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Metabolic Brain Disease

, Volume 33, Issue 6, pp 1869–1875 | Cite as

Oxymatrine attenuates brain hypoxic-ischemic injury from apoptosis and oxidative stress: role of p-Akt/GSK3β/HO-1/Nrf-2 signaling pathway

  • Xu-Hua Ge
  • Li Shao
  • Guo-Ji Zhu
Original Article
  • 104 Downloads

Abstract

To investigate the potential neuroprotection of oxymatrine in hypoxic-ischemic injury in rat’s brain and the associated underlying mechanisms, modified neurological severity scores (mNSS) for neurological functional deficits, 2,3,5-triphenyl-tetrazolium chloride (TTC) staining for infarct volume, TUNEL assay and flow cytometry analysis for apoptosis were assessed. The expressions of Akt, glycogen synthase kinase 3 beta (GSK3β), phosphorylated Akt (p-Akt), phosphorylated GSK3β (p-GSK3β), nuclear factor erythroid 2-related factor 2 (Nrf2) and hemeoxygenase-1 (HO-1) were measured by western blot. Our results showed that infarct volume and the apoptosis of NeuN-positive cells were significantly reduced in rats that administrated oxymatrine, with a corresponding improvement in neurological function after H/I. Upregulated p-Akt, p-GSK3β, Nrf-2 and HO-1 expressions were observed in response to oxymatrine treatment. Moreover, the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 counteracted the protective effect of oxymatrine, evidenced by western blot and histological outcomes. To conclude, our results suggested that oxymatrine could exert efficacious neuroprotective effect against H/I injury by inhibiting apoptosis and oxidative stress, which might be related to the activation of Akt and GSK3β and modulation of Nrf-2/HO-1 signaling pathway.

Keywords

Oxymatrine Hypoxic-ischemic injury Apoptosis Akt/GSK3β pathway Nrf2/HO-1 pathway 

Notes

Funding

This work was sponsored by the National Natural Science Foundation of China (81370254).

Compliance with ethical standards

Declaration of conflicting interests

The authors declare that they have no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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

Authors and Affiliations

  1. 1.Department of General medicine, Yangpu HospitalTongji University School of MedicineShanghaiPeople’s Republic of China
  2. 2.Department of Neruology, Xuzhou First People’s HospitalThe Municipal Hospital Affiliated to Xuzhou Medical UniversityXuzhouPeople’s Republic of China
  3. 3.Department of Internal MedicineSoochow University Affiliated Children’s HospitalSuzhouPeople’s Republic of China

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