• BMB Reports
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• v.46 no.8
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• pp.398-403
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• 2013

Inflammatory conditions mediated by activated microglia lead to chronic neuro-degenerative diseases such as Alzheimer's, Parkinson's, and Huntington's diseases. This study was conducted to determine the effect of floridoside isolated from marine red algae Laurencia undulata on LPS (100 ng/ml) activated inflammatory responses in BV-2 microglia cells. The results show that floridoside has the ability to suppress pro-inflammatory responses in microglia by markedly inhibiting the production of nitric oxide (NO) and reactive oxygen species (ROS). Moreover, floridoside down-regulated the protein and gene expression levels of iNOS and COX-2 by significantly blocking the phosphorylation of p38 and ERK in BV-2 cells. Collectively, these results indicate that floridoside has the potential to be developed as an active agent for the treatment of neuro-inflammation.

• BMB Reports
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• v.55 no.9
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• pp.447-452
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• 2022

Neurogenic differentiation 1 (NeuroD1) is an essential transcription factor for neuronal differentiation, maturation, and survival, and is associated with inflammation in lipopolysaccharide (LPS)-induced glial cells; however, the concrete mechanisms are still ambiguous. Therefore, we investigated whether NeuroD1-targeting miRNAs affect inflammation and neuronal apoptosis, as well as the underlying mechanism. First, we confirmed that miR-30a-5p and miR-153-3p, which target NeuroD1, reduced NeuroD1 expression in microglia and astrocytes. In LPS-induced microglia, miR-30a-5p and miR-153-3p suppressed pro-inflammatory cytokines, reactive oxygen species, the phosphorylation of c-Jun N-terminal kinase, extracellular-signal-regulated kinase (ERK), and p38, and the expression of cyclooxygenase and inducible nitric oxide synthase (iNOS) via the NF-κB pathway. Moreover, miR-30a-5p and miR-153-3p inhibited the expression of NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasomes, NLRP3, cleaved caspase-1, and IL-1β, which are involved in the innate immune response. In LPS-induced astrocytes, miR-30a-5p and miR-153-3p reduced ERK phosphorylation and iNOS expression via the STAT-3 pathway. Notably, miR-30a-5p exerted greater anti-inflammatory effects than miR-153-3p. Together, these results indicate that miR-30a-5p and miR-153-3p inhibit MAPK/NF-κB pathway in microglia as well as ERK/STAT-3 pathway in astrocytes to reduce LPS-induced neuronal apoptosis. This study highlights the importance of NeuroD1 in microglia and astrocytes neuroinflammation and suggests that it can be regulated by miR-30a-5p and miR-153-3p.

• Biomolecules & Therapeutics
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• v.29 no.5
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• pp.483-491
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• 2021

Parkinson's disease (PD) is a neurodegenerative disorder that involves the loss of dopaminergic neurons in the substantia nigra (SN). Matrix metalloproteinases-8 (MMP-8), neutrophil collagenase, is a functional player in the progressive pathology of various inflammatory disorders. In this study, we administered an MMP-8 inhibitor (MMP-8i) in Leucine-rich repeat kinase 2 (LRRK2) G2019S transgenic mice, to determine the effects of MMP-8i on PD pathology. We observed a significant increase of ionized calcium-binding adapter molecule 1 (Iba1)-positive activated microglia in the striatum of LRRK2 G2019S mice compared to normal control mice, indicating enhanced neuro-inflammatory responses. The increased number of Iba1-positive activated microglia in LRRK2 G2019S PD mice was down-regulated by systemic administration of MMP-8i. Interestingly, this LRRK2 G2019S PD mice showed significantly reduced size of cell body area of tyrosine hydroxylase (TH) positive neurons in SN region and MMP-8i significantly recovered cellular atrophy shown in PD model indicating distinct neuro-protective effects of MMP-8i. Furthermore, MMP-8i administration markedly improved behavioral abnormalities of motor balancing coordination in rota-rod test in LRRK2 G2019S mice. These data suggest that MMP-8i attenuates the pathological symptoms of PD through anti-inflammatory processes.

