title: Puerarin suppresses production of nitric oxide and inducible nitric             oxide synthase in lipopolysaccharide-induced N9 microglial cells through regulating             MAPK phosphorylation, O-GlcNAcylation and NF-κB translocation.
abstract: Microglial cells play a critical role in mediating central nervous system             inﬂammatory processes. Activated microglial cells induced by proinflammatory factor,             such as lipopolysaccharide (LPS), release many kinds of neurotoxic cytokines including             reactive oxygen species (ROS) which contributes to the pathogenesis of neurodegenerative             diseases. Puerarin, extracted from kudzu root, possesses the characteristic of             neuroprotection, antioxidation and anticancer. In the present study, we observed             that LPS induced over-production of nitric oxide (NO) and increased the level             of intracellular ROS in N9 microglial cells, but it was inhibited by puerarin.             Furthermore, treatment with puerarin on N9 cells suppressed the over-expression             of inducible nitric oxide synthase (iNOS) induced by LPS which is implicated in             intracellular O-linked β-N-acetylglucosamine (O-GlcNAc) level, phosphorylation             of mitogen-activated protein kinase (MAPK) and nuclear factor κB (NF-κB) signaling             pathway. We also observed that the enhanced phosphorylation of p38, JNK and ERK1/2             in N9 cells induced by LPS were inhibited by puerarin, otherwise the down-regulation             of O-GlcNAcylation level of protein in N9 cell induced by LPS was up-regulated             by pretreatment with puerarin. These results indicate that puerarin effectively             inhibits microglia activation induced by LPS through inhibiting expression of             iNOS, production of NO and ROS which was mediated via regulating O-GlcNAcylation,             phosphorylation of MAPK and NF-κB translocation.
authors.affiliation: Department of Obstetrics and Gynecology, the Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, PR China.
authors.forename: Gao-Ming
authors.initials: GM
authors.lastname: Zheng
authors.forename: Chao
authors.initials: C
authors.lastname: Yu
authors.forename: Zhu
authors.initials: Z
authors.lastname: Yang
mesh_terms: D000117:Acetylglucosamine / Q000378:metabolism*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006031:Glycosylation; D007529:Isoflavones / Q000494:pharmacology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000201:enzymology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D017351:N-Acetylglucosaminyltransferases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation; D021381:Protein Transport; D017382:Reactive Oxygen Species / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D007529:Isoflavones; D008070:Lipopolysaccharides; D016328:NF-kappa B; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D017351:N-Acetylglucosaminyltransferases; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D000117:Acetylglucosamine; C033607:puerarin