Research Paper Volume 12, Issue 13 pp 13422—13436

Codonopsis pilosula polysaccharide attenuates Aβ toxicity and cognitive defects in APP/PS1 mice

Lu Wan1, , Qing Zhang1, , Hongbin Luo2, , Zhendong Xu1, , Sheng Huang2, , Fumin Yang1, , Yi Liu1, , Yacoubou Abdoul Razak Mahaman1, , Dan Ke1, , Qun Wang1, , Rong Liu1, , Jian-Zhi Wang1,3, , Xiji Shu4, , Xiaochuan Wang1,3, ,

  • 1 Department of Pathophysiology, School of Basic Medicine, Key Laboratory of Education Ministry of China for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
  • 2 Medical College, Hubei University for Nationalities, Enshi 445000, HB, China
  • 3 Co-innovation Center of Neuroregeneration, Nantong University, Nantong 226001, JS, China
  • 4 Department of Pathology and Pathophysiology, School of Medicine, Jianghan University, Wuhan 430056, China

Received: February 13, 2020       Accepted: April 20, 2020       Published: July 11, 2020
How to Cite

Copyright © 2020 Wan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Codonopsis pilosula Polysaccharides (CPPs), a traditional Chinese medicine used for thousands of years, is a potential neuroprotective polysaccharide via a relatively poorly understood mechanism. We previously reported that CPPs attenuated tau pathology in hTau transfected mice and therefore in the current work investigated the effect of CPPs on Aβ toxicity and cognitive defects in APP/PS1 mice model. It was found that one-month intragastric administration of CPPs significantly ameliorated cognitive defects in APP/PS1 mice. In addition, CPPs treatment mitigated the loss of the synaptic plasticity and increased the synaptic proteins including synaptotagmin and PSD95. The expression of Aβ42 and Aβ40 was remarkably decreased in the hippocampus of APP/PS1 mice after CPPs treatment. We also found that CPPs coincubation significantly reduced the amount of APPβ and Aβ42 expression in cells. Intriguingly, the activity of BACE1 was decreased following CPPs treatment in both the hippocampus of APP/PS1 mice and in vitro experiments. Collectively, these results indicated that CPPs attenuated Aβ pathology in APP/PS1 mice, and down-regulating BACE1 might be the underlaying mechanism which could be a therapeutic target for alleviating cognitive defects in AD pathology.


CPPs: Codonopsis pilosula Polysaccharides; CP: Codonopsis pilosula; AD: Alzheimer’s disease; APP: Amyloid precursor protein; Aβ: Amyloid-β; BACE1: Beta amyloid precursor protein cleaving enzyme 1; SP: Senile plaque; NFTs: Neurofibrillary tangles; IG: Intragastric; WT: Wild-type; EPM: Elevated plus maze; NOR: Novel objective recognition; MWM: Morris water maze; SYT: Synaptotagmin; SYP: Synaptophysin; C99: C-terminal fragment; BBB: Blood-brain barrier.