-fine powder for Alzheimer's disease is suggested for future research.

• Journal of Life Science
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• v.33 no.6
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• pp.455-462
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• 2023

During pregnancy, maternal immune activation (MIA) from infection increases the risk of neurodevelopmental diseases, including schizophrenia and autism spectrum disorders. MIA induced by polyinosinic-polycytidylic acid (poly (I:C)) and lipopolysaccharide (LPS) in animal experiments has led to offspring with abnormal behaviors and brain development. In addition, it has recently been reported that microglia, which reside in the brain and function as immune cells, play an important role in behavioral abnormalities and brain development in MIA-induced offspring. However, the underlying mechanism remains unclear. In this study, we investigated whether microglia-specific inhibition of GPR56, a member of the G protein-coupled receptor (GPCR) family, causes behavioral abnormalities in brain development. First, MIA induction did not affect the microglia population, but when examining the expression of microglial GRP56 in MIA-induced fetuses, GPR56 expression was inhibited between embryonic days 14.5 (E14.5) and E18.5 regardless of sex. Furthermore, microglial GPR56-suppressed mice showed abnormal behaviors in the MIA-induced offspring, including sociability deficits, repetitive behavioral patterns, and increased anxiety levels. Although abnormal cortical development such as that in the MIA-induced offspring were not observed in the microglial GPR56-suppressed mice, their brain activity was observed through c-fos staining. These results suggest that microglia-specific GPR56 deficiency may cause abnormal behaviors and could be used as a biomarker for the diagnosis and/or as a therapeutic target of behavioral deficits in MIA offspring.

• Journal of Microbiology and Biotechnology
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• v.28 no.9
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• pp.1443-1446
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• 2018

In the present study, we examined whether Lactobacillus johnsonii CJLJ103 (LJ) could alleviate cholinergic memory impairment in mice. Oral administration of LJ alleviated scopolamine-induced memory impairment in passive avoidance and Y-maze tasks. Furthermore, LJ treatment increased scopolamine-suppressed BDNF expression and CREB phosphorylation in the hippocampi of the brain, as well as suppressed $TNF-{\alpha}$ expression and $NF-{\kappa}B$ activation. LJ also increased BDNF expression in corticosterone-stimulated SH-SY5Y cells and inhibited $NF-{\kappa}B$ activation in LPS-stimulated microglial BV2 cells. However, LJ did not inhibit acetylcholinesterase activity. These findings suggest that LJ, a member of human gut microbiota, may mitigate cholinergic memory impairment by increasing BDNF expression and inhibiting $NF-{\kappa}B$ activation.

• Korean Journal of Food Science and Technology
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• v.53 no.3
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• pp.296-303
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• 2021

The antioxidant and anti-neuroinflammatory activities of water, 30, 70, and 100% ethanol extracts of leaves of three different species of bamboo (Phyllostachys nigra, P. bambusoides, and Sasa borealis) were investigated. The levels of total polyphenol and flavonoid were measured, and antioxidant activity was evaluated using various antioxidant assays (DPPH, ABTS, and FRAP). Lipopolysaccharide (LPS)-induced BV2 microglial cell activation was used to evaluate the anti-neuroinflammatory properties of the bamboo leaf extracts. Treatment with both aqueous and ethanolic extracts showed no cytotoxicity in BV-2 microglial cells. Pre-treatment of BV-2 cells with bamboo leaf extracts significantly inhibited LPS-induced excessive production of nitric oxide in a dose-dependent manner. Moreover, phytochemical analysis based on the extraction solvent showed that caffeic acid, p-coumaric acid, and tricin are the principal constituents of all three bamboo leaf extracts. Therefore, our findings suggest that bamboo leaf extract contains potent antioxidants and anti-neuroinflammatory compounds that can be used as potential therapeutic agents for the treat neuroinflammatory diseases.

• Journal of Life Science
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• v.30 no.4
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• pp.331-342
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• 2020

The suppression of neuroinflammatory responses in microglial cells can be considered a key target for improving the progression of neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD). Asparagus cochinchinensis has traditionally been used as a medicine to treat fever, cough, kidney disease, breast cancer, inflammatory diseases, and brain diseases. In this study, we investigated the neuroprotective mechanism of an aqueous extract from A. cochinchinensis root (AEAC), particularly its anti-inflammatory effects on lipopolysaccharide (LPS)-activated BV-2 microglial cells. BV-2 cells were treated with four different concentrations of AEAC. No significant toxicity was detected in BV-2 cells treated with AEAC. Nitric oxide (NO), cyclooxygenase-2 (COX-2) mRNA, and inducible nitric oxide synthase (iNOS) mRNA levels were 21% lower in the AEAC+LPS group than in the Vehicle+LPS group. Lower proinflammatory (TNF-α and IL-1β) and anti-inflammatory cytokine (IL-6 and IL-10) levels were also detected in the AEAC+LPS group than in the Vehicle+LPS group, albeit at varying rates. Moreover, the phosphorylation of mitogen-activated protein kinase (MAPK) members after LPS treatment was significantly recovered in the AEAC-pretreated group compared to the Vehicle+LPS group, enhancement of the phosphorylation of mitogen-activated protein kinase (MAPK) members after LPS treatment was significantly recovered in the AEAC-pretreated group, while cell cycle arrest at the G2/M phase caused by LPS treatment was less severe in the AEAC+LPS group. The increase in reactive oxygen species (ROS) generation induced by LPS treatment was also lower in the AEAC-pretreated group than in the Vehicle+LPS group. This is the first study to show that AEAC exerts anti-neuroinflammatory activity against LPS stimulation by regulating the MAPK signaling pathway, the cell cycle, and ROS production.

• The Korea Journal of Herbology
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• v.37 no.5
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• pp.83-88
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• 2022

Objectives : Jakyakgamcho-tang (JGT) has been traditionally used to treat muscular convulsion and pain in South Korea. According to recent studies, JGT has been reported to have anti-depression, anti-inflammation, anti-oxidative, anti-diabetics, anti-spasm and analgesic effects, but studies on its anti-neuroinflammatory and neuroprotective effect have not been deeply conducted. Thus, we investigated the anti-neuroinflammatory activity of JGT on lipopolysaccharide (LPS)-stimulated mouse microglia cells. Methods : To investigate the anti-neuroinflammatory effects of JGT on BV2 microglial cells, we examined the production of nitric oxide (NO) using griess assay, and mRNA expressions of pro-inflammatory cytokines such as interleukin (IL)-1𝛽, IL-6, and tumor necrosis factor (TNF)-𝛼 using real time RT-PCR. Furthermore, to determine the regulating mechanisms of JGT, we investigated the heme oxygenase (HO)-1 by real time RT-PCR. Results : Pre-treatment of JGT effectively decreased NO production in LPS-stimulated BV2 cells at concentrations without cytotoxicity. Additionally, JGT significantly suppressed the production of IL-1𝛽, IL-6, and TNF-𝛼 in LPS-stimulated BV2 cells. Furthermore, JGT activated the HO-1 expression, which is one of the immunomodulatory signaling molecules. And the abolishment of HO-1 by tin protoporphyrin IX (SnPP, the HO-1 inhibitor) reversed the anti- inflammatory activity of JGT in LPS-stimulated BV2 cells. Conclusions : Our results suggest that the JGT has anti-neuroinflammatory effect through the activation of HO-1 in LPS-stimulated BV2 cells. Thereby, JGT could expected to be used for the prevention and treatment of neurodegenerative disease related to neuroinflammation.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2018.04a
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• pp.89-89
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• 2018

Abeliophyllum distichum is a medicinal plant used in regional traditional medicine to relieve pain in inflammatory processes. In this study, anti-inflammatory effects of Abeliophyllum distichum stem (ADS) ethyl acetate extract were examined. Furthermore, possible molecular mechanisms of the anti-inflammatory effects were dissected. The anti-inflammatory activity was investigated by inhibition of lipopolysaccharide (LPS) induced pro-inflammatory cytokine production in murine macrophage-like cell line Raw264.7 cells and human microglial cell line BV2 cells. The measurement of the induced pro-inflammatory cytokine levels were carried out by ELISA. The phosphorylation of ERK1/2, JNK, and MAPK, and the nuclear expression of nuclear factor $NF-{\kappa}B$ p65 were investigated by Western blot analysis. The extract of ADS significantly decreased the production of pro-inflammatory cytokines. In addition, the extract suppressed the phosphorylation of ERK1/2, JNK, and p38 MAPK, and the nuclear translocation of $NF-{\kappa}B$ p65 in activated cells. Our findings provide evidence for the popular use of Abeliophylli distichum in inflammation around Goesan region and also suggest that the stem extract has potential therapeutic benefits against several inflammatory diseases.

