Oxysophoridine protects against focal cerebral ischemic injury by inhibiting oxidative stress and apoptosis in mice.
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.
Teng-Fei
TF
Wang
Zhen
Z
Lei
Yu-Xiang
YX
Li
Yong-Sheng
YS
Wang
Jie
J
Wang
Shu-Jing
SJ
Wang
Yin-Ju
YJ
Hao
Ru
R
Zhou
Shao-Ju
SJ
Jin
Juan
J
Du
Juan
J
Li
Tao
T
Sun
Jian-Qiang
JQ
Yu
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002545:Brain Ischemia / Q000517:prevention & control*; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D018384:Oxidative Stress / Q000187:drug effects; D015427:Reperfusion Injury / Q000517:prevention & control*
D000470:Alkaloids; C406983:oxysophoridine