The effects of acute and repeated oroxylin A treatments on Aβ25-35-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 A beta(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. A beta(25-35) peptide (5 nmol) was administered by intra-cerebroventricular injection. In the acute treatment study, a single dose of oroxylin A (5 mg/kg, p.o.) treated 1 h before behavioral tests was found to significantly reverse A beta(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 (1 mg/kg, i.p.), a GABAA/benzodiazepine binding site agonist (P < 0.05). On the other hand, our subchronic studies revealed that oroxylin A (1 or 5 mg/kg/day, p.o.) for 7 days ameliorated the memory impairment induced by A beta(25-35) peptide. Moreover, A beta(25-35)-induced increases in GFAP (an astroglia marker) and OX-42 (a microglia marker), and increases in NOS positive cells in the hippocampus were found to be attenuated by subchronic oroxylin A (I or 5 mg/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 A beta(25-35) peptide were also attenuated by oroxylin A. Furthermore, lipid peroxidation induced by A beta(25-35) was also reduced by oroxylin A. These results suggest that the amelioration of A beta(25-35) peptide-induced memory impairment by oroxylin A is mediated via the GABAergic neurotransmitter system after a single administration, or by reductions in A beta(25-35) peptide-induced astrocyte and microglia activations, NOS expression, lipid peroxidation, and increased cholinergic neurotransmission after subchronic administration. (c) 2008 Published by Elsevier Ltd.