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Neurochemical Research

, Volume 38, Issue 11, pp 2408–2417 | Cite as

Oxysophoridine Protects Against Focal Cerebral Ischemic Injury by Inhibiting Oxidative Stress and Apoptosis in Mice

  • Teng-Fei Wang
  • Zhen Lei
  • Yu-Xiang Li
  • Yong-Sheng Wang
  • Jie Wang
  • Shu-Jing Wang
  • Yin-Ju Hao
  • Ru Zhou
  • Shao-Ju Jin
  • Juan Du
  • Juan Li
  • Tao Sun
  • Jian-Qiang Yu
Original Paper

Abstract

Our previous studies have demonstrated that oxysophoridine (OSR) has protective effects on cerebral neurons damage in vitro induced by oxygen and glucose deprivation. In this study, we further investigated whether OSR could reduce ischemic cerebral injury in vivo and its possible mechanism. Male Institute of cancer research mice were intraperitoneally injected with OSR (62.5, 125 and 250 mg/kg) for seven successive days, then subjected to brain ischemia induced by the model of middle cerebral artery occlusion. After reperfusion, neurological scores and infarct volume were estimated. Morphological examination of tissues was performed. Apoptotic neurons were detected by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling staining. Oxidative stress levels were assessed by measurement of malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels. The expression of various apoptotic markers as Caspase-3, Bax and Bcl-2 were investigated by immunohistochemistry and Western-blot analysis. OSR pretreatment groups significantly reduced infract volume and neurological deficit scores. OSR decreased the percentage of apoptotic neurons, relieved neuronal morphological damage. Moreover, OSR markedly decreased MDA content, and increased SOD, GSH-Px activities. Administration of OSR (250 mg/kg) significantly suppressed overexpression of Caspase-3 and Bax, and increased Bcl-2 expression. These findings indicate that OSR has a protective effect on focal cerebral ischemic injury through antioxidant and anti-apoptotic mechanisms.

Keywords

Oxysophoridine Cerebral ischemic injury Oxidative stress Neuronal apoptosis 

Abbreviations

ECA

External carotid artery

ECL

Enhanced chemiluminescence

GSH-Px

Glutathione peroxidase

HE

Hematoxylin-eosin staining

ICA

Internal carotid artery

ICR

Institute of cancer research

MCA

Middle cerebral artery

MCAO

Middle cerebral artery occlusion

MDA

Malondialdehyde

OSR

Oxysophoridine

PVDF

Transferred onto a polyvinylidene difluoride

SDS-PAGE

Sodium dodecyl sulfate-polyacrylamide gel electrophoresis

SOD

Superoxide dismutase

TTC

2,3,5-Triphenyl tetrazolium chloride

TUNEL

Terminal deoxynucleotidyl transferase mediated dUTP nick end labeling

Notes

Acknowledgments

The authors gratefully acknowledge the financial supported by the National Natural Science Foundation of China (Grant No. 309605060, 81160524, 81360649), the Natural Science Foundation of Ningxia (Grant No. NZ11212) and Ningxia Hui Autonomous Region, colleges and universities of science and technology research projects (NGY2012055). We are indebted to the staff in the animal center and the Science & Technology Centre who provided assistance in the study.

Conflict of interest

The authors declare that they have no competing interests.

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Teng-Fei Wang
    • 1
  • Zhen Lei
    • 1
  • Yu-Xiang Li
    • 2
  • Yong-Sheng Wang
    • 1
  • Jie Wang
    • 3
  • Shu-Jing Wang
    • 3
  • Yin-Ju Hao
    • 1
  • Ru Zhou
    • 1
  • Shao-Ju Jin
    • 1
  • Juan Du
    • 1
  • Juan Li
    • 1
  • Tao Sun
    • 4
  • Jian-Qiang Yu
    • 1
    • 2
  1. 1.Department of PharmacologyNingxia Medical UniversityYinchuanPeople’s Republic of China
  2. 2.Shanghai Pudong New Area Gongli HospitalShanghaiPeople’s Republic of China
  3. 3.Technology CentreNingxia Medical UniversityYinchuanPeople’s Republic of China
  4. 4.Ningxia Key Lab of Craniocerebral Diseases of Ningxia Hui Autonomous RegionNingxia Medical UniversityYinchuanPeople’s Republic of China

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