Oridonin prevents oxidative stress-induced endothelial injury via promoting Nrf-2 pathway in ischaemic stroke

被引:24
|
作者
Li, Lei [1 ]
Cheng, Shu-Qi [1 ]
Guo, Wei [1 ]
Cai, Zhen-Yu [1 ]
Sun, Yu-Qin [1 ]
Huang, Xin-Xin [2 ]
Yang, Jin [1 ]
Ji, Juan [1 ]
Chen, Ya-Yun [1 ]
Dong, Yin-Feng [3 ]
Cheng, Hong [2 ]
Sun, Xiu-Lan [1 ,3 ]
机构
[1] Nanjing Med Univ, Neuroprotect Drug Discovery Key Lab, Jiangsu Key Lab Neurodegenerat, Nanjing, Peoples R China
[2] Nanjing Med Univ, Affiliated Hosp 1, Nanjing, Peoples R China
[3] Nanjing Univ Chinese Med, Affiliated Hosp, Nanjing, Peoples R China
基金
中国国家自然科学基金;
关键词
endothelial cell; ischaemic stroke; Nrf-2; oridonin; oxidative stress; BLOOD-BRAIN-BARRIER; REPERFUSION INJURY; DISRUPTION; DISEASE; APOPTOSIS; AUTOPHAGY; HEALTH;
D O I
10.1111/jcmm.16923
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Oridonin, a natural diterpenoid compound extracted from a Chinese herb, has been proved to exert anti-oxidative stress effects in various disease models. The aim of the present study was to investigate the protective effects of oridonin on oxidative stress-induced endothelial injury in ischaemic stroke. We found oridonin repaired blood-brain barrier (BBB) integrity presented with upregulation of tight junction proteins (TJ proteins) expression, inhibited the infiltration of periphery inflammatory cells and neuroinflammation and thereby reduced infarct volume in ischaemic stroke mice. Furthermore, our results showed that oridonin could protect against oxidative stress-induced endothelial injury via promoting nuclear translocation of nuclear factor-erythroid 2 related factor 2 (Nrf-2). The specific mechanism could be the activation of AKT(Ser473)/GSK3 beta(Ser9)/Fyn signalling pathway. Our findings revealed the therapeutic effect and mechanism of oridonin in ischaemic stroke, which provided fundamental evidence for developing the extracted compound of Chinese herbal medicine into an innovative drug for ischaemic stroke treatment.
引用
收藏
页码:9753 / 9766
页数:14
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