• 한국수정란이식학회:학술대회논문집
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• 한국수정란이식학회 2005년도 제5회 발생공학 국제심포지엄 및 학술대회
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• pp.41-41
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• 2005

• Biomolecules & Therapeutics
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• 제21권5호
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• pp.332-337
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• 2013

Microglial activation plays an important role in the development and progression of various neurological disorders such as cerebral ischemia, multiple sclerosis, and Alzheimer's disease. Thus, controlling microglial activation can serve as a promising therapeutic strategy for such brain diseases. In the present study, we showed that kalopanaxsaponin A, a triterpenoid saponin isolated from Kalopanax pictus, inhibited inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and tumor necrosis factor (TNF)-${\alpha}$ expression in lipopolysaccharide (LPS)-stimulated microglia, while kalopanaxsaponin A increased anti-inflammatory cytokine interleukin (IL)-10 expression. Subsequent mechanistic studies revealed that kalopanaxsaponin A inhibited LPS-induced DNA binding activities of NF-${\kappa}B$ and AP-1, and the phosphorylation of JNK without affecting other MAP kinases. Furthermore, kalopanaxsaponin A inhibited the intracellular ROS production with upregulation of anti-inflammatory hemeoxygenase-1 (HO-1) expression. Based on the previous reports that JNK pathway is largely involved in iNOS and proinflammatory cytokine gene expression via modulating NF-${\kappa}B$/AP-1 and ROS, our data collectively suggest that inhibition of JNK pathway plays a key role in anti-inflammatory effects of kalopanaxsaponin A in LPS-stimulated microglia.

• 동의생리병리학회지
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• 제24권3호
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• pp.463-469
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• 2010

This research is performed to obtain positive evidences of Mori cortex, a kind of oriental medicinal herbs, in the cellular levels. The extracts of M. cortex have shown anti-inflammatory effects against cutaneous inflammation and clinical effects on pulmonary asthma and congestion in oriental medicine. Thus BV2 cells were chosen because microglia are considered as the main immunocompetent cells in the central nervous system. Lipopolysaccharide (LPS)-induced microglial activation of cultured BV2 cells and subsequent release of nitric oxide (NO) and Prostaglandin E2 (PGE2) were effectively suppressed by methylene chloride extract of Morus alba L. (MEMA). From the inflammation-mediated mRNA and protein analyses, we showed that inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-$1{\beta}$ (IL-$1{\beta}$) and tumor necrosis alpha (TNF-${\alpha}$) induced by LPS were markedly decreased by MEMA treatment. From the observation of nuclear factor-kB (NF-${\kappa}B$) which is controlling and mediating inflammation through COX-2 and iNOS, there showed that p65, a subunit of NF-${\kappa}B$, was increased in nuclear and $I{\kappa}B$, a competitor of NF-${\kappa}B$, was recovered in cytosol after MEMA treatment. These are corresponding with results of iNOS, COX-2, IL-$1{\kappa}$ and TNF-${\alpha}$, and confirm some suppressive effect against transcriptional activation of NF-${\kappa}B$. In conclusion, the anti-inflammatory action of M. cortex against BV2 microglia cells is expected to protect nerve tissues through suppression of neuronal inflammation in various neurodegenerative diseases.

• Biomolecules & Therapeutics
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• 제27권5호
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• pp.442-449
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• 2019

This study sought to evaluate the effects of Asiatic acid in LPS-induced BV2 microglia cells and 1-methyl-4-phenyl-pyridine ($MPP^+$)-induced SH-SY5Y cells, to investigate the potential anti-inflammatory mechanisms of Asiatic acid in Parkinson's disease (PD). SH-SY5Y cells were induced using $MPP^+$ to establish as an in vitro model of PD, so that the effects of Asiatic acid on dopaminergic neurons could be examined. The NLRP3 inflammasome was activated in BV2 microglia cells to explore potential mechanisms for the neuroprotective effects of Asiatic acid. We showed that Asiatic acid reduced intracellular production of mitochondrial reactive oxygen species and altered the mitochondrial membrane potential to regulate mitochondrial dysfunction, and suppressed the NLRP3 inflammasome in microglia cells. We additionally found that treatment with Asiatic acid directly improved SH-SY5Y cell viability and mitochondrial dysfunction induced by $MPP^+$. These data demonstrate that Asiatic acid both inhibits the activation of the NLRP3 inflammasome by downregulating mitochondrial reactive oxygen species directly to protect dopaminergic neurons from, and improves mitochondrial dysfunction in SH-SY5Y cells, which were established as a model of Parkinson's disease. Our finding reveals that Asiatic acid protects dopaminergic neurons from neuroinflammation by suppressing NLRP3 inflammasome activation in microglia cells as well as protecting dopaminergic neurons directly. This suggests a promising clinical use of Asiatic acid for PD therapy.

