• Journal of Environmental Science International
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• v.32 no.4
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• pp.259-266
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• 2023

Today, environmental pollution has been found to be one of the causes of various diseases, including brain and nervous system diseases. In particular, neurodegenerative diseases have been found to be caused by hyperactivation of immune system cells such as microglia. Preventive and therapeutic measures are needed to suppress them. Hirudo is known as a traditional herbal medicine, based on its multiple biological activities such as anti-eczema and anti-coagulation. In the present study, the anti-neuroinflammatory potential of hirudo extract was investigated in lipopolysccharide (LPS)-stimulated BV2 microglial cells and in mice. Hirudo extract significantly inhibited LPS-stimulated nitric oxide (NO) production and cytokine (IL-1Ra, KC, MCP-5, and RANTES) expression in a dose-dependent manner without causing cytotoxicity. Pretreatment with hirudo extract suppressed LPS-induced NF-κB p65 nuclear translocation. Moreover, hirudo extract reduced LPS-stimulated microglial acitivation and improved memory impairments. The results demonstrated that hirudo extract exerts anti-neuroinflammation activities, partly through inhibition of the NF-κB signaling pathway. These findings suggest that hirudo extract might have therapeutic potential with respect to neuroinflammation and neurodegenerative diseases.

• BMB Reports
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• v.53 no.10
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• pp.491-499
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• 2020

The extracellular matrix is a critical component of every human tissue. ECM not only functions as a structural component but also regulates a variety of cellular processes such as cell migration, differentiation, proliferation, and cell death. In addition, current studies suggest that ECM is critical for the pathophysiology of various human diseases. ECM is composed of diverse components including several proteins and polysaccharide chains such as chondroitin sulfate, heparan sulfate, and hyaluronic acid. Each component of ECM exerts its own functions in cellular and pathophysiological processes. One of the interesting recent findings is that ECM is involved in inflammatory responses in various human tissues. In this review, we summarized the known functions of ECM in neuroinflammation after acute injury and chronic inflammatory diseases of the central nerve systems.

• Journal of Ginseng Research
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• v.35 no.1
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• pp.80-85
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• 2011

Ginseng, a traditional medicine in Asian countries, is known to prevent various neuropathologic diseases such as Alzheimer's. Ginseng total saponins (GTS) in particular are one of the most effective ginseng extract compounds for neuroprotection. However, their protective effects on astrocytes are rarely reported. In pathological circumstances, astroglial activation plays a pivotal role in neuroinflammation. Subsequently, neuroinflammation induced by activated astrocytes causes brain damage. The purpose of the present study was to determine the suppressive effects of GTS on astroglial activation in lipopolysaccharide (LPS)-stimulated rat primary astrocytes. Astrocytes treated for 24 h with LPS demonstrated suppressed glialfibrillary acidic protein expression in a dose-dependent manner in the presence of GTS. GTS reduced production of proinflammatory cytokines such as tumor necrosis factor-${\alpha}$ and interleukin-1${\beta}$ and inhibited the level of inducible nitric oxide synthase, and cyclooxygenase-2 in LPS-stimulated astrocytes. Furthermore, GTS suppressed intracellular reactive oxygen species production. These modulations due to GTS may indicate neuroprotective antiinfl ammatory properties which may in turn be related to improvements in neurological performance.

• The Korean Journal of Physiology and Pharmacology
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• v.26 no.6
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• pp.415-425
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• 2022

Memory formation in the hippocampus is formed and maintained by circadian clock genes during sleep. Sleep deprivation (SD) can lead to memory impairment and neuroinflammation, and there remains no effective pharmacological treatment for these effects. Myricetin (MYR) is a common natural flavonoid that has various pharmacological activities. In this study, we investigated the effects of MYR on memory impairment, neuroinflammation, and neurotrophic factors in sleep-deprived rats. We analyzed SD-induced cognitive and spatial memory, as well as pro-inflammatory cytokine levels during SD. SD model rats were intraperitoneally injected with 10 and 20 mg/kg/day MYR for 14 days. MYR administration significantly ameliorated SD-induced cognitive and spatial memory deficits; it also attenuated the SD-induced inflammatory response associated with nuclear factor kappa B activation in the hippocampus. In addition, MYR enhanced the mRNA expression of brain-derived neurotropic factor (BDNF) in the hippocampus. Our results showed that MYR improved memory impairment by means of anti-inflammatory activity and appropriate regulation of BDNF expression. Our findings suggest that MYR is a potential functional ingredient that protects cognitive function from SD.

• International Journal of Oral Biology
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• v.45 no.2
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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 Lipid and Atherosclerosis
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• v.8 no.1
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• pp.1-7
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• 2019

Vascular dementia is the most common neuropsychiatric syndrome and is characterized by synaptic dysfunction, neuroinflammation, and cognitive dysfunction. Vascular dementia is associated with various environmental, genetic, and lifestyle risk factors. Recent research has focused on the association between vascular dementia and dietary patterns, suggesting that dietary regulation leads to better control of energy metabolism, improvements in brain insulin resistance, and the suppression of neuroinflammation. Intermittent fasting is a calorie-restriction method known to be more effective in promoting fat loss and regulating the impairment of glucose metabolism as compared with other dietary restriction regimens. Herein, the authors review the effects of intermittent fasting with regard to vascular dementia based on recent evidence and propose that intermittent fasting could be a therapeutic approach for ameliorating vascular dementia pathology and preventing its onset.

