The Function of NF-Kappa B During Epilepsy, a Potential Therapeutic Target

Cai, Mengtan; Lin, Weihong

doi:10.3389/fnins.2022.851394

Cited by 22 publications

(17 citation statements)

References 161 publications

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“…Moreover, our results showed that eugenol treatment suppressed the activation of NF-κB pathway, which has been considered a prototypical pro-inflammatory signaling pathway in the expression of several inflammatory cytokines, including TNFα and IL-1β. 40,41 These findings suggest that eugenol plays a neuroprotective role in SE-induced neuronal damage by alleviating reactive gliosis and enhancing the anti-inflammatory capacity.…”

Section: Discussionmentioning

confidence: 88%

Eugenol alleviates neuronal damage via inhibiting inflammatory process against pilocarpine-induced status epilepticus

Zhu

Park

Kim

et al. 2023

Exp Biol Med (Maywood)

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Neuroinflammation is one of the most common pathological outcomes in various neurological diseases. A growing body of evidence suggests that neuroinflammation plays a pivotal role in the pathogenesis of epileptic seizures. Eugenol is the major phytoconstituent of essential oils extracted from several plants and possesses protective and anticonvulsant properties. However, it remains unclear whether eugenol exerts an anti-inflammatory effect to protect against severe neuronal damage induced by epileptic seizures. In this study, we investigated the anti-inflammatory action of eugenol in an experimental epilepsy model of pilocarpine-induced status epilepticus (SE). To examine the protective effect of eugenol via anti-inflammatory mechanisms, eugenol (200 mg/kg) was administrated daily for three days after pilocarpine-induced SE onset. The anti-inflammatory action of eugenol was evaluated by examining the expression of reactive gliosis, pro-inflammatory cytokines, nuclear factor-κB (NF-κB), and the nucleotide-binding domain leucine-rich repeat with a pyrin-domain containing 3 (NLRP3) inflammasome. Our results showed that eugenol reduced SE-induced apoptotic neuronal cell death, mitigated the activation of astrocytes and microglia, and attenuated the expression of interleukin-1β and tumor necrosis factor α in the hippocampus after SE onset. Furthermore, eugenol inhibited NF-κB activation and the formation of the NLRP3 inflammasome in the hippocampus after SE. These results suggest that eugenol is a potential phytoconstituent that suppresses the neuroinflammatory processes induced by epileptic seizures. Therefore, these findings provide evidence that eugenol has therapeutic potential for epileptic seizures.

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Section: Discussionmentioning

confidence: 88%

Eugenol alleviates neuronal damage via inhibiting inflammatory process against pilocarpine-induced status epilepticus

Zhu

Park

Kim

et al. 2023

Exp Biol Med (Maywood)

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“…In epilepsy, activation of the NF‐κB pathway is upregulated in neurons, glial cells, and endothelial cells due to neuronal loss, glial cell proliferation, and blood–brain barrier dysfunction (Cai & Lin, 2022). As inflammation is one of the key features of epilepsy, seizures could induce the release of inflammatory factors, which could activate the NF‐κB pathway, and this activated NF‐κB signaling promotes their transcription to lead to inflammatory processes (Vezzani et al, 2008; Wang & Chen, 2018).…”

Section: Discussionmentioning

confidence: 99%

“…In epilepsy, activation of the NF-κB pathway is upregulated in neurons, glial cells, and endothelial cells due to neuronal loss, glial cell proliferation, and blood-brain barrier dysfunction (Cai & Lin, 2022).…”

Section: Sirt3 Deficiency Increased Se-induced Inflammatory Responsementioning

confidence: 99%

Sirtuin 3 regulates astrocyte activation by reducing Notch1 signaling after status epilepticus

