Anti-amnesic effect of pseudoginsenoside-F11 in two mouse models of Alzheimer's disease

• Published in: Pharmacology, biochemistry and behavior biochemistry and behavior, 2013-05, Vol.106, p.57-67
• Main Authors: Wang, Chun-Ming, Liu, Ming-Yan, Wang, Fang, Wei, Min-Jie, Wang, Shuang, Wu, Chun-Fu, Yang, Jing-Yu
• Format: Article
• Language: English
• Subjects: Alzheimer Disease - drug therapy; Amnesia - drug therapy; Animals; Apoptosis; APP; APP/PS1 mice; Aβ1–42; Brain - drug effects; Caspase 3 - metabolism; Disease Models, Animal; Female; Ginsenosides - pharmacology; Ginsenosides - therapeutic use; Glutathione Peroxidase - metabolism; Male; Malondialdehyde - metabolism; Maze Learning; Mice; Mitogen-Activated Protein Kinase 9 - metabolism; Oxidative stress; Pseudoginsenoside-F11; Superoxide Dismutase - metabolism; Tumor Suppressor Protein p53 - metabolism
• ISSN: 0091-3057; 1873-5177
• DOI: 10.1016/j.pbb.2013.03.010

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 (410pmol) 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 15days at doses of 1.6 and 8mg/kg and APP/PS1 for 4weeks at a dose of 8mg/kg as measured by the Morris water maze and step-through tests. In APP/PS1 mice, PF11 8mg/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. [Display omitted] •PF11 protected learning and memory deficits induced by Aβ1-42 in KM mice.•PF11 improved learning and memory functions in APP/PS1 mice.•PF11 inhibited amyloidogenesis in cortex and hippocampus of APP/PS1 mice.•The anti-oxidation effect of PF11 was observed in cortex of APP/PS1 mice.•The anti-apoptosis effect of PF11 was disclosed in hippocampus of APP/PS1 mice.