Inulin with a low degree of polymerization protects human umbilical vein endothelial cells from hypoxia/reoxygenation-induced injury

Carbohydr Polym. 2019 Jul 15:216:97-106. doi: 10.1016/j.carbpol.2019.03.016. Epub 2019 Mar 30.

Abstract

Here, we identified inulin-type oligosaccharides with 3-13 degrees of polymerization from Morinda officinalis. Radical-scavenging assays showed that Inulins 4-7 had modest anti-oxidative effects. Inulins 4 and 5 dose-dependently increased human umbilical vein endothelial cell survival during hypoxia/re-oxygenation (H/R)-induced injury, and Inulin 5 promoted angiogenesis. Triplicate assays with the Affymetrix Human Transcriptome Array 2.0 showed that Inulin 5 exposure up-regulated genes associated with cell cycle progression, apoptosis, DNA replication and repair, ubiquitin-mediated proteolysis, the mitogen-activated protein kinase pathway, and the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)-signaling pathway. Flow cytometry, reverse transcription-quantitative polymerase chain reaction, and western blot experiments verified the microarray results and demonstrated that Inulin 5 influenced cell cycle progression and the PI3K-protein kinase B (PKB)-endothelial nitric oxide synthase (eNOS) pathway. Thus, inulin-type oligosaccharides from M. officinalis roots may protect against H/R-induced injury, primarily through an anti-oxidative effect, and promote angiogenesis by activating the PI3K-PKB-eNOS-signaling pathway.

Keywords: Angiogenesis; Anti-oxidation; Hypoxia/reoxygenation; Inulin; Morinda officinalis.

MeSH terms

  • Angiogenesis Inducing Agents / isolation & purification
  • Angiogenesis Inducing Agents / pharmacology
  • Carbohydrate Sequence
  • Cell Cycle / drug effects
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Free Radical Scavengers / isolation & purification
  • Free Radical Scavengers / pharmacology*
  • Gene Expression / drug effects
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Hypoxia / drug therapy*
  • Inulin / isolation & purification
  • Inulin / pharmacology*
  • Molecular Weight
  • Morinda / chemistry*
  • Nitric Oxide Synthase Type III / metabolism
  • Oligosaccharides / isolation & purification
  • Oligosaccharides / pharmacology*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphorylation / drug effects
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA, Messenger / metabolism
  • Signal Transduction / drug effects
  • Transcriptome / drug effects

Substances

  • Angiogenesis Inducing Agents
  • Cell Cycle Proteins
  • Free Radical Scavengers
  • Oligosaccharides
  • RNA, Messenger
  • Inulin
  • NOS3 protein, human
  • Nitric Oxide Synthase Type III
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt