Journal
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
Volume 25, Issue 20, Pages 9753-9766Publisher
WILEY
DOI: 10.1111/jcmm.16923
Keywords
endothelial cell; ischaemic stroke; Nrf-2; oridonin; oxidative stress
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Funding
- Natural Science Foundation of the Jiangsu Higher Education Institutions of China [18KJA310004]
- Medical Research Project of Jiangsu Commission of Health [ZDA2020006]
- Priority Academic Program Development of Jiangsu Higher Education Institutions
- National Natural Science Foundation of China [81973301, 82003732, 81773701]
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Oridonin, a natural compound extracted from a Chinese herb, has been shown to protect against oxidative stress-induced endothelial injury by promoting nuclear translocation of Nrf-2. It repairs the blood-brain barrier and reduces infarct volume in ischemic stroke mice by activating signaling pathways. These findings suggest the potential therapeutic effect of oridonin in ischemic stroke treatment.
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.
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