Zhu,

Park,

Kim

et al. 2024

Glia

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Sirtuin3 (Sirt3) is a nicotinamide adenine dinucleotide enzyme that contributes to aging, cancer, and neurodegenerative diseases. Recent studies have reported that Sirt3 exerts anti‐inflammatory effects in several neuropathophysiological disorders. As epilepsy is a common neurological disease, in the present study, we investigated the role of Sirt3 in astrocyte activation and inflammatory processes after epileptic seizures. We found the elevated expression of Sirt3 within reactive astrocytes as well as in the surrounding cells in the hippocampus of patients with temporal lobe epilepsy and a mouse model of pilocarpine‐induced status epilepticus (SE). The upregulation of Sirt3 by treatment with adjudin, a potential Sirt3 activator, alleviated SE‐induced astrocyte activation; whereas, Sirt3 deficiency exacerbated astrocyte activation in the hippocampus after SE. In addition, our results showed that Sirt3 upregulation attenuated the activation of Notch1 signaling, nuclear factor kappa B (NF‐κB) activity, and the production of interleukin‐1β (IL1β) in the hippocampus after SE. By contrast, Sirt3 deficiency enhanced the activity of Notch1/NF‐κB signaling and the production of IL1β. These findings suggest that Sirt3 regulates astrocyte activation by affecting the Notch1/NF‐κB signaling pathway, which contributes to the inflammatory response after SE. Therefore, therapies targeting Sirt3 may be a worthy direction for limiting inflammatory responses following epileptic brain injury.

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“…Epileptogenesis is a complex pathological process involving mainly inflammatory responses and neuronal death [ 42 ]. The NF- κ B pathway is associated with inflammation and oxidative stress, plays a key role in epileptogenesis, and can regulate neuronal survival and apoptosis [ 43 ]. The IL-17 signaling pathway and TNF signaling pathway play a critical role in inducing blood-brain barrier disruption and CNS autoinflammation, which are closely associated with seizures [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

Network Pharmacology and Molecular Docking to Explore the Mechanism of Kangxian Decoction for Epilepsy

Wang

Zhang

Yang

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Purpose. Kangxian decoction (KXD) has been used in clinical practice to treat epilepsy. The purpose of this study was to explore the active components of KXD and clarify its antiepileptic mechanism through network pharmacology and molecular docking. Methods. The components of KXD were collected from the Encyclopedia of Traditional Chinese Medicine (ETCM) database and the literature was searched. Then, active ingredients were screened by SwissADME and potential targets were predicted by the SwissTargetPrediction database. Epilepsy-related differentially expressed genes were downloaded from the Gene Expression Omnibus database. A component-target-pathway network was constructed with Cytoscape. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and protein‒protein interaction network analysis revealed the potential mechanism and critical targets. Receiver operating characteristic (ROC) curves and box plots in microarray data validated the good diagnostic value and significant differential expression of these critical genes. Molecular docking verified the association between active ingredients and essential target proteins. Results. In our study, we screened the important compounds of KXD for epilepsy, including quercetin, baicalin, kaempferol, yohimbine, geissoschizine methyl ether, baicalein, etc. KXD may exert its therapeutic effect on epilepsy through the following targets: PTGS2, MMP9, CXCL8, ERBB2, and ARG1, acting on the following pathways: neuroactive ligand-receptor interactions, arachidonic acid metabolism, IL-17, TNF, NF-kappa B, and MAPK signaling pathways. The molecular docking results showed that the active ingredients in KXD exhibited good binding ability to the key targets. Conclusion. In this study, we explored the possibility that KXD for epilepsy may act on multiple targets through multiple active ingredients, involving neurotransmitters and neuroinflammatory pathways, providing a theoretical basis for subsequent clinical and experimental studies that will help develop effective new drugs to treat epilepsy.

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The Function of NF-Kappa B During Epilepsy, a Potential Therapeutic Target

Cited by 22 publications

References 161 publications

Eugenol alleviates neuronal damage via inhibiting inflammatory process against pilocarpine-induced status epilepticus

Eugenol alleviates neuronal damage via inhibiting inflammatory process against pilocarpine-induced status epilepticus

Sirtuin 3 regulates astrocyte activation by reducing Notch1 signaling after status epilepticus

Network Pharmacology and Molecular Docking to Explore the Mechanism of Kangxian Decoction for Epilepsy

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