title: Tetrandrine attenuates spatial memory impairment and hippocampal neuroinflammation via inhibiting NF-κB activation in a rat model of Alzheimer's disease induced by amyloid-β(1-42).
abstract: BACKGROUND
  The neuroinflammation characterized by glial activation and release of proinflammatory mediators is considered to play a critical role in the pathogenesis of Alzheimer's disease (AD). Tetrandrine, a bisbenzylisoquinoline alkaloid isolated from the Chinese herb radix Stephania tetrandra, has been demonstrated to decrease the expression of proinflammatory mediators by inhibition of nuclear factor-κB (NF-κB) activation. The purpose of the study was to investigate effects of tetrandrine on experimental model of AD.
  
  
  METHODS
  Tetrandrine was administered in a rat model of AD induced by amyloid-β (Aβ)(1-42). The learning and memory impairment was examined using Morris water maze; the extent of histological injury in hippocampus was determined by Nissl staining; NF-κB DNA binding activity was assessed by electrophoretic mobility shift assay; the expression of tumor necrosis factor (TNF)-α and interleukin (IL)-1β was measured by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  A significant improvement was observed in learning and memory impairment in rats with tetrandrine, and the increase in NF-κB DNA binding activity, the over-expression in IL-1β and TNF-α as well as the increased histological injury in hippocampus in rats induced by Aβ(1-42) were significantly reduced following administration of tetrandrine.
  
  
  CONCLUSIONS
  Tetrandrine could significantly ameliorate Aβ(1-42)-induced spatial learning and memory impairment, and the beneficial effect of tetrandrine treatment could be linked, at least in part, to the inhibition of NF-κB activity and the downregulation of expression of IL-1β and TNF-α, suggesting that administration of tetrandrine may provide a therapeutic approach for AD.
authors.affiliation: Department of Geriatrics Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, PR China.
authors.forename: Fu-Qian
authors.initials: FQ
authors.lastname: He
authors.forename: Bo-Yun
authors.initials: BY
authors.lastname: Qiu
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Zhang
authors.forename: Tian-Ke
authors.initials: TK
authors.lastname: Li
authors.forename: Qin
authors.initials: Q
authors.lastname: Xie
authors.forename: De-Jun
authors.initials: DJ
authors.lastname: Cui
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Huang
authors.forename: Hua-Tian
authors.initials: HT
authors.lastname: Gan
mesh_terms: D000255:Adenosine Triphosphate / Q000493:pharmacokinetics; D000544:Alzheimer Disease / Q000139:chemically induced / Q000150:complications* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000633:toxicity; D000704:Analysis of Variance; D000818:Animals; D044182:Benzylisoquinolines / Q000627:therapeutic use*; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004347:Drug Interactions; D024202:Electrophoretic Mobility Shift Assay / Q000379:methods; D004660:Encephalitis / Q000188:drug therapy* / Q000209:etiology; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000473:pathology*; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000188:drug therapy* / Q000209:etiology; D016328:NF-kappa B / Q000378:metabolism; D009474:Neurons / Q000473:pathology; D010446:Peptide Fragments / Q000633:toxicity; D010759:Phosphorus Isotopes / Q000493:pharmacokinetics; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D044182:Benzylisoquinolines; D002121:Calcium Channel Blockers; D053583:Interleukin-1beta; D016328:NF-kappa B; D010446:Peptide Fragments; D010759:Phosphorus Isotopes; D014409:Tumor Necrosis Factor-alpha; C075222:amyloid beta-protein (1-42); C009438:tetrandrine; D000255:Adenosine Triphosphate