Neuroprotective Effect of AM404 Against NMDA-Induced Hippocampal Excitotoxicity

Saliba, Soraya Wilke; Bonifacino, Tiziana; Serchov, Tsvetan; Bonanno, Giambattista; Oliveira, Antônio Carlos Pinheiro de; Fiebich, Bernd L.

doi:10.3389/fncel.2019.00566

Cited by 15 publications

(11 citation statements)

References 62 publications

(64 reference statements)

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“…In murine 4-aminopyridine-induced epileptic hippocampal neurons, AM404 reduced anandamide- and capsaicin-induced Ca 2+ -accumulation, apoptosis and ROS-generation ( Nazıroğlu et al, 2019 ). In our previous studies, we showed the reduction of LPS-induced PGE 2 and 8-isoprostane release by AM404 in concentration-dependent manner in primary rat microglia ( Saliba et al, 2017 ) and N-methyl-D-aspartate (NMDA)-induced IL-1β-expression in organotypic hippocampal slice cultures (OHSC) of mouse brain ( Saliba et al, 2019 ). Furthermore, COX-2 protein levels and COX-activity induced by LPS were significantly reduced by AM404.…”

Section: Introductionmentioning

confidence: 99%

Anti-Inflammatory and Anti-Oxidative Effects of AM404 in IL-1β-Stimulated SK-N-SH Neuroblastoma Cells

Apweiler¹,

Streyczek²,

Saliba³

et al. 2021

Front. Pharmacol.

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An emerging number of studies address the involvement of neuroinflammation and oxidative stress in the pathophysiology of central nervous system (CNS) disorders such as depression, schizophrenia, anxiety, and neurodegenerative diseases. Different cytokines and molecules, such as prostaglandin (PG) E2, are associated with neuroinflammatory processes. The active acetaminophen metabolite AM404 has been shown to prevent inflammation and neuroinflammation in primary microglia and organotypic hippocampal slice cultures. However, its effects on pathophysiological conditions in the CNS and especially on neurons are still poorly understood. In this study, we therefore evaluated the effects of AM404 and acetaminophen on the arachidonic acid cascade and oxidative stress induced by interleukin (IL)-1β in human SK-N-SH neuronal cells. We observed that AM404 and acetaminophen significantly and concentration-dependent inhibited IL-1β-induced release of PGE2, independent of cyclooxygenases (COX)-1 and COX-2 enzymatic activity as well as COX-2 mRNA and protein levels in SK-N-SH-cells. The reduction of IL-1β-induced PGE2-release by AM404 and acetaminophen treatment might be mediated by the 8-iso-PGF2α pathway since IL-1β-induced synthesis of this free radical marker is dose-dependently reduced by both compounds, respectively. Therefore, understanding of the potential therapeutic properties of AM404 in neuroinflammation and oxidative stress might lead to future treatment options of different neurological disorders.

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Section: Introductionmentioning

confidence: 99%

Anti-Inflammatory and Anti-Oxidative Effects of AM404 in IL-1β-Stimulated SK-N-SH Neuroblastoma Cells

Apweiler¹,

Streyczek²,

Saliba³

et al. 2021

Front. Pharmacol.

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“…The way in which NO and eicosanoid biosynthesis pathways are linked is not yet known 165‐167 . Moreover, recent studies have shown that AM404 exhibits a neuroprotective effect against NMDA‐induced hippocampal excitotoxicity, and could find application as a neuroprotective agent in Huntington's and Parkinson's diseases and ischaemia 67,168 …”

