• Journal of Life Science
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• v.21 no.6
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• pp.796-804
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• 2011

Microglia are central nervous system (CNS)-resident professional macrophages that function as the principal immune cells responding to pathological stimulations in the CNS. Activation of microglia, induced by various pathogens, protects neurons and maintains homeostasis in the CNS, but severe activation causes inflammatory responses secreting various neurotoxic molecules such as nitric oxide (NO), prostaglandin $E_2$ ($PGE_2$) and pro-inflammatory cytokines. Allium fistulosum, a member of the onion family, is mainly cultivated for consumption, as well as medicinal use in Oriental medicine. It has been reported that A. fistulosum has various biological effects such as anti-oxidant, anti-platelet aggregation, anti-fungus and anti-cholesterol synthesis, however there has been no research about the anti-inflammatory effects of A. fistulosum extracts. In this study, it was undertaken to explore the functions of A. fistulosum as a suppressor of neuronal inflammation by using BV2 microglia cells. As a result, it was found that four kinds of extracts of A. fistulosum effectively reduced the expressions of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) at both mRNA and protein levels, and also attenuated pro-inflammatory cytokines such as tumor necrosis alpha (TNF-${\alpha}$), interleukin-$1{\beta}$ (IL-$1{\beta}$) and interleukin-6 (IL-6) at the mRNA level in BV2 stimulated by lipopolysaccharide (LPS). In addition, the extracts of A. fistulosum attenuated the release of NO markedly, as well as resulting in slight decreases of TNF-${\alpha}$ and IL-6 production, the effects of which were most significant when treated with ethyl alcohol extract from the whole A. fistulosum. In conclusion, the data indicated that the anti-inflammatory actions of A. fistulosum against BV2 microglia cells is through the down-regulation of iNOS, COX2 and pro-inflammatory cytokines such as TNF-${\alpha}$ and IL-6, and these effects are expected to help in the protection of nerve tissues by suppressions of neuronal inflammation in various neurodegenerative diseases.

• Korean Journal of Oriental Medicine
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• v.14 no.1
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• pp.145-160
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• 2008

Nelumbinis Semen(NS) has been used in traditional medicine to treat diseases such as depression and diarrhea. In inflammatory responses, microglia produces molecules which are known to play roles in the central nervous system. And we previously studied NS inhibited nitric oxide synthase and secretion of tumor necrosis factor alpha. To explore the global gene expression profiles in BV-2 microglial cell line treated with NS, microarray analysis was performed. The cells were treated with LPS or NS plus LPS for 30min, Ih, 3h, and 6h, respectively. Of 45,101 known genes, with cutoff value of 3-fold change in the expression, 340, 644, 280 and 219 genes were upregulated and 503, 570, 694 and 484 were downregulated in NS treated cells at each time point. The results of the present study shows that treatment of NS reversed the LPS-induced upregulation of such genes as Ecoxsackievirus and adenovirus receptor(CAR), pellino 1, and S100P binding protein. It is thought that microarrays will play an ever-growing role in the advance of our understanding of the pharmacologic actions NS.

• Archives of Pharmacal Research
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• v.28 no.10
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• pp.1164-1169
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• 2005

Brain microglia are phagocytic cells that are the major inflammatory response cells of the central nervous system and widely held to play important pathophysiologic roles in Alzheimer's disease (AD) in both potentially neurotoxic responses and potentially beneficial phagocytic responses. In the study, we examined whether ginsonoside Rg3, a by-product of red ginseng, enhances the microglial phagocytosis of $A{\beta}$. We found that Rg3 promoted $A{\beta}$ uptake, internalization, and digestion. Increased maximal $A{\beta}$ uptake was observed at 4 and 8 h after Rg3 pretreatment (25 ${\mu}g/mL$), and the internalized $A{\beta}$ was almost completely digested from cells within 36 h when pretreated with Rg3 comparing with single non-Rg3-treated groups. The expression of MSRA (type A MSR) was also up-regulated by Rg3 treatment in a dose- and time-dependent manner which was coincidently identified in western blots for MSRA proteins in cytosol. These results indicate that microglial phagocytosis of $A{\beta}$ may be enhanced by Rg3 and the effect of Rg3 on promoting clearance of $A{\beta}$ may be related to the MSRA-associated action of Rg3. Thus, stimulation of the MSRA might contribute to the therapeutic potentials of Rg3 in microglial phagocytosis and digestion in the treatment of AD.

• Korean Journal of Veterinary Research
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• v.46 no.3
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• pp.177-184
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• 2006

Experimental autoimmune encephalomyelitis (EAE) is a disease model of multiple sclerosis (MS) that is characterized by remittance and relapse of the disease and autoimmune and demyelinating lesions in the central nervous system (CNS). Autoimmune inflammation is maintained by secretion of a large number of protein. Previous studies have suggested that transcripts encoding osteopontin (OPN) are frequently detected in the mRNA population of MS plaques. To elucidate the functional role of OPN in initiation and development of EAE, we examined the expression and localization of OPN in the spinal cord during acute EAE. We demonstrated that OPN significantly increased at the early stage of EAE and slightly declined thereafter by western blot analysis. An immunohistochemical study revealed that OPN was constitutively expressed in some glial cells (microglia, astrocytes) of white matter and neurons in the CNS of control rats. OPN expression was shown to be increased in the same cells at the early and peak stage of EAE. To identity cells expressing OPN by double-immunofluorescence labeling, we labeled rat spinal cord sections for OPN with a monoclonal OPN antibody and with mAbs for astrocyte (GFAP), microglia/macrophage (OX42)-specific markers. The major cell types of OPN-expressing cells were activated astrocytes and microglia in the adjacent inflammatory lesions. Interestingly, OPN was mainly expressed in the end feet of astrocytes around vascular cell adhesion molecule-1 (VCAM-1) expressing endothelial cells of CNS blood vessel. These findings suggest that increased levels of OPN in activated glial cell may play an important role in the recruitment of inflammatory cells into the CNS parenchyma during EAE.

