Sulforaphane reduces advanced glycation end products (AGEs)-induced inflammation in endothelial cells and rat aorta

Nutr Metab Cardiovasc Dis. 2016 Sep;26(9):797-807. doi: 10.1016/j.numecd.2016.04.008. Epub 2016 Apr 21.


Background and aims: Advanced glycation end products (AGEs)-receptor RAGE interaction evokes oxidative stress and inflammatory reactions, thereby being involved in endothelial cell (EC) damage in diabetes. Sulforaphane is generated from glucoraphanin, a naturally occurring isothiocyanate found in widely consumed cruciferous vegetables, by myrosinase. Sulforaphane has been reported to protect against oxidative stress-mediated cell and tissue injury. However, effects of sulforaphane on AGEs-induced vascular damage remain unclear.

Methods and results: In this study, we investigated whether and how sulforaphane could inhibit inflammation in AGEs-exposed human umbilical vein ECs (HUVECs) and AGEs-injected rat aorta. Sulforaphane treatment for 4 or 24 h dose-dependently inhibited the AGEs-induced increase in RAGE, monocyte chemoattractant protein-1 (MCP-1), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecular-1 (VCAM-1) gene expression in HUVECs. AGEs significantly stimulated MCP-1 production by, and THP-1 cell adhesion to, HUVECs, both of which were prevented by 1.6 μM sulforaphane. Sulforaphane significantly suppressed oxidative stress generation and NADPH oxidase activation evoked by AGEs in HUVECs. Furthermore, aortic RAGE, ICAM-1 and VCAM-1 expression in AGEs-injected rats were increased, which were suppressed by simultaneous infusion of sulforaphane.

Conclusion: The present study demonstrated for the first time that sulforaphane could inhibit inflammation in AGEs-exposed HUVECs and AGEs-infused rat aorta partly by suppressing RAGE expression through its anti-oxidative properties. Inhibition of the AGEs-RAGE axis by sulforaphane might be a novel therapeutic target for vascular injury in diabetes.

Keywords: AGEs; Atherosclerosis; Oxidative stress; RAGE; Sulforaphane.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Antioxidants / pharmacology*
  • Aorta / drug effects*
  • Aorta / metabolism
  • Aortitis / chemically induced
  • Aortitis / metabolism
  • Aortitis / prevention & control*
  • Cell Adhesion Molecules / metabolism
  • Cell Line, Tumor
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Endothelial Cells / drug effects*
  • Endothelial Cells / metabolism
  • Glycation End Products, Advanced*
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Inflammation Mediators / metabolism
  • Isothiocyanates / pharmacology*
  • Male
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats, Wistar
  • Receptor for Advanced Glycation End Products / drug effects
  • Receptor for Advanced Glycation End Products / genetics
  • Receptor for Advanced Glycation End Products / metabolism
  • Time Factors


  • AGER protein, human
  • Ager protein, rat
  • Anti-Inflammatory Agents
  • Antioxidants
  • Cell Adhesion Molecules
  • Glycation End Products, Advanced
  • Inflammation Mediators
  • Isothiocyanates
  • RNA, Messenger
  • Receptor for Advanced Glycation End Products
  • sulforaphane