title: Anti-amnesic effect of pseudoginsenoside-F11 in two mouse models of Alzheimer's disease.
abstract: Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by amyloid β (Aβ) deposits, elevated oxidative stress, and apoptosis of the neurons. Pseudoginsenoside-F11 (PF11), a component of Panax quinquefolium (American ginseng), has been demonstrated to antagonize the learning and memory deficits induced by scopolamine, morphine and methamphetamine in mice. In the present study, we investigated the effect of PF11 on AD-like cognitive impairment both in mice induced by intracerebroventricular injection of Aβ1-42 (410 pmol) and in Tg-APPswe/PS1dE9 (APP/PS1) mice. It was found that oral treatment with PF11 significantly mitigated learning and memory impairment in mice given Aβ1-42-treated mice for 15 days at doses of 1.6 and 8 mg/kg and APP/PS1 for 4 weeks at a dose of 8 mg/kg as measured by the Morris water maze and step-through tests. In APP/PS1 mice, PF11 8 mg/kg significantly inhibited the expressions of β-amyloid precursor protein (APP) and Aβ1-40 in the cortex and hippocampus, restored the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and decreased the production of malondialdehyde (MDA) in the cortex. It also noticeably improved the histopathological changes in the cortex and hippocampus and downregulated the expressions of JNK 2, p53 and cleaved caspase 3 in the hippocampus. These findings suggested that the inhibitory effect on amyloidogenesis and oxidative stress and some beneficial effects on neuronal functions might contribute to the recognition improvement effect of PF11 in APP/PS1 mice. Cumulatively, the present study indicated that PF11 may serve as a potential therapeutic agent for the treatment of AD.
authors.affiliation: Department of Pharmacology, Shenyang Pharmaceutical University, 110016, Shenyang, PR China.
authors.forename: Chun-Ming
authors.initials: CM
authors.lastname: Wang
authors.forename: Ming-Yan
authors.initials: MY
authors.lastname: Liu
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.forename: Min-Jie
authors.initials: MJ
authors.lastname: Wei
authors.forename: Shuang
authors.initials: S
authors.lastname: Wang
authors.forename: Chun-Fu
authors.initials: CF
authors.lastname: Wu
authors.forename: Jing-Yu
authors.initials: JY
authors.lastname: Yang
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy*; D000647:Amnesia / Q000188:drug therapy*; D000818:Animals; D001921:Brain / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D036145:Ginsenosides / Q000494:pharmacology / Q000627:therapeutic use*; D005979:Glutathione Peroxidase / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018782:Maze Learning; D051379:Mice; D048056:Mitogen-Activated Protein Kinase 9 / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D036145:Ginsenosides; D016159:Tumor Suppressor Protein p53; C413985:pseudoginsenoside F11; D008315:Malondialdehyde; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D048056:Mitogen-Activated Protein Kinase 9; D053148:Caspase 3