• 생물정신의학
• /
• 제22권2호
• /
• pp.40-46
• /
• 2015

Neuroglial cells are fundamental for brain homeostasis and defense to intrinsic or extrinsic changes. Loss of their function and over-reactivity to stimuli contribute to the aging of brain. Alzheimer's disease (AD) could be caused by more dramatic response in neuroglia associated with various chemokines and cytokines. Neuroglia of the AD brain shares some phenotypes with aging neuroglia. In addition, neuroglial activation and neuroinflammation are commonly showed in neurodegeneration. Thus neuroglia would be a promising target for therapeutics of AD.

• 한국독성학회:학술대회논문집
• /
• 한국독성학회 2001년도 International Symposium on Dietary and Medicinal Antimutgens and Anticarcinogens
• /
• pp.7-8
• /
• 2001

A free radical is any chemical species (capable of independent existence) possessing one or more unpaired electrons, an unpaired electron being one that is alone in an orbital. Radicals (often denoted by the insertion of the radical dot (ㆍ) to indicate that one or more unpaired electrons is present) are generally less stable than non-radicals, although their reactivities vary.

• Bulletin of the Korean Chemical Society
• /
• 제34권1호
• /
• pp.271-274
• /
• 2013

• Journal of Microbiology and Biotechnology
• /
• 제28권1호
• /
• pp.12-21
• /
• 2018

Photorhabdus temperata (PT), a gram-negative bacterium, lives symbiotically within entomopathogenic nematodes. The insecticidal compounds derived from Photorhabdus are used as biopesticides in agriculture. However, the physiological properties are not well characterized. In the course of our screening for neuroprotective and anti-neuroinflammatory substances from natural products, the culture broth of PT showed considerable activities. By activity-guided purification, five anthraquinones, namely, 3-methoxychrysazine (1), 1,3-dimethoxy-8-hydroxy-9,10-anthraquinone (2), 1,3,8-trihydroxy-9,10-anthraquinone (3), 3,8-dihydroxy-1-methoxy-9,10-anthraquinone (4), and 1,3,4-trimethoxy-8-hydroxy-9,10-anthraquinone (5), were isolated from the ethyl acetate fraction of the PT culture broth. Among the isolated compounds, $75{\mu}M$ 3 significantly protected mouse hippocampal neuronal cells (HT22) against 5 mM glutamate-induced cell death via the inhibition of reactive oxygen species production, $Ca^{2+}$ influx, and lipid peroxidation. Additionally, 3 and 4 effectively suppressed the interferon-${\gamma}$-induced neuroinflammation of mouse-derived microglial cells (BV2) at 10 ng/ml, via the reduction of nitric oxide, interleukin-6, and tumor necrosis factor-${\alpha}$. Anthraquinones 3 and 4 derived from the PT culture broth are a potential starting point to discover neuroprotective and anti-neuroinflammatory drug leads. The novel compound 5 is reported for the first time in this study.

• BMB Reports
• /
• 제43권4호
• /
• pp.225-232
• /
• 2010

Parkinson's Disease (PD) is a common neurodegenerative disease characterized by the progressive degeneration of nigrostriatal dopaminergic (DA) neurons. Although the causative factors of PD remain elusive, many studies on PD animal models or humans suggest that glial activation along with neuroinflammatory processes contribute to the initiation or progression of PD. Additionally, several groups have proposed that dysfunction of the blood-brain barrier (BBB) combined with infiltration of peripheral immune cells play important roles in the degeneration of DA neurons. However, these neuroinflammatory events have only been investigated separately, and the issue of whether these phenomena are neuroprotective or neurotoxic remains controversial. We here review the current knowledge regarding the functions of these neuroinflammatory processes in the brain. Finally, we describe therapeutic strategies for the regulation of neuroinflammation with the goal of improving the symptoms of PD.

• Biomolecules & Therapeutics
• /
• 제28권2호
• /
• pp.152-162
• /
• 2020

Cerebral ischemia exhibits a multiplicity of pathophysiological mechanisms. During ischemic stroke, the reactive oxygen species (ROS) concentration rises to a peak during reperfusion, possibly underlying neuronal death. Recombinant human erythropoietin (EPO) supplementation is one method of treating neurodegenerative disease by reducing the generation of ROS. We investigated the therapeutic effect of PEGylated EPO (P-EPO) on ischemic stroke. Mice were administered P-EPO (5,000 U/kg) via intravenous injection, and middle cerebral artery occlusion (MCAO) followed by reperfusion was performed to induce in vivo ischemic stroke. P-EPO ameliorated MCAO-induced neurological deficit and reduced behavioral disorder and the infarct area. Moreover, lipid peroxidation, expression of inflammatory proteins (cyclooxygenase-2 and inducible nitric oxide synthase), and cytokine levels in blood were reduced by the P-EPO treatment. In addition, higher activation of nuclear factor kappa B (NF-κB) was found in the brain after MCAO, but NF-κB activation was reduced in the P-EPO-injected group. Treatment with the NF-κB inhibitor PS-1145 (5 mg/kg) abolished the P-EPO-induced reduction of infarct volume, neuronal death, neuroinflammation, and oxidative stress. Moreover, P-EPO was more effective than EPO (5,000 U/kg) and similar to a tissue plasminogen activator (10 mg/kg). An in vitro study revealed that P-EPO (25, 50, and 100 U/mL) treatment protected against rotenone (100 nM)-induced neuronal loss, neuroinflammation, oxidative stress, and NF-κB activity. These results indicate that the administration of P-EPO exerted neuroprotective effects on cerebral ischemia damage through anti-oxidant and anti-inflammatory properties by inhibiting NF-κB activation.

