2-(4-Methoxyphenyl)Ethyl-2-Acetamido-2-Deoxy-β-d-Pyranoside Exerts a Neuroprotective Effect through Regulation of Energy Homeostasis and O-GlcNAcylation

  • Hui Xu
  • Huaxiang Gu
  • Yanhong Yang
  • Ergai Cai
  • Fei Ding
  • Shu YuEmail author


Dysfunction of energy metabolism exerts a central role in triggering neuron death following cerebral ischemia. Neuronal energy metabolism is highly dependent on glucose. O-GlcNAcylation, a post-translational modification, is a novel pro-survival pathway that modulates glucose homeostasis in ischemic stroke. Here, we explored whether activation O-GlcNAcylation and maintaining energy homeostasis mediated the neuroprotective effect of 2-(4-methoxyphenyl)ethyl-2-acetamido-2-deoxy-β-d-pyranoside, a synthetic salidroside analog (named SalA-4 g) which was previously developed in our laboratory. For in vivo analyses, SalA-4 g improved the outcome after transient middle cerebral artery occlusion (MCAO). 18F-FDG PET/MRI indicated that SalA-4 g accelerated the recovery of energy metabolism in the ipsilateral hippocampus in MCAO rats. In vitro analyses showed that glucose uptake was markedly increased, and O-GlcNAcylation was also activated by SalA-4 g in hippocampal neurons under both normal and oxygen glucose deprivation (OGD) conditions. Moreover, SalA-4 g exerted obvious neuroprotective effects in hippocampal neurons against moderate OGD injury. Our study indicates that boosting a pro-survival pathway—GlcNAcylation—and regulating energy homeostasis are important biochemical mechanisms responsible for SalA-4 g neuroprotection.


2-(4-Methoxyphenyl)ethyl-2-acetamido-2-deoxy-β-d-pyranoside Neuroprotection Energy homeostasis O-GlcNAcylation Ischemic stroke 



This work was supported by the National Key Basic Research Program of China (973 Program, Grant No. 2014CB542203), National Natural Science Foundation of China (Grant No. 81401094), and the Undergraduate Innovation Training Programs of Nantong University (Grant No. 201810304104X), a Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.


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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of NeuroregenerationNantong UniversityNantongPeople’s Republic of China

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