• 한국약용작물학회지
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• 제25권5호
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• pp.315-321
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• 2017

Background: Glycyrrhiza uralensis Radix (GR) is a crude drugs used in Asian countries that has been reported to prevent the progression of neurodegenerative diseases such as Alzheimer's disease. The present study examined whether GR and its active compounds, glycyrrhizic acid (GA) and isoliquiritigenin (IL), exerted protective effects on $H_2O_2$-induced oxidative damage in C6 glial cells. Methods and Results: We exposed C6 glial cells to hydrogen peroxide ($H_2O_2$) for 24 h and investigated the cellular response to GR and its active compounds by evaluating cell viability, reactivie oxygen species (ROS) production, and apoptosis-related protein expression. GR successfully mitigated the reduced cell viability and ROS production induced by $H_2O_2$ in C6 glial cells, IL and GA significantly increased the cell viability and decreased ROS production. In addition, IL and GA down-regulated apoptotic Baxdependent caspase-3 activation, but each compound exerted different mechanisms, i.e., IL dose-dependently decreased ROS production and, GA up-regulated anti-apoptotic Bcl-2 expression. Conclusions: These results demonstrated that GR and its active components, IL and GA, exhibit potential for use as natural neurodegenerative agents for the modulation of apoptosis in C6 glial cells.

• The Korean Journal of Physiology and Pharmacology
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• 제28권1호
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• pp.93-103
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• 2024

Satellite glial cells (SGCs), a major type of glial cell in the autonomic ganglia, closely envelop the cell body and even the synaptic regions of a single neuron with a very narrow gap. This structurally unique organization suggests that autonomic neurons and SGCs may communicate reciprocally. Glial Ca²⁺ signaling is critical for controlling neural activity. Here, for the first time we identified the machinery of store-operated Ca²⁺ entry (SOCE) which is critical for cellular Ca²⁺ homeostasis in rat sympathetic ganglia under normal and pathological states. Quantitative realtime PCR and immunostaining analyses showed that Orai1 and stromal interaction molecules 1 (STIM1) proteins are the primary components of SOCE machinery in the sympathetic ganglia. When the internal Ca²⁺ stores were depleted in the absence of extracellular Ca²⁺, the number of plasmalemmal Orai1 puncta was increased in neurons and SGCs, suggesting activation of the Ca²⁺ entry channels. Intracellular Ca²⁺ imaging revealed that SOCE was present in SGCs and neurons; however, the magnitude of SOCE was much larger in the SGCs than in the neurons. The SOCE was significantly suppressed by GSK7975A, a selective Orai1 blocker, and Pyr6, a SOCE blocker. Lipopolysaccharide (LPS) upregulated the glial fibrillary acidic protein and Toll-like receptor 4 in the sympathetic ganglia. Importantly, LPS attenuated SOCE via downregulating Orai1 and STIM1 expression. In conclusion, sympathetic SGCs functionally express the SOCE machinery, which is indispensable for intracellular Ca²⁺ signaling. The SOCE is highly susceptible to inflammation, which may affect sympathetic neuronal activity and thereby autonomic output.

• Korean Journal of Acupuncture
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• 제30권1호
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• pp.56-63
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• 2013

목적 : 신경병증성 통증 쥐 모델에서 통증 행동과 척수 교세포의 활성화에 대한 반복적 전침의 영향을 실험하였다. 방법 : 21마리 Sprague-Dawley 성체 수컷 쥐를 무작위적으로 대조군, SP6 군, ST36+GB34 군으로 나누었다. 신경병증성 통증은 L5 척수신경을 단단하게 묶는 것으로 유도하였다. 신경병증성 통증이 유도된 뒷발에 기계적 및 열적 민감도를 조사하였다. 모든 군의 L5/6 척수에서 면역조직화학염색법을 수행하였다. 수술 이후 5일째부터 하루에 한번씩 전침을 시행하였다. 결과 : 족삼리(ST36)와 양릉천(GB34)에 적용된 전침은 3번의 처치 이후 실험기간 내내 기계적 및 열적 민감도를 모두 감소시켰다. 삼음교(SP6) 군에서는 진통 효과가 7번의 처치 이후 감소됨을 보였다. 면역조직화학염색법은 ST36+GB34 군에서 L5/6 척수 후각에서 교세포와 성상세포의 활성화가 억제됨을 보였다. 결론 : 이 결과는 반복적인 전침은 신경병증성 통증에 강한 진통 효과를 발휘 하는 것을 시사한다. 신경병증성 통증에서 이 진통 효과는 교세포와 성상세포의 활성화를 억제하는 것과 관련이 있다.