• Natural Product Sciences
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• v.27 no.4
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• pp.293-299
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• 2021

The ethyl acetate fractions prepared from the leaves of Thuja orientalis significantly inhibited nitric oxide (NO) production in lipopolysaccharide-stimulated BV2 microglial cells. According to bioassay-coupled LC-QTOF MS/MS, the components near 22 and 25 mins in the mass chromatogram highly inhibited NO production and were expected to be labdane diterpenes, and the active components were characterized via further isolation. The results of the NO production inhibitory assay of the isolated compounds correlated well with the results of bioassay-coupled LC-QTOF MS/MS. Among the identified constituents, NO production inhibitory activities of 16-hydroxy-labda-8(17),13-diene-15,19-dioic acid butenolide (2) and 15-hydroxypinusolidic acid (3) were newly reported. Taken together, these results demonstrated that LC-QTOF MS/MS coupled with NO production inhibition assay was a powerful tool for accurately predicting new anti-inflammatory constituents in the extracts from natural products. Moreover, it provided a potential basis for broadening the application of bioassay-coupled LC-QTOF MS/MS in natural product research.

• The Journal of Korean Medicine
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• v.43 no.1
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• pp.99-111
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• 2022

Objectives: Rehmanniae Radix Preparata (RRP) has been used as a traditional remedy to treat gynecology and endocrine diseases. Recently, studies on antioxidant and anti-inflammatory effects of RRP have been reported, so it was judged that RRP extracts would have an anti-depressive effect. Methods: We investigated the anti-neuroinflammatory and anti-depressive effect of RRP on lipopolysaccharide (LPS)-induced depression and LPS-stimulated BV2 microglia. RRP inhibited the LPS-stimulated excessive release of nitrite in the BV2 cells. RRP also significantly inhibited the inflammatory cytokines such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-6 in LPS-stimulated BV2 microglial cells. Results: RRP significantly suppressed the LPS-induced mitogen-activated protein kinase (MAPKs) and nuclear factor (NF)-𝜅B activation. In addition, administration of RRP not only inhibited the immobility time in the forced swimming test (FST) but also increased the total travel distance in the open field test (OFT). Also, RRP inhibited the elevation of TNF-alpha, IL-1beta, and IL-6 in brain of LPS-injected mice. Conclusions: Considering the overall results, our study showed that RRP exhibited the anti-neuroinflammatory and anti-depressive activities via deactivation of MAPKs and NF-𝜅B.

• Journal of Life Science
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• v.27 no.1
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• pp.8-14
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• 2017

Died Gardenia jasminoides fruit is used as a dye in the food and clothes industries in Asia. The present study investigated the anti-inflammatory effects of aqueous extract of G. jasminoides fruits (GJ) in BV-2 microglial cells. GJ inhibited lipopolysaccharide-induced nitric oxide (NO) secretion, inducible nitric oxide synthase (iNOS) expression, and reactive oxygen species production, without affecting cell viability. Furthermore, GJ increased the expression of heme oxygenase-1 (HO-1) in a dose-dependent manner. Moreover, the inhibitory effect of GJ on iNOS expression was abrogated by small interfering RNA-mediated knock-down of HO-1. In addition, GJ induced nuclear translocation of nuclear factor E2-related factor 2 (Nrf2), a transcription factor that regulates HO-1 expression. GJ-mediated expression of HO-1 was suppressed by LY294002, a phosphoinositide 3-kinase (PI-3K) inhibitor, and SB203580, a p38 kinase inhibitor, but not by the extracellular signal-regulated kinase (ERK) inhibitor PD98059 or c-Jun N-terminal kinase (JNK) inhibitor SP600125. GJ also enhanced the phosphorylation of Akt and p38. These results suggest that GJ suppresses the production of NO, a pro-inflammatory mediator, by inducing HO-1 expression via PI-3K/Akt/p38 signaling. These findings illustrate a novel molecular mechanism by which extract from G. jasminoides fruits inhibits neuroinflammation.