Section: Paracetamol – Other Mechanisms Of Actionmentioning

confidence: 99%

Paracetamol – An old drug with new mechanisms of action

Przybyła

Szychowski

Gmiński

2020

Clin Exp Pharma Physio

104

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Paracetamol (which is a recommended international nonproprietary name of acetaminophen (acetyl-p-aminophenol, APAP)), was synthesized in 1878 by Morse and first introduced into medicine as an antipyretic/analgesic by Von Mering in 1893. 1-3 Initially, it was rarely used in favor of phenacetin. However, after discovering that paracetamol is the main metabolite of phenacetin with better tolerance vs. phenacetin nephrotoxicity, in the 1950s paracetamol replaced phenacetin in use 4-6 and has become a widespread drug since then. Prostaglandins are mainly mediators of inflammatory pain. 7,8 The enzymes responsible for the synthesis of these mediators are called cyclooxygenases. 9 In 1971, John Vane identified the first cyclooxygenase (COX-1). 10 This discovery helped explain the mechanism of action of aspirin, which has been extensively used since 1899 as an analgesic and anti-inflammatory drug. 10 Afterwards, in 1991, Xie et al at Daniel Simmons's laboratory, Brigham Young University, discovered the second cyclooxygenase (COX-2). 11,12 Interestingly, the structure of the COX-2 enzyme did not differ substantially from the previously discovered COX-1. 13 However, they have different clinical significance. 14,15 Finally, in 2002, Chandrasekharan et al discovered

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“…VB-037 is a quinoline compound protecting neurons against Aβ aggregates-induced cytotoxicity through reduction of P38- and JNK-mediated inflammation [ 30 ]. In addition, anandamide transport inhibitor AM404 (C 26 H 37 NO 2 ) displays anti-inflammatory and neuroprotection effects on N-methyl-D-aspartic acid (NMDA)-induced excitotoxicity [ 31 ]. In the present study, we examined the anti-inflammatory effects of AM404, VB-037, glycyrrhizic acid, SG-Tang, and G. inflata on BV-2 microglia and inducible A53T SNCA-GFP-expressing SH-SY5Y cells.…”

Section: Introductionmentioning

confidence: 99%

Pathomechanism Characterization and Potential Therapeutics Identification for Parkinson’s Disease Targeting Neuroinflammation

Chen

Yen

Chen

et al. 2021

IJMS

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Parkinson’s disease (PD) is a common neurodegenerative disorder characterized by the loss of dopaminergic (DAergic) neurons and the presence of α-synuclein-containing Lewy bodies. The unstructured α-synuclein forms insoluble fibrils and aggregates that result in increased reactive oxygen species (ROS) and cellular toxicity in PD. Neuroinflammation engaged by microglia actively contributes to the pathogenesis of PD. In this study, we showed that VB-037 (a quinoline compound), glycyrrhetic acid (a pentacyclic triterpenoid), Glycyrrhiza inflata (G. inflata, a Chinese herbal medicine), and Shaoyao Gancao Tang (SG-Tang, a formulated Chinese medicine) suppressed the nitric oxide (NO) production and interleukin (IL)-1β maturation in α-synuclein-stimulated BV-2 cells. Mouse inflammation antibody array further revealed increased IL-1α, IL-1β, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) expression in α-synuclein-inflamed BV-2 cells and compound pretreatment effectively reduced the expression and release of these pro-inflammatory mediators. The test compounds and herbal medicines further reduced α-synuclein aggregation and associated oxidative stress, and protected cells against α-synuclein-induced neurotoxicity by downregulating NLR family pyrin domain containing 1 (NLRP1) and 3 (NLRP3), caspase 1, IL-1β, IL-6, and associated nuclear factor (NF)-κB inhibitor alpha (IκBα)/NF-κB P65 subunit (P65), c-Jun N-terminal kinase (JNK)/proto-oncogene c-Jun (JUN), mitogen-activated protein kinase 14 (P38)/signal transducer and activator of transcription 1 (STAT1) and Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathways in dopaminergic neurons derived from α-synuclein-expressing SH-SY5Y cells. Our findings indicate the potential of VB-037, glycyrrhetic acid, G. inflata, and SG-Tang through mitigating α-synuclein-stimulated neuroinflammation in PD, as new drug candidates for PD treatment.

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Neuroprotective Effect of AM404 Against NMDA-Induced Hippocampal Excitotoxicity

Cited by 15 publications

References 62 publications

Anti-Inflammatory and Anti-Oxidative Effects of AM404 in IL-1β-Stimulated SK-N-SH Neuroblastoma Cells

Anti-Inflammatory and Anti-Oxidative Effects of AM404 in IL-1β-Stimulated SK-N-SH Neuroblastoma Cells

Paracetamol – An old drug with new mechanisms of action

Pathomechanism Characterization and Potential Therapeutics Identification for Parkinson’s Disease Targeting Neuroinflammation

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