• The Korean Journal of Physiology and Pharmacology
• /
• 제22권1호
• /
• pp.63-70
• /
• 2018

Cilostazol is a selective inhibitor of type 3 phosphodiesterase (PDE3) and has been widely used as an antiplatelet agent. Cilostazol mediates this activity through effects on the cyclic adenosine monophosphate (cAMP) signaling cascade. Recently, it has attracted attention as a neuroprotective agent. However, little is known about cilostazol's effect on excitotoxicity induced neuronal cell death. Therefore, this study evaluated the neuroprotective effect of cilostazol treatment against hippocampal neuronal damage in a mouse model of kainic acid (KA)-induced neuronal loss. Cilostazol pretreatment reduced KA-induced seizure scores and hippocampal neuron death. In addition, cilostazol pretreatment increased cAMP response element-binding protein (CREB) phosphorylation and decreased neuroinflammation. These observations suggest that cilostazol may have beneficial therapeutic effects on seizure activity and other neurological diseases associated with excitotoxicity.

• 생약학회지
• /
• 제46권1호
• /
• pp.12-16
• /
• 2015

Myrrh is a resinous substance obtained from Commiphora trees, which has long been used as an antiseptic agent. A sesquiterpene, $1{\beta}$, $6{\alpha}$-dihydroxyeudesm-4(15)-ene (DE), was isolated from the hot water extract of Myrrh. In the present study, we found that DE attenuates the lipopolysaccharide (LPS)-induced inflammation in BV2 microglial cells. DE significantly inhibited LPS-induced production of pro-inflammatory mediators such as nitric oxide (NO) and prostaglandin $E_2$ ($PGE_2$) in BV2 microglia in a concentration-dependent manner without cytotoxic effect. Furthermore, DE dose-dependently suppressed the protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). These results suggest that DE may be a good candidate to regulate LPS-induced inflammatory response.

• The Korean Journal of Physiology and Pharmacology
• /
• 제25권3호
• /
• pp.217-225
• /
• 2021

Neuropathic pain (NP) that contributes to the comorbidity between pain and depression is a clinical dilemma. Neuroinflammatory responses are known to have potentially important roles in the initiation of NP and depressive mood. In this study, we aimed to investigate the effects of paeoniflorin (PF) on NP-induced depression-like behaviors by targeting the hippocampal neuroinflammation through the toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signaling pathway. We used a murine model of NP caused by unilateral sciatic nerve cuffing (Cuff). PF was injected intraperitoneally once a day for a total of 14 days. Pain and depression-like behavior changes were evaluated via behavioral tests. Pathological changes in the hippocampus of mice were observed by H&E staining. The levels of proinflammatory cytokines in the hippocampus were detected using ELISA. Activated microglia were measured by immunohistochemical staining. The TLR4/NF-κB signaling pathway-associated protein expression in the hippocampus was detected by western blotting. We found that the PF could significantly alleviate Cuff-induced hyperalgesia and depressive behaviors, lessen the pathological damage to the hippocampal cell, reduce proinflammatory cytokines levels, and inhibit microglial over-activation. Furthermore, PF downregulated the expression levels of TLR4/NF-κB signaling pathway-related proteins in the hippocampus. These results indicate that PF is an effective drug for improving the comorbidity between NP and depression.

• Biomolecules & Therapeutics
• /
• 제29권2호
• /
• pp.127-134
• /
• 2021

Neuroinflammation―a common pathological feature of neurodegenerative disorders such as Alzheimer's disease―is mediated by microglial activation. Thus, inhibiting microglial activation is vital for treating various neurological disorders. 7,3',4'-Trihydroxyisoflavone (THIF)―a secondary metabolite of the soybean compound daidzein―possesses antioxidant and anticancer properties. However, the effects of 7,3',4'-THIF on microglial activation have not been explored. In this study, antineuroinflammatory effects of 7,3',4'-THIF in lipopolysaccharide (LPS)-stimulated BV2 microglial cells were examined. 7,3',4'-THIF significantly suppressed the production of the proinflammatory mediators nitric oxide (NO), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) as well as of the proinflammatory cytokine interleukin-6 (IL-6) in LPS-stimulated BV2 microglial cells. Moreover, 7,3',4'-THIF markedly inhibited reactive oxygen species (ROS) generation. Western blotting revealed that 7,3',4'-THIF diminished LPS-induced phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), glycogen synthase kinase-3β (GSK-3β), and nuclear factor kappa B (NF-κB). Overall, 7,3',4'-THIF exerts antineuroinflammatory effects against LPS-induced microglial activation by suppressing mitogen-activated protein kinase (MAPK) and NF-κB signaling, ultimately reducing proinflammatory responses. Therefore, these antineuroinflammatory effects of 7,3',4'-THIF suggest its potential as a therapeutic agent for neurodegenerative disorders.