title: Rutin, A Natural Flavonoid Protects PC12 Cells Against Sodium Nitroprusside-Induced Neurotoxicity Through Activating PI3K/Akt/mTOR and ERK1/2 Pathway.
abstract: Free radicals induced neural damage is implicated in CNS diseases and rutin isolated form Lonicera japonica are reported to have neuroprotective activity. Previously, we confirmed that rutin exerted neuroprotective effect against sodium nitroprusside (SNP)-induced cell death in PC12 cells. However, the neuroprotective mechanism of rutin is still not fully uncovered. Here, we found that rutin significantly decreased SNP-induced reactive oxygen species in PC12 cells. Rutin reversed the declined GSH/GSSG ratio and mitochondrial membrane potential induced by SNP. Moreover, rutin activated both the protein Akt/mTOR and the extracellular signal-regulated kinase (ERK1/2) signaling pathways and the neuroprotective effects of rutin were blocked by either the specific PI3K inhibitor LY294002 or the MAPK pathway inhibitor PD98059. In summary, these results demonstrated that the neuroprotective effects of rutin might be through activating both the PI3K/Akt/mTOR and ERK1/2 signaling pathways. Our findings support that rutin may have therapeutic potential for the treatment of CNS diseases related to NO neurotoxicity.
authors.affiliation: National Pharmaceutical Engineering Center for Solid Preparation in Chinese Herbal Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang, 330006, People's Republic of China.
authors.forename: Rikang
authors.initials: R
authors.lastname: Wang
authors.forename: Yongbing
authors.initials: Y
authors.lastname: Sun
authors.forename: Hesong
authors.initials: H
authors.lastname: Huang
authors.forename: Lan
authors.initials: L
authors.lastname: Wang
authors.forename: Jinlong
authors.initials: J
authors.lastname: Chen
authors.forename: Wei
authors.initials: W
authors.lastname: Shen
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D020935:MAP Kinase Signaling System; D009599:Nitroprusside / Q000633:toxicity*; D016716:PC12 Cells; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D012431:Rutin / Q000494:pharmacology*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D009599:Nitroprusside; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D017382:Reactive Oxygen Species; D012431:Rutin; D058570:TOR Serine-Threonine Kinases