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2001.10b
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• pp.7-8
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• 2001

• Nutrition Research and Practice
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• v.14 no.6
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• pp.593-605
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• 2020

BACKGROUND/OBJECTIVES: Alzheimer's disease is common age-related neurodegenerative condition characterized by amyloid beta (Aβ) accumulation that leads cognitive impairment. In the present study, we investigated the protective effect of paeoniflorin (PF) against Aβ-induced neuroinflammation and the underlying mechanism in C6 glial cells. MATERIALS/METHODS: C6 glial cells were treated with PF and Aβ_25-35, and cell viability, nitric oxide (NO) production, and pro-inflammatory cytokine release were measured. Furthermore, the mechanism underlying the effect of PF on inflammatory responses and Aβ degradation was determined by Western blot. RESULTS: Aβ_25-35 significantly reduced cell viability, but this reduction was prevented by the pretreatment with PF. In addition, PF significantly inhibited Aβ_25-35-induced NO production in C6 glial cells. The secretion of interleukin (IL)-6, IL-1β, and tumor necrosis factor-alpha was also significantly reduced by PF. Further mechanistic studies indicated that PF suppressed the production of these pro-inflammatory cytokines by regulating the nuclear factor-kappa B (NF-κB) pathway. The protein levels of inducible NO synthase and cyclooxygenase-2 were downregulated and phosphorylation of NF-κB was blocked by PF. However, PF elevated the protein expression of inhibitor kappa B-alpha and those of Aβ degrading enzymes, insulin degrading enzyme and neprilysin. CONCLUSIONS: These findings indicate that PF exerts protective effects against Aβ-mediated neuroinflammation by inhibiting NF-κB signaling, and these effects were associated with the enhanced activity of Aβ degradation enzymes.

• The Korean Journal of Physiology and Pharmacology
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• v.24 no.1
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• pp.27-37
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• 2020

Neuroinflammation is an important process underlying a wide variety of neurodegenerative diseases. Carvacrol (CAR) is a phenolic monoterpene commonly used as a food additive due to its antibacterial properties, but it has also been shown to exhibit strong antioxidative, anti-inflammatory, and neuroprotective effects. Here, we sought to investigate the effects of CAR on inflammation in the hippocampus and prefrontal cortex, as well as the molecular mechanisms underlying these effects. In our study, lipopolysaccharide was injected into the lateral ventricle of rats to induce memory impairment and neuroinflammation. Daily administration of CAR (25, 50, and 100 mg/kg) for 21 days improved recognition, discrimination, and memory impairments relative to untreated controls. CAR administration significantly attenuated expression of several inflammatory factors in the brain, including interleukin-1β, tumor necrosis factor-α, and cyclooxygenase-2. In addition, CAR significantly increased expression of brain-derived neurotrophic factor (BDNF) mRNA, and decreased expression of Toll-like receptor 4 (TLR4) mRNA. Taken together, these results show that CAR can improve memory impairment caused by neuroinflammation. This cognitive enhancement is due to the anti-inflammatory effects of CAR medicated by its regulation of BDNF and TLR4. Thus, CAR has significant potential as an inhibitor of memory degeneration in neurodegenerative diseases.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.1
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• pp.41-51
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• 2016

Adult hippocampal dentate granule neurons are generated from neural stem cells (NSCs) in the mammalian brain, and the fate specification of adult NSCs is precisely controlled by the local niches and environment, such as the subventricular zone (SVZ), dentate gyrus (DG), and Toll-like receptors (TLRs). Epigallocatechin-3-gallate (EGCG) is the main polyphenolic flavonoid in green tea that has neuroprotective activities, but there is no clear understanding of the role of EGCG in adult neurogenesis in the DG after neuroinflammation. Here, we investigate the effect and the mechanism of EGCG on adult neurogenesis impaired by lipopolysaccharides (LPS). LPS-induced neuroinflammation inhibited adult neurogenesis by suppressing the proliferation and differentiation of neural stem cells in the DG, which was indicated by the decreased number of Bromodeoxyuridine (BrdU)-, Doublecortin (DCX)- and Neuronal Nuclei (NeuN)-positive cells. In addition, microglia were recruited with activating TLR4-NF-${\kappa}B$ signaling in the adult hippocampus by LPS injection. Treating LPS-injured mice with EGCG restored the proliferation and differentiation of NSCs in the DG, which were decreased by LPS, and EGCG treatment also ameliorated the apoptosis of NSCs. Moreover, pro-inflammatory cytokine production induced by LPS was attenuated by EGCG treatment through modulating the TLR4-NF-${\kappa}B$ pathway. These results illustrate that EGCG has a beneficial effect on impaired adult neurogenesis caused by LPS-induced neuroinflammation, and it may be applicable as a therapeutic agent against neurodegenerative disorders caused by inflammation.