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http://dx.doi.org/10.1016/j.jgr.2020.07.003

20(S)-protopanaxadiol and oleanolic acid ameliorate cognitive deficits in APP/PS1 transgenic mice by enhancing hippocampal neurogenesis  

Lin, Kaili (School of Public Health, Guangzhou Medical University)
Sze, Stephen Cho-Wing (Department of Biology, Faculty of Science, Hong Kong Baptist University (HKBU), Kowloon Tong, Hong Kong Special Administrative Region (HKSAR))
Liu, Bin (Guangzhou Institute of Cardiovascular Disease, The Second Affiliated Hospital of Guangzhou Medical University)
Zhang, Zhang (Department of Biology, Faculty of Science, Hong Kong Baptist University (HKBU), Kowloon Tong, Hong Kong Special Administrative Region (HKSAR))
Zhang, Zhu (Department of Biology, Faculty of Science, Hong Kong Baptist University (HKBU), Kowloon Tong, Hong Kong Special Administrative Region (HKSAR))
Zhu, Peili (Department of Biology, Faculty of Science, Hong Kong Baptist University (HKBU), Kowloon Tong, Hong Kong Special Administrative Region (HKSAR))
Wang, Ying (Department of Biology, Faculty of Science, Hong Kong Baptist University (HKBU), Kowloon Tong, Hong Kong Special Administrative Region (HKSAR))
Deng, Qiudi (GMU-GIBH Joint School of Life Sciences, Guangzhou Medical University)
Yung, Ken Kin-Lam (Department of Biology, Faculty of Science, Hong Kong Baptist University (HKBU), Kowloon Tong, Hong Kong Special Administrative Region (HKSAR))
Zhang, Shiqing (Department of Biology, Faculty of Science, Hong Kong Baptist University (HKBU), Kowloon Tong, Hong Kong Special Administrative Region (HKSAR))
Publication Information
Journal of Ginseng Research / v.45, no.2, 2021 , pp. 325-333 More about this Journal
Abstract
Background: Alzheimer's disease (AD) is one of the most prevalent neurodegenerative disorders. Enhancing hippocampal neurogenesis by promoting proliferation and differentiation of neural stem cells (NSCs) is a promising therapeutic strategy for AD. 20(S)-protopanaxadiol (PPD) and oleanolic acid (OA) are small, bioactive compounds found in ginseng that can promote NSC proliferation and neural differentiation in vitro. However, it is currently unknown whether PPD or OA can attenuate cognitive deficits by enhancing hippocampal neurogenesis in vivo in a transgenic APP/PS1 AD mouse model. Here, we administered PPD or OA to APP/PS1 mice and monitored the effects on cognition and hippocampal neurogenesis. Methods: We used the Morris water maze, Y maze, and open field tests to compare the cognitive capacities of treated and untreated APP/PS1 mice. We investigated hippocampal neurogenesis using Nissl staining and BrdU/NeuN double labeling. NSC proliferation was quantified by Sox2 labeling of the hippocampal dentate gyrus. We used western blotting to determine the effects of PPD and OA on Wnt/GSK3β/β-catenin pathway activation in the hippocampus. Results: Both PPD and OA significantly ameliorated the cognitive impairments observed in untreated APP/PS1 mice. Furthermore, PPD and OA significantly promoted hippocampal neurogenesis and NSC proliferation. At the mechanistic level, PPD and OA treatments resulted in Wnt/GSK-3β/β-catenin pathway activation in the hippocampus. Conclusion: PPD and OA ameliorate cognitive deficits in APP/PS1 mice by enhancing hippocampal neurogenesis, achieved by stimulating the Wnt/GSK-3β/β-catenin pathway. As such, PPD and OA are promising novel therapeutic agents for the treatment of AD and other neurodegenerative diseases.
Keywords
Alzheimer's disease; 20(S)-protopanaxadiol; oleanolic acid; cognitive deficits; hippocampal neurogenesis;
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