Antioxidant Blueberry Anthocyanins Induce Vasodilation via PI3K/Akt Signaling Pathway in High-Glucose-Induced Human Umbilical Vein Endothelial Cells

Int J Mol Sci. 2020 Feb 25;21(5):1575. doi: 10.3390/ijms21051575.

Abstract

Blueberries are rich in antioxidant anthocyanins. The hypotensive effects of blueberry anthocyanins in endothelial cells was investigated here. Pretreatment with blueberry anthocyanin extract, malvidin, malvidin-3-glucoside, and malvidin-3-galactoside significantly ameliorated high-glucose-induced damage by enhancing endogenous antioxidant superoxide dismutase (SOD) and heme oxygenase-1 (HO-1), lowering reactive oxygen species (ROS) generation and NADPH oxidase isoform 4 (NOX4) expression, and increasing the cell vitalities. They also effectively induced a vasodilatory effect by increasing the vasodilator nitric oxide (NO) and its promoters endothelial NO synthase (eNOS) and peroxisome proliferator-activated receptor-γ (PPARγ) levels as well as by decreasing the vasoconstrictor angiotensin-converting enzyme (ACE), xanthine oxidase-1 (XO-1), and low-density lipoprotein (LDL) levels. The activation of phosphoinositide 3-kinase (PI3K)/Akt signaling pathway and the breakdown of protein kinase C zeta (PKCζ) pathway were involved in the bioactivities. The results indicated blueberry anthocyanins protected endothelial function against high-glucose (HG) injury via antioxidant and vasodilatory mechanisms, which could be promising molecules as a hypotensive nutraceutical for diabetes patients.

Keywords: anthocyanin; antioxidant; blueberry; hypotensive; malvidin; vasodilatory.

MeSH terms

  • Anthocyanins / chemistry
  • Anthocyanins / pharmacology*
  • Antioxidants / chemistry
  • Antioxidants / pharmacology*
  • Blueberry Plants / chemistry*
  • Glucose / pharmacology
  • Human Umbilical Vein Endothelial Cells / drug effects*
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Lipoproteins, LDL / metabolism
  • Nitric Oxide / metabolism
  • Oxidative Stress
  • PPAR gamma / genetics
  • PPAR gamma / metabolism
  • Peptidyl-Dipeptidase A / genetics
  • Peptidyl-Dipeptidase A / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Protein Kinase C / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction*
  • Vasodilation*
  • Xanthine Oxidase / genetics
  • Xanthine Oxidase / metabolism

Substances

  • Anthocyanins
  • Antioxidants
  • Lipoproteins, LDL
  • PPAR gamma
  • Nitric Oxide
  • Xanthine Oxidase
  • Proto-Oncogene Proteins c-akt
  • protein kinase C zeta
  • Protein Kinase C
  • ACE protein, human
  • Peptidyl-Dipeptidase A
  • Glucose