• Proceedings of the PSK Conference
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• 2003.04a
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• pp.207.1-207.1
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• 2003

Ursodeoxycholic acid (UDCA) has been known commonly improving hyperbilirubinemia and excretion abnormality of bromsulphalein, which are appeared in the liver, and reducing the release of cholesterol from bile duct. In our study, UDCA was aimed to know if the agent can inhibit the pathogenesis of AD by suppressing the microglial activation when stimulated particularly by A${\beta}$ peptide, which is known a major cause of AD. (omitted)

• Journal of Korean Neurosurgical Society
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• v.59 no.2
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• pp.98-105
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• 2016

Objective : Lumbar disc herniation can induce sciatica by mechanical compression and/or chemical irritation. The aim of this study was to compare the effects of GCSB-5 (Shinbaro$^{(R)}$) and NSAIDs on pain-related behavior and on the expressions of microglia, astrocytes, CGRP, TRPV1, IL-6, and CX3CL1 in a rat model of lumbar disc herniation. Methods : 112 male Sprague-Dawley rats underwent implantation of nucleus pulposus to a dorsal root ganglion (DRG). Rats were divided into five groups as follows; a saline group (the vehicle control group) (n=27), a 10 mg/kg aceclofenac group (the aceclofenac group) (n=22), and 100, 300 or 600 mg/kg GCSB-5 groups (the GCSB-5 100, 300, or 600 groups) (n=21 for each group). Rats were tested for mechanical allodynia at 3 days after surgery and at 1 day, 3 days, 7 days, 14 days, 21 days, 28 days, 35 days, 42 days, 49 days, and 56 days after treatment commencement. Immunohistochemical staining of microglia (Iba1), astrocytes (GFAP), CGRP, and TRPV1, and PCR for IL-6 and CX3CL1 were performed on spinal dorsal horns and DRGs at 56 days after medication commencement. Results : After 56 days of GCSB-5 300 administration, mechanical withdrawal thresholds were significantly increased (p<0.05), and immunohistochemical expressions of Iba1, GFAP, CGRP, and TRPV1 were reduced than other groups, but this difference was not statistically significant. Conclusion : These results indicate GCSB-5 reduces mechanical allodynia and downregulates neuroglial activity and the expressions of CGRP and TRPV1 in the spinal segments of a rat model of lumbar disc herniation.

• Journal of Oriental Neuropsychiatry
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• v.19 no.3
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• pp.85-100
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• 2008

Objective: This experiment was designed to investigate the effect of the KSKH hot water extract & ultra-fine powder on microglia and memory deficit model. Method: The effects of the KSKH hot water extract on expression of IL-1$\beta$, IL-6, TNF-$\alpha$ mRNA and production of IL-1$\beta$, IL-6, TNF-$\alpha$ in BV2 microglial cell line treated by lipopolysacchaide(LPS) were investigated. The effects of the KSKH hot water extract & ultra-fine-fine powder on the behavior of the memory deficit mice induced by scopolamine and AChE in serum of the memory deficit mice induced by scopolamine were investigated. Results: 1. The KSKH hot water extract suppressed the expression of IL-1$\beta$, IL-6, TNF-$\alpha$ mRNA in BV2 microglial cell line treated by LPS. 2. The KSKH hot water extract suppressed the production of IL-1$\beta$, IL-6, TNF-$\alpha$ in 100$\mu g/m\ell$ concentration of BV2 microglial cell line culture supernatant. 3. The KSKH hot water extract & ultra-fine powder decreased AChE activation significantly in the serum of the memory deficit mice induced by scopolamine. 4. The KSKH hot water extract & ultra-fine powder showed significant effect on memory impairment in the stop-through latency type of Morris water maze test. Conclusions: This experiment shows that the KSKH hot water extract & ultra-fine powder might be effective for the prevention and treatment of amnesia and Alzheimer's disease. Investigation into the clinical use of the KSKH hot water extract & ultra-fine powder for amnesia and Alzheimer's disease is suggested for future research.

• Herbal Formula Science
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• v.25 no.4
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• pp.537-551
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• 2017

Objectives : Jinnoe-san (JNS) is a novel herbal formula consisting of five oriental medicinal herbs including Polygalae Radix, Prunellae Spica, Perillae Herba, Betulae Cortex, and Lonicerae Flos. In this study, we investigated the effects and molecular mechanism of JNS on Parkinson's disease in vitro model. Methods : The effects of JNS on 1-methyl-4-phenylpyridinium ($MPP^+$)-induced cell death in SH-SY5Y cells were evaluated with a cell viability assay, flow cytometry, and western blots analysis. The effects of JNS on lipopolysaccharide (LPS)-stimulated BV2 microglia were determined with a nitric oxide (NO) assay, enzyme linked immunosorbent assays, and western blots analysis. Result : $MPP^+$-induced cell death in SH-SY5Y cells was significantly reduced by JNS pre-treatment in a dose-dependent manner. JNS inhibited the production of reactive oxygen species, mitochondria dysfunction, and apoptosis induced by $MPP^+$ in SH-SY5Y cells. Furthermore, JNS significantly activated Akt and ERK in SH-SY5Y cells and the ability of JNS to prevent mitochondria dysfunction by $MPP^+$ was antagonized by pre-treatment of LY294002 and PD98059, an Akt and ERK inhibitor, respectively. In addition, JNS inhibited LPS-induced NO and $PGE_2$ production as well as iNOS expression and secretion of TNF-${\alpha}$, pro-inflammatory cytokines without affecting the cell viability. JNS also suppressed LPS-induced ERK activation. Conclusions : These results demonstrate that JNS has a protective effect on the dopaminergic neurons against $MPP^+$-induced neurotoxicity and anti-inflammatory effect on the LPS-stimulated microglia. These findings provide evidences for JNS to be considered as a new prescription for treating Parkinson's disease.