• Molecular & Cellular Toxicology
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• v.5 no.2
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• pp.147-152
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• 2009

This study was conducted to evaluate the inflammatory mechanisms of LPS-stimulated BV-2 microglial cells. The inflammation mechanism was evaluated in BV-2 cells with or without LPS treated using the Affymetrix microarray analysis system. The microarray analysis revealed that B cell receptor signaling pathway, cytokine-cytokine receptor interaction, Jak-STAT signaling pathway, MAPK signaling pathway, Neuro-active ligand-receptor interaction, TLR signaling path-way, and T cell receptor signaling pathway-related genes were up-regulated in LPS stimulated BV-2 cells. Selected genes were validated using real time RTPCR. These results can help an effective therapeutic approach to alleviating the progression of neuro-in-flammatory diseases.

• Journal of Korean Neurosurgical Society
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• v.52 no.5
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• pp.488-490
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• 2012

Behçet's disease (BD) is an inflammatory systemic disorder with oral and genital ulcers, as well as ophthalmologic and cutaneous symptoms. Neurological manifestations in BD represent between 2.2% to 50% of the cases. The 25-year-old male patient, diagnosed with BD three years earlier, was admitted to our clinic with complaints of recurrent headaches. Tumor-like-parenchimal involvement was detected on a cranial magnetic resonance imaging. The lesion was removed surgically and then he suffered from right hemiparesis and epilepsy. Pathological examination of the lesion noted a demyelinating non-tumoural etiology. A neuro-Beh$\check{g}$et's case with parenchymal involvement has been examined in light of the literature, in terms of a tumor and a demyelinating disease differential diagnosis.

• Investigative Magnetic Resonance Imaging
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• v.22 no.3
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• pp.187-193
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• 2018

Sweet's syndrome also known as acute neutrophilic dermatosis is a multisystem inflammatory disorder characterized by fever, malaise, leukocytosis, and skin lesions. Sweet's syndrome affects multiple organs though only rarely does it affect the central nervous system (CNS) when it does it is called Neuro-Sweet disease (NSD). We report on a case study of a biopsy-proven NSD in a 50 year old man. Serial magnetic resonance imaging (MRI) showed repeated CNS involvement of Sweet's syndrome after a respiratory tract infection preceded it. On the MRI, T2 hyperintense lesions occurred at multiple sites and disappeared after steroid therapy.

• The Journal of Korean Medicine
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• v.43 no.4
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• pp.20-32
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• 2022

Objectives: Kyungok-go (KOG) is a traditional multi-herbal medicine commonly used for enforcing weakened immunity for long time. Recently, there are several reports that KOG has anti-inflammatory and immuno-stimulatory activities in many experimental models. However, the protective effects of KOG on neuronal inflammation are still undiscovered. Thus, we investigated the neuro-protective activity of KOG on lipopolysaccharide (LPS)-stimulated mouse microglia cells. To find out KOG's anti-neuroinflammatory effects on microglial cells, we examined the production of nitrite using griess assay, and mRNA expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2 and interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α using real time RT-PCR. In addition, to examine the regulating mechanisms of KOG, we investigated the protein expression of mitogen-activated protein kinases (MAPKs) and Iκ-Bα by western blot. KOG inhibited the elevation of nitrite, iNOS and COX-2 on LPS-stimulated BV2 cells. Also, KOG significantly inhibited the pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α on LPS-stimulated BV2 microglial cells. Moreover, KOG inhibited the activation of c-Jun N-terminal kinase (JNK), P38 and degradation of Iκ-Bα but not the activation of extracellular signal regulated kinase (ERK) on LPS-stimulated BV2 microglial cells. These results showed KOG has the anti-inflammatory effects through the inhibition on nitrite, iNOS, COX-2, IL-1β, IL-6, and TNF-α via the deactivation of JNK, p38 and nuclear factor (NF)-κB on LPS-stimulated BV2 microglial cells. Thereby, KOG could offer the new and promising treatment for neurodegenerative disease related to neuroinflammation.

