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Neurochemical Research

, Volume 44, Issue 12, pp 2708–2722 | Cite as

Icariin Ameliorates Amyloid Pathologies by Maintaining Homeostasis of Autophagic Systems in Aβ1–42-Injected Rats

  • Xia JiangEmail author
  • Lin-Lin Chen
  • Zhou Lan
  • Fan Xiong
  • Xiang Xu
  • Yang-Yang Yin
  • Ping Li
  • Ping WangEmail author
Original Paper

Abstract

Macroautophagy, a sole pathway for dysfunctional organelles or aggregated proteins turnover, has been implicated in the early development of Alzheimer’s disease (AD). Previous studies have found that reversal of autophagy dysfunction in APP transgenic mice ameliorates amyloid pathologies. Icariin (ICA), the main component from traditional Chinese herb Epimedium brevicornu Maxim., can reduce accumulations of amyloid-β (Aβ) peptide in vivo and in vitro, but the mechanism remains unclear. Here, we explored the effects of ICA on autophagy-lysosomal pathway in intracerebroventricular (icv) injection of human Aβ1–42 peptide rats. We demonstrated that feeding the rats with ICA (30 mg/kg, 60 mg/kg and 90 mg/kg rat, per os) for 4 weeks rescued the Aβ1–42-induced spatial memory impairments, reduced endogenous rat Aβ42 tested by ELISA and decreased Aβ accumulation using 6E10 antibody. Furthermore, Aβ1–42 induced strong autophagy response, however ICA decreased the levels of microtubule-associated protein 1 light chain 3 (LC3) II/LC3I, Beclin1, Cathepsin D (Cat D) and brain lysosomal Cathepsin D activity. We also observed that ICA enhanced the phosphorylation of protein kinase B (PKB/AKT) and p70 ribosomal protein S6 kinase (p70S6K). In addition, ICA arrested Aβ1–42-induced cells loss, mitochondrias damage, nuclear membranes unclear and abundant nucleas chromatin agglutinates in hippocampus, lessened the expression of Cleaved-caspase-3, brain oxidative stress, astroglial activation. These findings suggest that ICA can ameliorate amyloid pathologies with improving autophagy-lysosome function and Chinese materia medica may be potential for AD treatment.

Keywords

Alzheimer’s disease Memory deficit Autophagy Aβ Protein aggregation 

Notes

Acknowledgements

This work was supported by National Natural Science Foundation of China (81303252, 81573865), Hubei Provincial Natural Science Foundation of China (2017CFB733) and China Postdoctoral Science Special Foundation (2016T90685).

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no potential conflicts of interest to disclose.

Supplementary material

11064_2019_2889_MOESM1_ESM.docx (22.3 mb)
Supplementary material 1 (DOCX 22861 kb)

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Authors and Affiliations

  1. 1.Department of PathologyHubei University of Chinese MedicineWuhanPeople’s Republic of China
  2. 2.New products of TCM senile Diseases Co-innovation Center of HubeiWuhanPeople’s Republic of China

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