• 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.

• The Korean Journal of Pain
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• v.37 no.2
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• pp.91-106
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• 2024

The mechanisms of the chronic pain and depression comorbidity have gained significant attention in recent years. The complement system, widely involved in central nervous system diseases and mediating non-specific immune mechanisms in the body, remains incompletely understood in its involvement in the comorbidity mechanisms of chronic pain and depression. This review aims to consolidate the findings from recent studies on the complement system in chronic pain and depression, proposing that it may serve as a promising shared therapeutic target for both conditions. Complement proteins C1q, C3, C5, as well as their cleavage products C3a and C5a, along with the associated receptors C3aR, CR3, and C5aR, are believed to have significant implications in the comorbid mechanism. The primary potential mechanisms encompass the involvement of the complement cascade C1q/C3-CR3 in the activation of microglia and synaptic pruning in the amygdala and hippocampus, the role of complement cascade C3/C3a-C3aR in the interaction between astrocytes and microglia, leading to synaptic pruning, and the C3a-C3aR axis and C5a-C5aR axis to trigger inflammation within the central nervous system. We focus on studies on the role of the complement system in the comorbid mechanisms of chronic pain and depression.

• Biomedical Science Letters
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• v.25 no.1
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• pp.92-98
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• 2019

Metformin is a drug used for the treatment of diabetes and is associated with anti-inflammatory reaction, but the underlying mechanism is unclear. In this study, we investigated the effect of metformin on the inflammatory response in BV-2 microglial cells induced by lipopolysaccharide (LPS) and S100 calcium-binding protein A8 (S100A8). The results revealed that metformin significantly attenuated several inflammatory responses in BV-2 microglial cells, including the secretion of pro-inflammatory cytokines, such as tumor necrosis factor-${\alpha}$ and interleukin (IL)-6, involved in the activation of Beclin-1, a crucial regulator of autophagy. In addition, metformin inhibited the LPS-induced phosphorylation of ERK. Metformin also suppressed the activation of NOD-like receptor pyrin domain containing 3 inflammasomes composed of NLRP3, caspase-1, and apoptosis-associated speck like protein containing a caspase recruitment domain, which are involved in the innate immune response. Notably, metformin decreased the secretion of S100A8-induced IL-6 production. These findings suggest that metformin alleviates the neuroinflammatory response via autophagy activation.

• Korean Journal of Acupuncture
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• v.30 no.1
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• pp.56-63
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• 2013

Objectives : Effects of repetitive electroacupuncture(EA) on the pain behavior and activation of spinal glial cells were examined in the rat model of neuropathic pain. Methods : Twenty one adult male Sprague-Dawley rats were randomly assigned into 3 groups(control group, SP6 group, ST36+GB34 group). Neuropathic pain was induced by tight ligation of L5 spinal nerve. Mechanical and thermal hypersensitivity of hind paw were tested. Immunohistochemistry was performed in spinal cord L5/6 of all groups. EA was treated once in a day from the $5^{th}$ day after surgery. Results : EA treatments applied to ST36 and GB34 reduced significantly both of mechanical and thermal hypersensitivity after 3 times of treatment throughout the experiments. In the SP6 group, the analgesic effect was also shown after 7 times of treatment. Immunohistochemistry demonstrated inhibition of microglia and astrocyte activation in the spinal cord L5/6 dorsal horn in the ST36+GB34 group. Conclusions : The present results suggest that repetitive EA exert strong analgesic effect on neuropathic pain. These analgesic effects in neuropathic pain are associated with suppressing the activation of microglia and astrocyte.

• Molecules and Cells
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• v.25 no.1
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• pp.99-104
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• 2008

Gangliosides, sialic acid-containing glycosphingolipids, are implicated in many neuronal diseases, but the precise molecular mechanisms underlying their pathological activities are poorly understood. Here we report that TLR2 participates in the initiation of ganglioside-triggered inflammatory signaling responses. Using FACS analysis and immunofluorescence microscopy, we found that gangliosides rapidly enhanced the cell surface expression of TLR2 in microglia, while reducing that of TLR4. The ganglioside-dependent increase of TLR2 expression was also observed at the messenger and protein levels. We also showed that gangliosides stimulate the interaction of TLR2 with Myd88, an adaptor for TLRs, and obtained evidence that lipid raft formation is closely associated with the ganglioside-induced activation of TLR2 and subsequent inflammatory signaling. These results collectively suggest that TLR2 contributes to the ability of gangliosides to cause inflammatory conditions in the brain.

• 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 $TNF-{\alpha}$.