• Journal of Environmental Science International
• /
• v.31 no.5
• /
• pp.423-429
• /
• 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.

• Proceedings of the Plant Resources Society of Korea Conference
• /
• 2018.04a
• /
• pp.92-92
• /
• 2018

Solanum nigrum L. (SNL), generally known as black nightshade, is traditionally used as medicine to reduce inflammation caused by several diseases like asthma, chronic bronchitis and liver cirrhosis. In this study, anti-inflammatory effects of SNL extract were examined and possible molecular mechanisms of the anti-inflammatory effects were investigated. The inhibitory effects of SNL extract on nitric oxide (NO), pro-inflammatory cytokines ($TNF-{\alpha}$, IL-6) and Matrix metallopeptidase 9 (MMP-9) productions were dissected using lipopolysaccharide (LPS) stimulated murine macrophage-like cell line Raw264.7 cells and human microglial cell line BV2 cells. We further investigated whether SNL extract could suppress the phosphorylation of ERK1/2, JNK, and p38 and the nuclear expression of nuclear factor $NF-{\kappa}B$ p65 in LPS-stimulated Raw264.7 cells and BV2 cells. As a result, we showed that the SNL extract significantly decreased the production of pro-inflammatory cytokines, NO, and MMP-9. In addition, the SNL strongly inhibited the phosphorylation of ERK1/2, JNK, p38 and nuclear translocation of $NF-{\kappa}B$ p65 in activated cells. We confirmed that the extracts of SNL effectively inhibits the anti-inflammatory and may be used as a therapeutic to various inflammatory diseases.

• Korean Journal of Veterinary Research
• /
• v.45 no.1
• /
• pp.7-15
• /
• 2005

To elucidate the roles of phospho-IkB expression in the development and progression of EAE, we investigated the expression of phospho-IkB in the central nervous system (CNS) of rats during experimental autoimmune encephalomyelitis (EAE) using immunohistochemistry and Western blot analysis. In Western blot analysis, the increased expression of phospho-IkB went parallel to severity of EAE. The expression of phospho-IkB increased significantly at the peak stage of EAE followed by gradual decrease. Immunohistochemical studies showed that the phospho-IkB immunoreactivity was mainly expressed in inflammatory cells (macrophages, T cells) and glial cells (astrocytes, microglial cells) at the peak stage of EAE and disappeared at the recovery stage. These findings suggest that the phosphorylation of IkB is closely associated with autoimmune inflammation in the CNS and plays an important role in the initiation and progression of EAE.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.25 no.5
• /
• pp.881-886
• /
• 2011

AMPA receptor (AMPAR)s are heterotetrameric structures made up from 4 units (GluR1-4) and are thought to underlie perception of persistent inflammatory pain. Complete Freund's adjuvant (CFA)-evoked inflammation induces synaptic GluR2 internalization, which is initiated by GluR2 phosphorylation, in dorsal horn neurons during the maintenance of CFA-induced hypersensitivity. The present study investigated whether electroacupuncture (EA) stimulation has any effect on GluR2 trafficking by using immunoblot and immunohistochemistry. We examined that CFA-induced dorsal horn GluR2 internalization was attenuated by EA treatment. EA treatment could also decrease the level of pGluR2 regardless of whether CFA injection was administrated or not. In addition, previous studies suggest that microglial cells are increased without morphological change in CFA injected animal. In our study, increases in microglial cells in CFA group were observed, whereas EA with or without CFA-injected group showed similar aspects with normal group. In conclusion, our results indicate that EA might blunt CFA-evoked inflammation by coordinating mechanisms at the upstream step of neuron activation and GluR2 phosphorylation.

• Korean Journal of Pharmacognosy
• /
• v.38 no.2 s.149
• /
• pp.170-175
• /
• 2007

Activated microglia by neuronal injury or inflammatory stimulation overproduce nitric oxide (NO) by inducible nitric oxide synthase (iNOS) and reactive oxygen species (ROS) such as superoxide anion, resulting in neurodegenerative diseases. The toxic peroxynitrite (ONOO$^-$), the reaction product of NO and superoxide anion further contributes to oxidative neurotoxicity. We tried to evaluate the effects of two kinds of varieties of Perilla frutescens var japnica Hara on the NO production in lipopolysaccharide (LPS)-activated microglia. The perilla cultivars of Namcheondeulkkae (NC) and Boradeulkkae (BR) were developed by pure line from the local variety and by a cross between 'deulkkae' and 'chajogi', respectively. Spirit, hexane, chloroform and butanol fractions of the leaves of NC and BR inhibited the production of NO in LPS-activated microglia. The fractions of BR showed stronger activity than NC and the spirit extracts was the most potent in both cultivars. The solvent fractions of BR suppressed the expression of protein and mRNA of iNOS in LPS-activated microglial cells. Moreover, the extracts of NC and BR showed the activity of peroxynitrite scavenging in cell free bioassay system. These results imply that Namcheondeulkkae and Boradeulkkae might have neuroprotective activity through the inhibition of NO production by activated microglial cells and peroxynitrite scavenging activity.

