title: Protection by genistein on cortical neurons against oxidative stress injury via inhibition of NF-kappaB, JNK and ERK signaling pathway.
abstract: BACKGROUND
  Genistein, one of the isoflavones derived from soybean seeds, has been reported to exert multiple bioactivities. However, the mechanism of its action on the central nervous system is not fully understood.
  
  
  OBJECTIVE
  To investigate the cytoprotection of genistein and its molecular mechanism against H2O2-induced cell death in primary rat cortical neurons.
  
  
  METHODS
  Genistein (0.01, 0.1, and 1 μM) were added into the primary rat neurons 24 h before and co-cultured with 500 μM H2O2 for 1 h. Neuronal injury was assessed by MTT, lactate dehydrogenase (LDH) assay, and Hoechst33258 staining. Intracellular reactive oxygen species (ROS) generation induced by H2O2 was determined. Neuronal apoptosis was evaluated by Bcl-2/Bax ratio as well as by caspase-9 and caspase-3 activities. The protein levels and phosphorylation of NF-κB/p65, IκB, JNK, and ERK were detected by western blots.
  
  
  RESULTS
  Genistein pretreatment attenuated H2O2-mediated neuronal viability loss, nuclear condensation, and ROS generation in a concentration-dependent manner. Genistein exerted anti-apoptotic effects by reversing the apoptotic factors Bcl-2 and Bax ratio, along with the suppression of caspase-9 and caspase-3 activities. In addition, genistein down-regulated the expression of NF-κB/p65, and suppressed the phosphorylation of p65 and IκB. Genistein also inhibited H2O2-induced activation of the MAPK-signaling pathway including JNK and ERK.
  
  
  CONCLUSIONS
  The results indicated that genistein effectively protects cortical neurons against oxidative stress at least partly via inactivation of NF-κB as well as MAPK-signaling pathways, and suggested the possibility of this antioxidant for the prevention and treatment of stroke.
authors.affiliation: Institute of Translational Medicine, Nanchang University, Honggu District , Nanchang , PR China .
authors.forename: Yisong
authors.initials: Y
authors.lastname: Qian
authors.forename: Liangxun
authors.initials: L
authors.lastname: Cao
authors.forename: Teng
authors.initials: T
authors.lastname: Guan
authors.forename: Lan
authors.initials: L
authors.lastname: Chen
authors.forename: Hongbo
authors.initials: H
authors.lastname: Xin
authors.forename: Yunman
authors.initials: Y
authors.lastname: Li
authors.forename: Rui
authors.initials: R
authors.lastname: Zheng
authors.forename: Deyue
authors.initials: D
authors.lastname: Yu
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D019833:Genistein / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000502:physiology; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000975:Antioxidants; D016328:NF-kappa B; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D019833:Genistein
keywords: Apoptosis; MAPK; NF-κB; reactive oxygen species