title: Troxerutin counteracts domoic acid-induced memory deficits in mice by inhibiting CCAAT/enhancer binding protein β-mediated inflammatory response and oxidative stress.
abstract: The C/EBP β is a basic leucine zipper transcription factor that regulates a variety of biological processes, including metabolism, cell proliferation and differentiation, and immune response. Recent findings show that C/EBP β-induced inflammatory responses mediate kainic acid-triggered excitotoxic brain injury. In this article, we show that protein kinase C ζ enhances K-ras expression and subsequently activates the Raf/MEK/ERK1/2 pathway in the hippocampus of domoic acid (DA)-treated mice, which promotes C/EBP β expression and induces inflammatory responses. Elevated production of TNF-α impairs mitochondrial function and increases the levels of reactive oxygen species by IκB kinase β/NF-κB signaling. The aforementioned inflammation and oxidative stress lead to memory deficits in DA-treated mice. However, troxerutin inhibits cyclin-dependent kinase 1 expression, enhances type 1 protein phosphatase α dephosphorylation, and abolishes MEK/ERK1/2/C/EBP β activation, which subsequently reverses the memory impairment observed in the DA-treated mice. Thus, troxerutin is recommended as a potential candidate for the prevention and therapeutic treatment of cognitive deficits resulting from excitotoxic brain damage and other brain disorders.
authors: Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Xuzhou Normal University, Xuzhou 221116, Jiangsu Province, People's Republic of China.
authors: Jun
authors: J
authors: Lu
authors: Dong-mei
authors: DM
authors: Wu
authors: Yuan-lin
authors: YL
authors: Zheng
authors: Bin
authors: B
authors: Hu
authors: Wei
authors: W
authors: Cheng
authors: Zi-feng
authors: ZF
authors: Zhang
authors: Meng-qiu
authors: MQ
authors: Li
mesh_terms: D000818:Animals; D002070:Butadienes / Q000494:pharmacology; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics / Q000378:metabolism*; D016203:CDC2 Protein Kinase / Q000378:metabolism; D055785:Gene Knockdown Techniques; D011905:Genes, ras; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006896:Hydroxyethylrutoside / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D007249:Inflammation / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism; D007608:Kainic Acid / Q000009:adverse effects; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D019255:NADPH Oxidases / Q000235:genetics; D009570:Nitriles / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects*; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D000099221:Protein Kinase C zeta
chemical_list: D002070:Butadienes; D022782:CCAAT-Enhancer-Binding Protein-beta; D016203:CDC2 Protein Kinase; D006896:Hydroxyethylrutoside; D018836:Inflammation Mediators; D007608:Kainic Acid; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D019255:NADPH Oxidases; D009570:Nitriles; D010749:Phosphoprotein Phosphatases; D011493:Protein Kinase C; D017382:Reactive Oxygen Species; D000099221:Protein Kinase C zeta; C113580:U 0126; C005865:troxerutin; C060505:neutrophil cytosolic factor 1