Paeoniflorin Attenuates Amyloid-beta Peptide-induced Neurotoxicity by Ameliorating Oxidative Stress and Regulating the NGF-mediated Signaling in Rats

Paeoniflorin is a monoterpene glycoside isolated from the aqueous extract of the dry root of Paeonia. It has been identified to exhibit many pharmacological effects including enhancing the cognitive ability, producing anti-depressant-like effect and reducing the MTPT-induced toxicity. In our previous study, it has shown that paeoniflorin improved the cognitive ability and attenuated the oxidative stress in the Aβ(1-42)-treated rats. In order to further elucidate the possible molecular mechanisms of paeoniflorin on the cognitive ability, rats were injected with Aβ(1-42) (1 μg/μL) and later with paeoniflorin (15 mg/kg and 30 mg/kg, i.p.) and donepezil hydrochloride (2mg/kg, i.p.) daily for 20 days in this study. The results showed that the long-term treatment of paeoniflorin or donepezil enhanced the cognitive performances in the Morris water maze test, restored the decreased activities of superoxide dismutase and catalase and the increased level of malondialdehyde, and reversed the alterations of matrix metallopeptidase-9 and tissue-inhibitor of metalloproteinase-1 in the hippocampus of Aβ(1-42)-treated rats. Paeoniflorin also up-regulated the activity of choline acetyltrasferase and the expression of tyrosine kinase A receptor, and down-regulated the activity of acetylcholine esterase in the hippocampus of Aβ(1-42)-treated rats. These results demonstrate that paeoniflorin ameliorates the spatial learning and memory deficits by attenuating oxidative stress and regulating the nerve growth factor-mediated signaling to reinforce cholinergic functions in the hippocampus of the Aβ(1-42)-treated rats.