title: The effects of acute and repeated oroxylin A treatments on Abeta(25-35)-induced memory impairment in mice.
abstract: Oroxylin A is a flavonoid that is found in the roots of Scutellaria baicalensis Georgi. The aim of this study was to characterize the effects of oroxylin A on the memory impairments and pathological changes induced by Abeta(25-35) peptide in mice. The ameliorating effect of oroxylin A on memory impairment was investigated using passive avoidance and Y-maze tasks and pathological changes were identified by immunostaining and western blotting. Abeta(25-35) peptide (5nmol) was administered by intracerebroventricular injection. In the acute treatment study, a single dose of oroxylin A (5mg/kg, p.o.) treated 1h before behavioral tests was found to significantly reverse Abeta(25-35)-induced cognitive impairments based on passive avoidance and Y-maze task findings (P<0.05). Moreover, these acute effects of oroxylin A were blocked by diazepam (1mg/kg, i.p.), a GABA(A)/benzodiazepine binding site agonist (P<0.05). On the other hand, our subchronic studies revealed that oroxylin A (1 or 5mg/kg/day, p.o.) for 7 days ameliorated the memory impairment induced by Abeta(25-35) peptide. Moreover, Abeta(25-35)-induced increases in GFAP (an astroglia marker) and OX-42 (a microglia marker), and increases in iNOS positive cells in the hippocampus were found to be attenuated by subchronic oroxylin A (1 or 5mg/kg/day, i.p., P<0.05). In addition, reductions in the immunoreactivity and protein level of ChAT (a cholinergic neuronal cell marker) in the CA3 hippocampal area induced by Abeta(25-35) peptide were also attenuated by oroxylin A. Furthermore, lipid peroxidation induced by Abeta(25-35) was also reduced by oroxylin A. These results suggest that the amelioration of Abeta(25-35) peptide-induced memory impairment by oroxylin A is mediated via the GABAergic neurotransmitter system after a single administration, or by reductions in Abeta(25-35) peptide-induced astrocyte and microglia activations, iNOS expression, lipid peroxidation, and increased cholinergic neurotransmission after subchronic administration.
authors.affiliation: Department of Life and Nanopharmaceutical Sciences, College of Pharmacy, Kyung Hee University, Dongdaemoon-Ku, Seoul 130-701, Republic of Korea.
authors.forename: Dong Hyun
authors.initials: DH
authors.lastname: Kim
authors.forename: Sunho
authors.initials: S
authors.lastname: Kim
authors.forename: Su Jin
authors.initials: SJ
authors.lastname: Jeon
authors.forename: Kun Ho
authors.initials: KH
authors.lastname: Son
authors.forename: Seungjoo
authors.initials: S
authors.lastname: Lee
authors.forename: Byung Hoon
authors.initials: BH
authors.lastname: Yoon
authors.forename: Jae Hoon
authors.initials: JH
authors.lastname: Cheong
authors.forename: Kwang Ho
authors.initials: KH
authors.lastname: Ko
authors.forename: Jong Hoon
authors.initials: JH
authors.lastname: Ryu
mesh_terms: D016229:Amyloid beta-Peptides; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D039481:CD11b Antigen / Q000378:metabolism; D003975:Diazepam / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004791:Enzyme Inhibitors / Q000008:administration & dosage*; D005106:Exploratory Behavior / Q000187:drug effects; D005419:Flavonoids / Q000008:administration & dosage*; D016166:Free Radical Scavengers / Q000378:metabolism; D018757:GABA Modulators / Q000494:pharmacology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced* / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008813:Mice, Inbred ICR; D010446:Peptide Fragments; D011930:Reaction Time / Q000187:drug effects
chemical_list: D016229:Amyloid beta-Peptides; D039481:CD11b Antigen; D004791:Enzyme Inhibitors; D005419:Flavonoids; D016166:Free Radical Scavengers; D018757:GABA Modulators; D005904:Glial Fibrillary Acidic Protein; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); C080669:5,7-dihydroxy-6-methoxy-2-phenylchromen-4-one; D003975:Diazepam