• Korean Journal of Pharmacognosy
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• v.52 no.4
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• pp.212-218
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• 2021

Fatsia japonica is grown wild to Eastern Asia, including Korea, Japan, and Taiwan and it is known as ornamental plant, and it is also known that pharmacological action. In this study, we have selected the stem of F. japonica with consideration about biological activities and amount of yield. In addition, four compounds (1-4) were isolated from the stem of F. japonica. Extensive spectroscopic and chemical studies established the structures of these compounds as maltose (1), begoniifolide A (2), leiyemudanoside B (3), leonticin F (4). All of the compounds were investigated for their anti-inflammatory, anti-neuroinflammatory, and neuro-protective effects on RAW264.7, BV2, and HT22 cells. However, among four compounds, there were no effects by maltose (1), begoniifolide A (2), leiyemudanoside B (3), leonticin F (4) on the anti-inflammatory, anti-neuroinflammatory, and neuro-protective action. This is the first report on the isolation of maltose (1), begoniifolide A (2), leiyemudanoside B (3), leonticin F (4) from the stem of F. japonica. Begoniifolide A (2), leiyemudanoside B (3), leonticin F (4) were isolated for the first time from this plant. It might be necessary to continue the further studies to find the biological active compounds isolated from the stem of F. japonica.

• Biomolecules & Therapeutics
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• v.27 no.1
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• pp.92-100
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• 2019

Ginger, one of worldwide consumed dietary spice, is not only famous as food supplements, but also believed to exert a variety of remarkable pharmacological activity as herbal remedies. In this study, a ginger constituent, 12-dehydrogingerdione (DHGD) was proven that has comparable anti-inflammatory activity with positive control 6-shogaol in inhibiting LPS-induced interleukin (IL)-6, tumor necrosis factor $(TNF)-{\alpha}$, prostaglandin (PG) $E_2$, nitric oxide (NO), inducible NO synthase (iNOS) and cyclooxygenase (COX)-2, without interfering with COX-1 in cultured microglial cells. Subsequent mechanistic studies indicate that 12-DHGD may inhibit neuro-inflammation through suppressing the LPS-activated $Akt/IKK/NF-{\kappa}B$ pathway. Furthermore, 12-DHGD markedly promoted the activation of NF-E2-related factor (Nrf)-2 and heme oxygenase (HO)-1, and we demonstrated that the involvement of HO-1 on the production of pro-inflammatory mediators such as NO and $TNF-{\alpha}$ by using a HO-1 inhibitor, Zinc protoporphyrin (Znpp). These results indicate that 12-DHGD may protect against neuro-inflammation by inhibiting $Akt/IKK/I{\kappa}B/NF-{\kappa}B$ pathway and promoting Nrf-2/HO-1 pathway.

• The Journal of Korean Medicine
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• v.26 no.4
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• pp.74-86
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• 2005

Background: There are increasing neuro-degenerative disorders with aging. Paeoniae Radix(PR) possesses various pharmacological effects such as sedative, analgesic, anti-inflammatory, anti-stress and neuro-protective actions. Also antiaging and anti-cancer effects of PR were reported. Our purpose was to investigate whether PR is useful on the treatment of Parkinson's disease, one of the neuro-degenerative disorders. Objective: We investigated whether Paeonia Radix possesses a protective effect against 1-methyl-4 phenylpyridine(MPP+)-induced cytotoxicity in neuronal cells. Methods: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) assay, flow cytometry, DNA fragmentation assay, reverse transcription-polymerase chain reaction(RT-PCR), and Western blotting were performed on SK-N-MC neuroblastoma cells. Results: Cells treated with MPP+ exhibited several apoptotic features, while cells pre-treated with Paeonia Radix prior to MPP+ exposure showed s decrease in the occurrence of apoptotic features. Conclusions: These results suggest that Paeonia Radix may exert a protective effect against MPP+-induced apoptosis in SK-N-MC neuroblastoma cells.