• Biomolecules & Therapeutics
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• 제23권3호
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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 $NF{\kappa}B$.

• 한국환경과학회지
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• 제31권5호
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• pp.423-429
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• 2022

Parkinson's Disease (PD) is a chronic neurodegenerative disorder caused by the progressive loss of dopaminergic neurons, leading to decreased dopamine levels in the midbrain. Although the specific etiology of PD is not yet known, oxidative stress, inflammation, and subsequent apoptosis have been proposed to be closely related to PD pathophysiology. Cera Flava (CF) is a natural extract obtained from beehives and is isolated through the heating, compression, filtration, and purification of beehives. CF has been used in traditional medicines for its various clinical and pharmacological effects. However, its effects on neurodegenerative diseases are unknown. Therefore, we investigated the effects of CF against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD in mice and explored the underlying mechanism of action. In MPTP-induced PC12 cells, CF protected NADH dehydrogenase activity and inhibited lactate dehydrogenase. In the mouse model, CF promoted recovery from movement impairments, prevented dopamine depletion, and protected against MPTP-induced dopaminergic neuronal degradation. Moreover, CF downregulated glial and microglial activation. Taken together, our results suggest that CF improves behavioral impairments and protects against dopamine depletion in MPTP-induced toxicity by inhibiting glial and microglial activation.

• 동의생리병리학회지
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• 제23권2호
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• pp.374-380
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• 2009

Samryungbaikchul-san(SRBCS) has been used in oriental medicine for the treatments of gastrointestinal and neurological disorders. Here, potential protective function of SRBCS was investigated in neural tissues in Alzheimer's disease(AD) mouse model. In primary cultured cells from the spinal cord of newborn rats, treatment of ${\beta}$-amyloid peptide elevated cell counts positive to glial fibrillary acidic protein(GFAP) or caspase 3 immunoreactivity, but the co-treatment of SRBCS reduced positive cell counts. In vivo administration of scopolamine, an inhibitor of muscarinic receptor, resulted in increases in the number of glial fibrillary acidic protein(GFAP) and caspase 3-positive cells in hippocampal subfields, which was then decreased by the treatment of SRBCS or acetylcholinesterase inhibitor galathamine. The present data suggest that SRBCS may play a protective role in damaged neural tissues caused by scopolamine treatments in mice.

• Nutrition Research and Practice
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• 제11권5호
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• pp.381-387
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• 2017

BACKGROUND/OBJECTIVES: Vascular dementia (VaD) caused by reduced blood supply to the brain manifests as white matter lesions accompanying demyelination and glial activation. We previously showed that arabinoxylan consisting of arabinose and xylose, and arabinose itself attenuated white matter injury in a rat model of VaD. Here, we investigated whether larch arabinogalactan (LAG) consisting of arabinose and galactose could also reduce white matter injury. MATERIALS/METHODS: We used a rat model of bilateral common carotid artery occlusion (BCCAO), in which the bilateral common carotid arteries were exposed and ligated permanently with silk sutures. The rats were fed a modified AIN-93G diet supplemented with LAG (100 mg/kg/day) for 5 days before and 4 weeks after being subjected to BCCAO. Four weeks after BCCAO, the pupillary light reflex (PLR) was measured to assess functional consequences of injury in the corpus callosum (cc). Additionally, Luxol fast blue staining and immunohistochemical staining were conducted to assess white matter injury, and astrocytic and microglial activation, respectively. RESULTS: We showed that white matter injury in the the cc and optic tract (opt) was attenuated in rats fed diet supplemented with LAG. Functional consequences of injury reduction in the opt manifested as improved PLR. Overall, these findings indicate that LAG intake protects against white matter injury through inhibition of glial activation. CONCLUSIONS: The results of this study support our hypothesis that cell wall polysaccharides consisting of arabinose are effective at protecting white matter injury, regardless of their origin. Moreover, LAG has the potential for development as a functional food to prevent vascular dementia.

