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Engeletin protects against cerebral ischemia/reperfusion injury by modulating the VEGF/vasohibin and Ang-1/Tie-2 pathways.

Abstract
Engeletin is a natural derivative of Smilax glabra rhizomilax that exhibits anti-inflammatory activity and suppresses lipid peroxidation. In the present study, we sought to elucidate the mechanistic basis for the neuroprotective and pro-angiogenic activity of engeltin in a human umbilical vein endothelial cells (HUVECs) oxygen-glucose deprivation and reoxygenation (OGD/R) model system and a middle cerebral artery occlusion (MCAO) rat model of cerebral ischemia and reperfusion injury. These analyses revealed that engeletin (10, 20, or 40 mg/kg) was able to reduce the infarct volume, increase cerebral blood flow, improve neurological function, and bolster the expression of vascular endothelial growth factor (VEGF), vasohibin-2 (Vash-2), angiopoietin-1 (Ang-1), phosphorylated human angiopoietin receptor tyrosine kinase 2 (p-Tie2), and platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) in MCAO rats. Similarly, engeletin (100, 200, or 400 nM) markedly enhanced the migration, tube formation, and VEGF expression of HUVECs in an OGD/R model system, while the VEGF receptor (R) inhibitor axitinib reversed the observed changes in HUVEC tube formation activity and Vash-2, VEGF, and CD31 expression. These data suggested that engeletin exhibited significant neuroprotective effects against cerebral ischemia and reperfusion injury in rats, and improved cerebrovascular angiogenesis by modulating the VEGF/vasohibin and Ang-1/Tie-2 pathways.
AuthorsHui Liu, Shucui Li, Yangyang Xu, Xin Wang, Rui Ren, Haibo Zhu, Shuping Zhang
JournalBrazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas (Braz J Med Biol Res) Vol. 54 Issue 10 Pg. e11028 ( 2021) ISSN: 1414-431X [Electronic] Brazil
PMID34287581 (Publication Type: Journal Article)
Chemical References
  • Angiopoietin-1
  • Flavonols
  • Glycosides
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • engeletin
Topics
  • Angiopoietin-1
  • Animals
  • Brain Ischemia (prevention & control)
  • Endothelial Cells
  • Flavonols
  • Glycosides
  • Infarction, Middle Cerebral Artery
  • Rats
  • Reperfusion Injury (prevention & control)
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors

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