• BMB Reports
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• 제55권4호
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• pp.181-186
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• 2022

Ventriculomegaly induced by the abnormal accumulation of cerebrospinal fluid (CSF) leads to hydrocephalus, which is accompanied by neuroinflammation and mitochondrial oxidative stress. The mitochondrial stress activates mitochondrial unfolded protein response (UPRmt), which is essential for mitochondrial protein homeostasis. However, the association of inflammatory response and UPRmt in the pathogenesis of hydrocephalus is still unclear. To assess their relevance in the pathogenesis of hydrocephalus, we established a kaolin-induced hydrocephalus model in 8-week-old male C57BL/6J mice and evaluated it over time. We found that kaolin-injected mice showed prominent ventricular dilation, motor behavior defects at the 3-day, followed by the activation of microglia and UPRmt in the motor cortex at the 5-day. In addition, PARP-1/NF-κB signaling and apoptotic cell death appeared at the 5-day. Taken together, our findings demonstrate that activation of microglia and UPRmt occurs after hydrocephalic ventricular expansion and behavioral abnormalities which could be lead to apoptotic neuronal cell death, providing a new perspective on the pathogenic mechanism of hydrocephalus.

• 대한본초학회지
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• 제28권2호
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• pp.93-101
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• 2013

Objects : Baicalein is a major bioactive flavonoid component of Scutellaria baicalensis Georgi that shows a wide range of biological activities, including neuroprotections and anti-inflammatory actions. Hence it is a potential therapeutic material for the treatment of neuroinflammation. In this study, we investigated the modulatory effect of baicalein on neuroinflammation. Method : Pro-inflammatory cytokines (TNF-${\alpha}$, IL-$1{\beta}$ and IL-6 mRNA), COX-2 mRNA expression and microglial activation in the brain tissue is induced by systemic lipopolysaccharide (LPS) treatment in C57BL/6 mice. Baicalein was treated orally with 10, 20, and 30 mg/kg 1 hour prior to the LPS (3 mg/kg, i.p.) injection. TNF-${\alpha}$, IL-$1{\beta}$, IL-6 and COX-2 mRNA expression in the brain tissue was measured by the quantitative real-time polymerase chain reaction(PCR) method. Iba1 expression in the brain was measured by western blotting method. Microglia was observed with immunohistochemistry. Results : Baicalein 30 mg/kg significantly attenuated the expression of TNF-${\alpha}$, IL-$1{\beta}$, IL-6 and COX-2 mRNA in the brain tissue. Baicalein 20 mg/kg significantly attenuated the expression of IL-6 mRNA in the brain tissue. Baicalein 30 mg/kg significantly attenuated the expression of Iba1 protein expression in the brain tissue. Baicalein 30 mg/kg significantly decreased the number and cell size of microglia in the cerebral cortex and hypothalamic region and the area percentage of Iba1-expressed microglia in the hippocampus. Conclusion : These results demonstrated that baicalein attenuates LPS induced neuroinflammation in the mice via reduction of pro-inflammatory cytokines (TNF-${\alpha}$, IL-$1{\beta}$, IL-6), COX-2 mRNA expression and microglial activation.

• International Journal of Oral Biology
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• 제45권2호
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• pp.33-41
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• 2020

Neuroinflammation is known as the main mechanism implicated in the advancement of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. The main feature of neuroinflammation is associated with the activation of microglia. The activated microglia increase proinflammatory cytokine production and induce progressive neuronal cell death. Citrus flavonoids show neuroprotective effects that are associated with the anti-inflammatory action of flavonoids in neurodegenerative diseases. Among these citrus flavonoids, kaempferol, naringin, and nobiletin show inhibitory effects on nuclear factor-κB and mitogen-activated protein kinase signaling pathways that can modulate inflammatory conditions in microglial cells. In the present review, we present the anti-inflammatory activities of citrus flavonoids and therapeutic potential of flavonoids as neuroprotective agents.

• Journal of Ginseng Research
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• 제43권1호
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• pp.58-67
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• 2019

Background: Diabetic neuropathy is one of the most devastating ailments of the peripheral nervous system. Neuropathic pain develops in ~30% of diabetics. Here, we examined the suppressive effect of GS-KG9 on neuropathic pain induced by streptozotocin (STZ). Methods: Hyperglycemia was induced by intraperitoneal injection of STZ. Rats showing blood glucose level > 250 mg/dL were divided into five groups, and treatment groups received oral saline containing GS-KG9 (50 mg/kg, 150 mg/kg, or 300 mg/kg) twice daily for 4 wk. The effects of GS-KG9 on pain behavior, microglia activation in the lumbar spinal cord and ventral posterolateral (VPL) nucleus of the thalamus, and c-Fos expression in the dorsal horn of the lumbar spinal cord were examined. Results: The development of neuropathic pain began at Day 5 and peaked at Week 4 after STZ injection. Mechanical and thermal pains were both significantly attenuated in GS-KG9-treated groups from 10 d after STZ injection as compared to those in the STZ control. GS-KG9 also repressed microglia activation in L4 dorsal horn and VPL region of the thalamus. In addition, increase in c-Fos-positive cells within L4 dorsal horn lamina I and II of the STZ control group was markedly alleviated by GS-KG9. Conclusion: These results suggest that GS-KG9 effectively relieves STZ-induced neuropathic pain by inhibiting microglial activation in the spinal cord dorsal horn and VPL region of the thalamus.

• Archives of Pharmacal Research
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• 제27권3호
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• pp.314-318
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• 2004

Microglia are the major inflammatory cells in the central nervous system and become activated in response to brain injuries such as ischemia, trauma, and neurodegenerative diseases including Alzheimer's disease (AD). Moreover, activated microglia are known to release a variety of proinflammatory cytokines and oxidants such as nitric oxide (NO). Minocycline is a semi-synthetic second-generation tetracycline that exerts anti-inflammatory effects that are completely distinct form its antimicrobial action. In this study, the inhibitory effects of minocycline on NO and prostaglandin E$_2$ (PGE$_2$) release was examined in lipopolysaccharides (LPS)-challenged BV2 murine microglial cells. Further, effects of minocycline on inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression levels were also determined. The results showed that minocycline significantly inhibited NO and PGE$_2$ production and iNOS and COX-2 expression in BV2 microglial cells. These findings suggest that minocycline should be evaluated as potential therapeutic agent for various pathological conditions due to the excessive activation of microglia.

• 대한한의학회지
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• 제31권5호
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• pp.167-178
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• 2010

Objectives: The present study investigated the effects of acupuncture treatment and their mechanism by using the kainic acid (KA)-induced epilepsy mouse model. Materials and Methods: The seizure was induced by an intraperitoneal (i.p.) injection of 30 mg/kg KA, and the acupuncture treatment was subsequently administered to acupoint Shaofu(HT8) bilaterally with two pretreatment sessions before injection (total 3 times over 3 days). Twenty four hours after injection, we observed the survival of neuronal cells in the CA3 region of the hippocampus. In addition, the activation of microglia and astrocytes was observed by using CD11b and GFAP immunohistochemistry in the same region. Results: The results indicate that acupuncture treatment reduced the rate of neural cell death in the CA3 region of the hippocampus and decreased the activations of microglia and astrocytes in this region. Conclusion: These results demonstrate that acupuncture treatment protects hippocampal neuronal cell death from KA-induced epileptic seizure by inhibiting the activations of microglia and astrocytes.