Codonopsis pilosula Polysaccharide Attenuates Tau Hyperphosphorylation and Cognitive Impairments in hTau Infected Mice.

Qing Zhang,Dan Ke,Yiyuan Xia,Qun Wang,Sheng Huang,Bin Zhang,Yongjun Wang,Yangping Shentu,Jian-Zhi Wang,Yacoubou Abdoul Razak Mahaman,Fang Huang,Rong Liu,Xiaochuan Wang,Hongbin Luo

doi:10.3389/fnmol.2018.00437

Abstract

Codonopsis pilosula polysaccharide (CPPs), a natural products with potentially lower toxicity and better bioavailability has been used in traditional Chinese medicine for 1000s of years and a neuroprotective polysaccharide mitigates tau pathology in Alzheimer’s disease (AD) mouse model. However, whether CPPs can relieve AD pathology and cognitive defects remains poorly understood. Here we reported that CPPs remarkably increased the cell viability and PP2A activity, decreased tau phosphorylation in HEK 293/tau cells. Next, we employed an adeno-associated virus serotype 2 (AAV2)-induced expression of human full length tau (hTau) in C57/BL6 mice to mimic AD tau pathology. One month intragastric administration of CPPs significantly increased PP2A activity and reduced tau phosphorylation at Ser199, Ser202/Thr205 (AT8) and Thr231 in hippocampus of AAV2-hTau infected mice. Furthermore, behavioral tests revealed that CPPs rescued hTau overexpression induced cognitive defects while CPPs significantly increased the fEPSP slope and synaptic proteins including synaptotagmin and synaptophysin. Together, our data suggest that CPPs might prevent AD-like tau hyperphosphorylation via activation of PP2A and attenuates AD-like cognitive impairments through restoring the synaptic plasticity and synaptogenesis. In conclusion, our findings suggest that CPPs might be a potential candidate compound for the treatment of tau related diseases.

Highlights

Alzheimer’s disease (AD) is a kind of neurodegenerative illness with progressive cognitive impairment (Reitz et al, 2011)
CCK-8 assay showed that all the relative survival rates in HEK293/tau cells treated with the different concentration of Codonopsis pilosula polysaccharide (CPPs) were significantly increased compared to control group (Figure 1A), supporting that CPPs upregulates cell viability
Alzheimer’s disease is one of chronic and neurodegenerative disorders that is histopathologically characterized by Aβ plaques and neurofibrillary tangles (NFTs), which lead a progressive deterioration of cognition and behavior (Janus et al, 2001)

Summary

Introduction

Alzheimer’s disease (AD) is a kind of neurodegenerative illness with progressive cognitive impairment (Reitz et al, 2011). NFTs is positively correlated with the severity of clinical dementia in AD, implicating hyperphosphorylation is Codonopsis pilosula Polysaccharide Blocks Tau Pathology a potent inducer of tau pathology (Arriagada et al, 1992). As the main bioactive components of CP extracts, the CP polysaccharide (CPP) is identified as a major constituent responsible for the therapeutic function of CP, such as antitumor, antimicrobial, immunoenhancing and antioxidant functions (Liu et al, 1988; Luo et al, 2007; Zong et al, 2012). Other previous study have shown that polysaccharides from different plants alleviate cognitive impairment and pathological alterations in AD animal models (Ho et al, 2010; Zhang et al, 2016). Whether CPPs ameliorates AD pathological process, especially tau pathology is not investigated yet

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Conclusion