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

J Cell Mol Med. 2021 Oct;25(20):9753-9766. doi: 10.1111/jcmm.16923. Epub 2021 Sep 12.

Abstract

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)/GSK3β(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.

Keywords: Nrf-2; endothelial cell; ischaemic stroke; oridonin; oxidative stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Biomarkers
  • Blood-Brain Barrier / metabolism
  • Capillary Permeability
  • Cell Survival / drug effects
  • Disease Models, Animal
  • Disease Susceptibility
  • Diterpenes, Kaurane / pharmacology*
  • Endothelium / drug effects
  • Endothelium / metabolism*
  • Endothelium / pathology
  • Glucose / metabolism
  • Glycogen Synthase Kinase 3 beta / metabolism
  • Immunohistochemistry
  • Ischemic Stroke / etiology
  • Ischemic Stroke / metabolism*
  • Male
  • Mice
  • NF-E2-Related Factor 2 / metabolism*
  • Neurons / drug effects
  • Neurons / metabolism
  • Oxidative Stress / drug effects*
  • Oxygen / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / drug effects*

Substances

  • Anti-Inflammatory Agents
  • Biomarkers
  • Diterpenes, Kaurane
  • NF-E2-Related Factor 2
  • Reactive Oxygen Species
  • oridonin
  • Glycogen Synthase Kinase 3 beta
  • Proto-Oncogene Proteins c-akt
  • Glucose
  • Oxygen