Peoniflorin attentuates Aβ(1-42)-mediated neurotoxicity by regulating calcium homeostasis and ameliorating oxidative stress in hippocampus of rats

Peoniflorin (PEF), a monoterpene glycoside isolated from the aqueous extract of the dry root of Paeonia, possesses wide pharmacological effects in nervous system. In this study, by using a developed rat model of hippocampal dysfunction induced by intrahippocampal injection of A beta((1-42)) oligomers, we investigated whether PEF exerted protection against A beta-induced neurotoxicity. A stereotactic intrahippocampal bilateral injection of A beta((1-42)) (5 mu g per side) was performed in Sprague-Dawley rats (250-280 g). A beta((1-42))-exposed rats showed remarkable memory impairment in Morris water maze test and neuronal apoptosis by in situ terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling in hippocampus. Chronic treatment with PEF (7.5, 15 and 30 mg/(kg day), for 20 days, intraperitoneally) significantly and dose-dependently attenuated cognitive deficit, ameliorated cell apoptosis in A beta((1-42))-treated rats. The neuroprotective effect of PEF was closely associated with its activities of maintenance of [Ca2(+)](i) homeostasis, increase of reduced glutathione (GSH) content, suppression of NOS activity and nitric oxide (NO) level, decrease of carbonyl protein (CP) and malondialdehyde (MDA) levels. These results suggested that PEF possessed the activity of prevention of the neurotoxicity induced by A beta((1-42)) and might exert beneficial action for the treatment of Alzheimer's disease (AD). (C) 2009 Elsevier B.V. All rights reserved.