• 대한한방내과학회지
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• 제34권2호
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• pp.178-191
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• 2013

Objectives : In this study, we made an effort to investigate the protective mechanism of Ukgan-san (UGS) extracts on hypoxia-induced C6 glial cell death. Methods : The cell viability was assessed by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MMT) assay and cell morphological changes were analysed with microscope after staining with crystal violet (CV). Reactive oxygen species (ROS) formation was assessed by flow cytometer after staining with 2'7'-dichlorofluorescein diacetate (DCF-DA). We also analyzed expression of hypoxia-inducible factor-1 alpha (HIF-$1{\alpha}$) and p53, processing of procaspase-3 and procyclic acidic repetitive protein (PARP) by western blot method. Results : We estimated the elevated cell viability by UGS extract on $CoCl_2$-induced C6 glial cells. UGS attenuated $CoCl_2$-induced ROS formation in C6 glial cells and also showed a protective activity compared to antioxidants and exhibited abrogation of LDH-released by $CoCl_2$. UGS suppressed the typical apoptotic cell death markers, caspase-3 and PARP activation. UGS inhibited $CoCl_2$-induced HIF-1${\alpha}$ expression which is known as a major regulator for hypoxia-induced cell death, and suppressed p53 expression. Conclusions : These results suggest that UGS extract contains protective constituents for hypoxia-induced C6 glial cell death.

• Molecules and Cells
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• 제19권3호
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• pp.375-381
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• 2005

Phospholipase C-${\beta}$ (PLC-${\beta}$) hydrolyses phosphatidylinositol 4,5-bisphosphate and generates inositol 1,4,5-trisphosphate in response to activation of various G protein-coupled receptors (GPCRs). Using glial cells from knock-out mice lacking either PLC-${\beta}1$ [PLC-${\beta}1$ (-/-)] or PLC-${\beta}3$ [PLC-${\beta}3$ (-/-)], we examined which isotype of PLC-${\beta}$ participated in the cellular signaling events triggered by thrombin. Generation of inositol phosphates (IPs) was enhanced by thrombin in PLC-${\beta}1$ (-/-) cells, but was negligible in PLC-${\beta}3$ (-/-) cells. Expression of PLC-${\beta}3$ in PLC-${\beta}3$ (-/-) cells resulted in an increase in pertussis toxin (PTx)-sensitive IPs in response to thrombin as well as to PAR1-specific peptide, while expression of PLC-${\beta}1$ in PLC-${\beta}1$ (-/-) cells did not have any effect on IP generation. The thrombin-induced $[Ca^{2+}]_i$ increase was delayed and attenuated in PLC-${\beta}3$ (-/-) cells, but normal in PLC-${\beta}1$ (-/-) cells. Pertussis toxin evoked a delayed $[Ca^{2+}]_i$ increase in PLC-${\beta}3$ (-/-) cells as well as in PLC-${\beta}1$ (-/-) cells. These results suggest that activation of PLC-${\beta}3$ by pertussis toxin-sensitive G proteins is responsible for the transient $[Ca^{2+}]_i$ increase in response to thrombin, whereas the delayed $[Ca^{2+}]_i$ increase may be due to activation of some other PLC, such as PLC-${\beta}4$, acting via PTx-insensitive G proteins.

• 약학회지
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• 제44권5호
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• pp.448-454
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• 2000

Microglia, brain resident macrophages, play a central role in the inflammatory responses of the brain and are activated in brain injuries and several neurodegenerative diseases such as Alzheimer's and Parkinson's disease, thereby aggravating the course of these diseases. In this study, the effects of plantderived compounds such as curcumin or gingerol on the microglial activation were examined. Microglial cultures were prepared from 2~3 week mixed primary glial cultures obtained from the cerebral cortex of 1~2 day old rats and identified by immunocytochemistry using microglial-specific antibody OX-42. Microglia were activated by lipopolysaccharide (LPS) and interferon-${\gamma}$ (IFN-${\gamma}$) and the effect of curcumin or 6-gingerol on the microglial activation was examined. Specific parameters measured to monitor microglial activation were nitric oxide (NO), prostaglandin E$_2$(PGE$_2$) and tumor necrosis factor-$\alpha$ (TNF-$\alpha$) release. Curcumin (1~10 $\mu$M) inhibited NO release induced by LPS and IFN-${\gamma}$ in a dose-dependent manner whereas 6-gingerol (2~20 $\mu$M) did not have any effect on LPS/IFN-${\gamma}$-induced NO release. The levels of PGE$_2$and TNF-$\alpha$ induced by LPS and IFN-${\gamma}$ were also inhibited by 1~10 $\mu$M curcumin in a dose-dependent manner. These results showed that curcumin could modulate microglial activation.