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 Aβ25–35 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. Aβ25–35 peptide (5 nmol) was administered by intracerebroventricular 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 Aβ25–35-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 Aβ25–35 peptide. Moreover, Aβ25–35-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 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 Aβ25–35 peptide were also attenuated by oroxylin A. Furthermore, lipid peroxidation induced by Aβ25–35 was also reduced by oroxylin A. These results suggest that the amelioration of Aβ25–35 peptide-induced memory impairment by oroxylin A is mediated via the GABAergic neurotransmitter system after a single administration, or by reductions in Aβ25–35 peptide-induced astrocyte and microglia activations, iNOS expression, lipid peroxidation, and increased cholinergic neurotransmission after subchronic administration.