The anti-amnesic effects of luteolin against amyloid beta(25-35) peptide-induced toxicity in mice involve the protection of neurovascular unit.
Luteolin (3',4',5,7-tetrahydroxyflavone) is an important member of the flavonoid family. It exhibits strongly anti-inflammatory, antioxidant and phytoestrogen-like activities. In the present study, we examined the anti-amnesic and protective effects of luteolin against Abeta(25-35)-induced toxicity in mice. Mice were given an i.c.v. injection of aggregated Abeta(25-35) peptide. The learning and memory impairments, ultrastructural changes of cerebral cortex, cerebrovascular dysfunction and neuronal changes were detected after oral administration of luteolin continuously for 8 days. Our results demonstrate that oral administration of luteolin for 8 days for those Abeta(25-35)-induced amnesic mice conferred robust neurovascular protection in Abeta(25-35)-induced amnesia, involving the improvement of the spatial learning and memory capabilities, the modulation of microvascular function, the increase of regional cerebral blood flow values, the clearance of reactive oxygen species, the improvement of cholinergic neuronal system, and the increase of brain-derived neurotrophic factor level and its receptor tyrosine kinase B expression in cerebral cortex.
Liu
R
R
National Center for Pharmaceutical Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Xiannongtan Street, Beijing 100050, China.
Gao
M
M
Qiang
G-F
GF
Zhang
T-T
TT
Lan
X
X
Ying
J
J
Du
G-H
GH
D000109:Acetylcholine / Q000378:metabolism; D000110:Acetylcholinesterase / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000502:physiology* / Q000633:toxicity; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002196:Capillaries / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D002199:Capillary Permeability / Q000187:drug effects; D002540:Cerebral Cortex / Q000098:blood supply / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects; D062507:Claudin-5; D047311:Luteolin / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008565:Membrane Proteins / Q000096:biosynthesis; D008568:Memory / Q000187:drug effects*; D051379:Mice; D018697:Nootropic Agents / Q000494:pharmacology*; D062793:Occludin; D010446:Peptide Fragments / Q000502:physiology* / Q000633:toxicity; D010750:Phosphoproteins / Q000096:biosynthesis; D017382:Reactive Oxygen Species / Q000378:metabolism; D020813:Receptor, trkB / Q000096:biosynthesis; D013037:Spatial Behavior / Q000187:drug effects; D062826:Zonula Occludens-1 Protein
D016229:Amyloid beta-Peptides; D019208:Brain-Derived Neurotrophic Factor; D062507:Claudin-5; C491511:Cldn5 protein, mouse; D008565:Membrane Proteins; D018697:Nootropic Agents; D062793:Occludin; C568986:Ocln protein, mouse; D010446:Peptide Fragments; D010750:Phosphoproteins; D017382:Reactive Oxygen Species; C569043:Tjp1 protein, mouse; D062826:Zonula Occludens-1 Protein; C074636:amyloid beta-protein (25-35); D020813:Receptor, trkB; D000110:Acetylcholinesterase; D047311:Luteolin; D000109:Acetylcholine