Neurochemical Research

, Volume 43, Issue 9, pp 1736–1744 | Cite as

Neohesperidin Prevents Aβ25–35-Induced Apoptosis in Primary Cultured Hippocampal Neurons by Blocking the S-Nitrosylation of Protein-Disulphide Isomerase

  • Jijun Wang
  • Yingchun Yuan
  • Peng Zhang
  • Huixian Zhang
  • Xiaomei Liu
  • Yuelin ZhangEmail author
Original Paper


A growing body of literature has established a link between the cerebral ischaemic injury and pathological state of Alzheimer’s disease (AD), and this correlation indicated that the preventive agent for ischaemia might improve the pathology of AD. Our previous studies have demonstrated that Neohesperidin (NH) exhibited neuroprotective effects against cerebral ischemia via the down-regulation of Bcl-2, Akt/PI3K and Nrf2 pathways. In the present study, we first confirmed the protective effects of NH on Aβ25–35-induced neurotoxicity on primary cultured hippocampal neurons. We further demonstrated NH attenuated Aβ25–35-induced apoptosis by preventing neurotoxicity associated with lethal UPR and ER stress via blocking S-nitrosylation of protein-disulphide isomerase (PDI). These results suggested that S-nitrosylation of PDI and ER dysfunction might be the synergistic and synchronous pathological process between cerebral ischaemia and AD.


Neohesperidin 25–35 ER stress PDI S-Nitrosylation 



This work was financially supported by the Shaanxi Province Natural Science Foundation of China (S2015YFJM2252).

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no competing interests.

Supplementary material

11064_2018_2589_MOESM1_ESM.tif (1.5 mb)
Supplementary Fig. 1 Purity of primary rat hippocampal neurons. Purity of primary rat hippocampal neurons (8 DIV) was determined using double-label immunofluorescence for MAP2 and GFAP. The purity of primary rat hippocampal neurons (8 DIV) was more than 95% (TIF 1507 KB)
11064_2018_2589_MOESM2_ESM.tif (4.7 mb)
Supplementary Fig. 2 Double-label immunofluorescence for MAP-2 and p-PERK or CHOP. (A) Double-label immunofluorescence for MAP2 and p-PERK; (B) Double-label immunofluorescence for MAP2 and CHOP. (TIF 4802 KB)


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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of MedicineXi’an Jiaotong UniversityXi’anChina
  2. 2.Shaanxi Province People’s HospitalXi’anChina

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