The effects of acute and repeated oroxylin A treatments on Abeta(25-35)-induced memory impairment in mice.
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.
Kim
Dong Hyun
DH
Department of Life and Nanopharmaceutical Sciences, College of Pharmacy, Kyung Hee University, Dongdaemoon-Ku, Seoul 130-701, Republic of Korea.
Kim
Sunho
S
Jeon
Su Jin
SJ
Son
Kun Ho
KH
Lee
Seungjoo
S
Yoon
Byung Hoon
BH
Cheong
Jae Hoon
JH
Ko
Kwang Ho
KH
Ryu
Jong Hoon
JH
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
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