title: Effects of luteolin on spatial memory, cell proliferation, and neuroblast differentiation in the hippocampal dentate gyrus in a scopolamine-induced amnesia model.
abstract: OBJECTIVE
  Luteolin, a common flavonoid from many plants, has various pharmacological activities, including a memory-improving effect. In this study, we investigated the effects of luteolin on spatial memory, cell proliferation, and neuroblast differentiation in the hippocampal dentate gyrus in a rat model of scopolamine (SCO)-induced amnesia.
  
  
  METHODS
  Scopolamine was subcutaneously administered for 28 days via an Alzet minipump (44 mg/ml delivered at 2·5 μl/h) along with a daily intraperitoneal administration of vehicle (saline) 10 mg/kg luteolin or 5 mg/kg galantamine (GAL) (a control drug for acetylcholinesterase (AChE) inhibitor) for 28 days.
  
  
  RESULTS
  The administration of SCO significantly decreased the spatial alteration percentage in the Y-maze test compared to that in the vehicle (saline)-treated group. The administration of luteolin or GAL significantly improved the spatial alteration percentage compared to that in the SCO-treated group. Similarly, the administration of SCO significantly decreased the cell proliferation (Ki67-positive cells) and neuroblast differentiation (doubleocortin-positive cells) in the dentate gyrus. The administration of luteolin or GAL significantly mitigated the SCO-induced reduction of Ki67- and doublecortin-immunoreactive cells in the dentate gyrus. In addition, the administration of luteolin significantly decreased the lipid peroxidation (malondialdehyde (MDA) levels) and increased the brain-derived neurotrophic factor (BDNF) and AChE levels in the hippocampal homogenates compared to the SCO-treated group.
  
  
  CONCLUSIONS
  These results suggest that the luteolin treatment improves the SCO-induced reduction of cell proliferation and neuroblast differentiation in the dentate gyrus. The mechanism underlying the amelioration of SCO-induced amnesia by luteolin may be associated with the increase in BDNF, acetylcholine, and the decrease in lipid peroxidation.
authors: Seoul National University, Seoul, South Korea.
authors: Dae Young
authors: DY
authors: Yoo
authors: Jung Hoon
authors: JH
authors: Choi
authors: Woosuk
authors: W
authors: Kim
authors: Sung Min
authors: SM
authors: Nam
authors: Hyo Young
authors: HY
authors: Jung
authors: Jong Hwi
authors: JH
authors: Kim
authors: Moo-Ho
authors: MH
authors: Won
authors: Yeo Sung
authors: YS
authors: Yoon
authors: In Koo
authors: IK
authors: Hwang
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000647:Amnesia / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology*; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D018891:Dentate Gyrus / Q000166:cytology / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D000089662:Doublecortin Protein; D005702:Galantamine / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects; D047311:Luteolin / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D018782:Maze Learning; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy*; D055495:Neurogenesis / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D012601:Scopolamine
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D002800:Cholinesterase Inhibitors; C000714848:Dcx protein, rat; D000089662:Doublecortin Protein; D018696:Neuroprotective Agents; D005702:Galantamine; D012601:Scopolamine; D000110:Acetylcholinesterase; D047311:Luteolin