• Biomolecules & Therapeutics
• /
• v.26 no.2
• /
• pp.210-217
• /
• 2018

Neuroinflammation is an immune response within the central nervous system against various proinflammatory stimuli. Abnormal activation of this response contributes to neurodegenerative diseases such as Parkinson disease, Alzheimer's disease, and Huntington disease. Therefore, pharmacologic modulation of abnormal neuroinflammation is thought to be a promising approach to amelioration of neurodegenerative diseases. In this study, we evaluated the synthetic flavone derivative 3',4'-dihydroxyflavone, investigating its anti-neuroinflammatory activity in BV2 microglial cells and in a mouse model. In BV2 microglial cells, 3',4'-dihydroxyflavone successfully inhibited production of chemokines such as nitric oxide and prostaglandin $E_2$ and proinflammatory cytokines such as tumor necrosis factor alpha, interleukin 1 beta, and interleukin 6 in BV2 microglia. It also inhibited phosphorylation of mitogen-activated protein kinase (MAPK) and nuclear factor $(NF)-{\kappa}B$ activation. This indicates that the anti-inflammatory activities of 3',4'-dihydroxyflavone might be related to suppression of the proinflammatory MAPK and $NF-{\kappa}B$ signaling pathways. Similar anti-neuroinflammatory activities of the compound were observed in the mouse model. These findings suggest that 3',4'-dihydroxyflavone is a potential drug candidate for the treatment of microglia-related neuroinflammatory diseases.

• Journal of Acupuncture Research
• /
• v.22 no.2
• /
• pp.147-154
• /
• 2005

Objective: In this study, the effects of Liriope Platyphylla against LPS-induced inflammation was investigated. Methods: Cell viability was determined using the MTT assay. To identify expressions of COX-2 and iNOS mRNA, RT-PCR was performed. Assessment of PGE2 synthesis was performed using the PGE2 immunoassay. Measurement of NO synthesis was performed using the NO detection. Result : The MTT assay revealed that Liriope Platyphylla exerted no significant cytotoxicity in the microglial BV2 cells. RT-PCR analysis revealed that the mRNA levels of COX-2 and iNOS were significantly decreased in the LPS- and 5 mg/ml Liriope Platyphylla treated group. From the PGE2 immunoassay and NO detection, PGE2 and NO synthesis was significantly suppressed in the LPS- and 5 mg/ml Liriope Platyphylla treated group. Conclusion : In these study, Liriope Platyphylla was shown to suppress PGE2 and NO production by inhibiting LPS-stimulated enhancement of COX-2 enzyme activity and iNOS expression. It is very possible that Liriope Platyphylla can offer a valuable mode of therapy for the treatment of brain inflammatory diseases.

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

• Molecules and Cells
• /
• v.42 no.10
• /
• pp.702-710
• /
• 2019

Neuroinflammation is an important contributor to the pathogenesis of neurodegenerative disorders including Parkinson's disease (PD). We previously reported that our novel synthetic compound KMS99220 has a good pharmacokinetic profile, enters the brain, exerts neuroprotective effect, and inhibits $NF{\kappa}B$ activation. To further assess the utility of KMS99220 as a potential therapeutic agent for PD, we tested whether KMS99220 exerts an anti-inflammatory effect in vivo and examined the molecular mechanism mediating this phenomenon. In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated mice, oral administration of KMS99220 attenuated microglial activation and decreased the levels of inducible nitric oxide synthase and interleukin 1 beta ($IL-1{\beta}$) in the nigrostriatal system. In lipopolysaccharide (LPS)-challenged BV-2 microglial cells, KMS99220 suppressed the production and expression of $IL-1{\beta}$. In the activated microglia, KMS99220 reduced the phosphorylation of $I{\kappa}B$ kinase, c-Jun N-terminal kinase, and p38 MAP kinase; this effect was mediated by heme oxygenase-1 (HO-1), as both gene silencing and pharmacological inhibition of HO-1 abolished the effect of KMS99220. KMS99220 induced nuclear translocation of the transcription factor Nrf2 and expression of the Nrf2 target genes including HO-1. Together with our earlier findings, our current results show that KMS99220 may be a potential therapeutic agent for neuroinflammation-related neurodegenerative diseases such as PD.

• Biomolecules & Therapeutics
• /
• v.22 no.1
• /
• pp.17-26
• /
• 2014

${\alpha}$-Asarone exhibits a number of pharmacological actions including neuroprotective, anti-oxidative, anticonvulsive, and cognitive enhancing action. The present study investigated the effects of ${\alpha}$-asarone on pro-inflammatory cytokines mRNA, microglial activation, and neuronal damage in the hippocampus and on learning and memory deficits in systemic lipopolysaccharide (LPS)-treated C57BL/6 mice. Varying doses of ${\alpha}$-asarone was orally administered (7.5, 15, or 30 mg/kg) once a day for 3 days before the LPS (3 mg/kg) injection. ${\alpha}$-Asarone significantly reduced TNF-${\alpha}$ and IL-$1{\beta}$ mRNA at 4 and 24 hours after the LPS injection at dose of 30 mg/kg. At 24 hours after the LPS injection, the loss of CA1 neurons, the increase of TUNEL-labeled cells, and the up-regulation of BACE1 expression in the hippocampus were attenuated by 30 mg/kg of ${\alpha}$-asarone treatment. ${\alpha}$-Asarone significantly reduced Iba1 protein expression in the hippocampal tissue at a dose of 30 mg/kg. ${\alpha}$-Asarone did not reduce the number of Iba1-expressing microglia on immunohistochemistry but the average cell size and percentage areas of Iba1-expressing microglia in the hippocampus were significantly decreased by 30 mg/kg of ${\alpha}$-asarone treatment. In the Morris water maze test, ${\alpha}$-asarone significantly prolonged the swimming time spent in the target and peri-target zones. ${\alpha}$-Asarone also significantly increased the number of target heading and memory score in the Morris water maze. The results suggest that inhibition of pro-inflammatory cytokines and microglial activation in the hippocampus by ${\alpha}$-asarone may be one of the mechanisms for the ${\alpha}$-asarone-mediated ameliorating effect on memory deficits.