Salvianolic acid B improves the disruption of high glucose-mediated brain microvascular endothelial cells via the ROS/HIF-1α/VEGF and miR-200b/VEGF signaling pathways

Neurosci Lett. 2016 Sep 6:630:233-240. doi: 10.1016/j.neulet.2016.08.005. Epub 2016 Aug 3.

Abstract

The study investigated the roles and mechanisms of Salvianolic acid B (Sal B) on permeability of rat brain microvascular endothelial cells (RBMECs) exposed to high glucose. The results demonstrated that Sal B greatly up-regulated the expression of tight junction (TJ) proteins and decreased the permeability of RBMECs compared with the control group. And the increase of reactive oxidative species (ROS) production, the upregulation of hypoxia-inducible factor-1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF) protein induced by high glucose were antagonized by Sal B. In addition, a great decrease of microRNA-200b (miR-200b) was observed in the RBMECs under high-glucose condition, which was significantly increased by Sal B pretreatment. And overexpression of miR-200b markedly attenuated the RBMECs permeability and inhibited the expression of VEGF protein by targeting with 3'-UTR of its mRNA. This led to the conclusion that Sal B-mediated improvement of blood-brain barrier dysfunction induced by high-glucose is related to the ROS/HIF-1α/VEGF and miR-200b/VEGF signaling pathways.

Keywords: HIF-1α; High glucose; Salvianolic acid B; Tight junction proteins; miR-200b.

MeSH terms

  • Animals
  • Benzofurans / administration & dosage*
  • Blood-Brain Barrier / drug effects*
  • Blood-Brain Barrier / metabolism*
  • Cells, Cultured
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Glucose / administration & dosage
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
  • MicroRNAs / metabolism*
  • Microvessels / drug effects
  • Microvessels / metabolism
  • Occludin / metabolism
  • RNA, Messenger / metabolism
  • Rats
  • Reactive Oxygen Species / metabolism*
  • Signal Transduction / drug effects
  • Up-Regulation / drug effects
  • Vascular Endothelial Growth Factor A / metabolism*
  • Zonula Occludens-1 Protein / metabolism

Substances

  • Benzofurans
  • Hif1a protein, rat
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • MIRN200 microRNA, rat
  • MicroRNAs
  • Occludin
  • Ocln protein, rat
  • RNA, Messenger
  • Reactive Oxygen Species
  • Tjp1 protein, rat
  • Vascular Endothelial Growth Factor A
  • Zonula Occludens-1 Protein
  • vascular endothelial growth factor A, rat
  • salvianolic acid B
  • Glucose