Apigenin Protects the Brain against Ischemia/Reperfusion Injury via Caveolin-1/VEGF In Vitro and In Vivo

Oxid Med Cell Longev. 2018 Dec 3:2018:7017204. doi: 10.1155/2018/7017204. eCollection 2018.

Abstract

Apigenin is a natural flavonoid found in several dietary plant foods as vegetables and fruits. To investigate potential anti-ischemia/reperfusion injury properties of apigenin in vitro, cell proliferation assay, tube formation, cell migration, apoptosis, and autophagy were performed in human brain microvascular endothelial cells (HBMVECs) after oxygen-glucose deprivation/reoxygenation (OGD/R). The effect of apigenin was also explored in rats after middle cerebral artery occlusion/reperfusion (MCAO/R) via neurobehavioral scores, pathological examination, and measurement of markers involved in ischemia/reperfusion injury. Data in vitro indicated that apigenin could prompt cell proliferation, tube formation, and cell migration while inhibiting apoptosis and autophagy by affecting Caveolin-1/VEGF, Bcl-2, Caspase-3, Beclin-1, and mTOR expression. Results in vivo showed that apigenin significantly reduced neurobehavioral scores and volume of cerebral infarction while prompting vascular endothelial cell proliferation by upregulating VEGFR2/CD34 double-labeling endothelial progenitor cell (EPC) number and affecting Caveolin-1, VEGF, and eNOS expression in brain tissue of MCAO/R rats. All the data suggested that apigenin may be protective for the brain against ischemia/reperfusion injury by alleviating apoptosis and autophagy, promoting cell proliferation in HBMVECs of OGD/R, and attenuating brain damage and improved neurological function in rats of MCAO/R through the Caveolin-1/VEGF pathway.

MeSH terms

  • Animals
  • Apigenin / pharmacology
  • Apigenin / therapeutic use*
  • Cardiovascular Diseases / complications*
  • Caveolin 1 / metabolism*
  • Flavonoids / pharmacology
  • Flavonoids / therapeutic use*
  • Humans
  • Male
  • Rats
  • Reperfusion Injury / drug therapy*
  • Reperfusion Injury / pathology
  • Vascular Endothelial Growth Factor A / metabolism*

Substances

  • Caveolin 1
  • Flavonoids
  • Vascular Endothelial Growth Factor A
  • Apigenin