• Biomolecules & Therapeutics
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• v.23 no.3
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• pp.261-267
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• 2015

Pioglitazone (PGZ), a synthetic peroxisome proliferator-activated receptor ${\gamma}$ agonist, is known to regulate inflammatory process and to have neuroprotective effects against neurological disorders. In the present study, we examined the effects of 30 mg/kg PGZ on excitotoxic neuronal damage and glial activation in the mouse hippocampus following intracerebroventricular injection of kainic acid (KA). PGZ treatment significantly reduced seizure-like behavior. PGZ had the neuroprotective effect against KA-induced neuronal damage and attenuated the activations of astrocytes and microglia in the hippocampal CA3 region. In addition, MPO and $NF{\kappa}B$ immunoreactivities in the glial cells were also decreased in the PGZ-treated group. These results indicate that PGZ had anticonvulsant and neuroprotective effects against KA-induced excitotocix injury, and that neuroprotective effect of PGZ might be due to the attenuation of KA-induced activation in astrocytes and microglia as well as KA-induced increases in MPO and $NF{\kappa}B$.

• 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.

• Korean Journal of Pharmacognosy
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• v.38 no.2 s.149
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• pp.170-175
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• 2007

Activated microglia by neuronal injury or inflammatory stimulation overproduce nitric oxide (NO) by inducible nitric oxide synthase (iNOS) and reactive oxygen species (ROS) such as superoxide anion, resulting in neurodegenerative diseases. The toxic peroxynitrite (ONOO$^-$), the reaction product of NO and superoxide anion further contributes to oxidative neurotoxicity. We tried to evaluate the effects of two kinds of varieties of Perilla frutescens var japnica Hara on the NO production in lipopolysaccharide (LPS)-activated microglia. The perilla cultivars of Namcheondeulkkae (NC) and Boradeulkkae (BR) were developed by pure line from the local variety and by a cross between 'deulkkae' and 'chajogi', respectively. Spirit, hexane, chloroform and butanol fractions of the leaves of NC and BR inhibited the production of NO in LPS-activated microglia. The fractions of BR showed stronger activity than NC and the spirit extracts was the most potent in both cultivars. The solvent fractions of BR suppressed the expression of protein and mRNA of iNOS in LPS-activated microglial cells. Moreover, the extracts of NC and BR showed the activity of peroxynitrite scavenging in cell free bioassay system. These results imply that Namcheondeulkkae and Boradeulkkae might have neuroprotective activity through the inhibition of NO production by activated microglial cells and peroxynitrite scavenging activity.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.79.2-79.2
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• 2003

Minocycline is known to protect neurons from microglia-mediated cell death in many experimental models of brain diseases including ischemic stroke, Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), traumatic brain injury, multiple sclerosis, and Parkinson's disease. Activation of caspase-2, 3, 8, and 9 was evident within 2-8 hr following oxidative insult with 0.5 mM hydrogen peroxide in PC12 cells. Minocycline significantly attenuated activation of these caspases up to 18 hr, resulting a significant increase in cell viability as assessed by MTT assay. (omitted)

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.1
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• pp.242-245
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• 2005

The most common feature of neurodegenerative disease (i.e. Alzheimer's disease, AD) is the increased number of activated microglial cells nearby the pathogenic area of the brain, such as amyloid plaque in AD. An abnormality of protein regulation and an imbalance of clearance against ${\beta}-amyloid\;(A{\beta})$ produced amyloid precursor protein (APP) can turn microglia into the activated feature out of the ramified resting phase. We examined the possibility that ginsenoside Rb1 could attenuate the microglial activation induced by massive $A{\beta}$ that has known to induce a chronic inflammation, which is a major cause of AD by damaging neuronal cells (i.e. apoptosis or necrosis). Aggregated $A{\beta}42\;(5\;{\mu}M)$ peptide was used with lipopolysaccharide (LPS) ($10\;{\mu}g$) for a comparative control up to 48hours. We found that Rb1 reduced the production of nitric oxide as well as proinflammatory cytokines, such as $IL-1{\beta}$ and $TNF-{\alpha}$.

• The Korean Journal of Physiology and Pharmacology
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• v.4 no.5
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• pp.339-346
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• 2000

Using murine immortalized microglial cells (BV-2), we examined the regulation of RANTES production stimulated by lipopolysaccharide (LPS), focusing on the role of mitogen-activated protein kinase (MAPK) and nuclear factor $(NF)-{\kappa}B.$ The result showed that RANTES (regulated upon activation of normal T cell expressed and secreted) was induced at the mRNA and protein levels in a dose- and time-dependent manner in response to LPS. From investigations of second messenger pathways involved in regulating the secretion of RANTES, we found that LPS induced phosphorylation of extracellular signal-regulated kinase (Erk), p38 MAPK and c-Jun-N-terminal kinase (JNK), and activated $(NF)-{\kappa}B.$ To determine whether this MAPK phosphorylation is involved in LPS-stimulated RANTES production, we used specific inhibitors for p38 MAPK and Erk, SB 203580 and PD 98059, respectively. LPS-induced RANTES production was reduced approximately 80% at $25\;{\mu}M$ of SB 203580 treatment. But PD 98059 did not affect RANTES production. Pyrrolidine-dithiocarbamate (PDTC), $(NF)-{\kappa}B$ inhibitor, reduced RANTES secretion. These results suggest that LPS-induced RANTES production in microglial cells (BV-2) is mainly mediated by the coordination of p38 MAPK and $(NF)-{\kappa}B$ cascade.