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.
Sodium dodecyl sulfate-polyacrylamide gel electrophoresis
2,3,5-Triphenyl tetrazolium chloride
Terminal deoxynucleotidyl transferase mediated dUTP nick end labeling
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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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