Resveratrol ameliorates diabetic vascular inflammation and macrophage infiltration in db/db mice by inhibiting the NF-κB pathway

Diab Vasc Dis Res. 2014 Mar;11(2):92-102. doi: 10.1177/1479164113520332. Epub 2014 Jan 23.

Abstract

In this study, resveratrol (RSV) - a potent sirtuin 1 activator - was found to have beneficial effects on glucolipid metabolism and improve inflammatory mediators and markers of oxidative stress. Diabetic (db/db) mice and non-diabetic C57BL/6J mice were used in the study. The db/db mice were treated with or without 0.3% RSV mixed with chow for 8 weeks. Dietary RSV significantly lowered blood glucose, plasma lipid and free fatty acid levels in db/db mice. RSV markedly inhibited the expression of intercellular adhesion molecule-1 (ICAM-1), endothelial vascular cell adhesion molecule-1 (VCAM-1) and monocyte chemoattractant protein-1 (MCP-1) in the aorta and the blood plasma of db/db mice (p < 0.05). Levels of mac-3-positive macrophages (measure of the infiltration of activated macrophages) were lower in RSV-treated diabetic mice than in their untreated counterparts (p < 0.05). RSV treatment reduced the activity of the transcriptional regulator nuclear factor kappa B (NF-κB) in aortic tissues (p < 0.05). Thus, RSV treatment reduced ICAM-1, VCAM-1 and MCP-1 expression in the aorta and ICAM-1, VCAM-1 and MCP-1 levels in the plasma of diabetic mice. Since dietary supplementation with RSV also reduced NF-κB activities in the aorta, the therapeutic effects of RSV might be associated with the downregulation of NF-κB.

Keywords: Diabetes; NF-κB; SIRT1; resveratrol; vascular inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Differentiation / metabolism
  • Blood Glucose / metabolism
  • Chemokine CCL2 / drug effects*
  • Chemokine CCL2 / metabolism
  • Diabetes Complications / metabolism*
  • Diabetes Mellitus
  • Inflammation / drug therapy
  • Intercellular Adhesion Molecule-1 / metabolism
  • Macrophages / drug effects*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • NF-kappa B / metabolism
  • Resveratrol
  • Signal Transduction / drug effects*
  • Stilbenes / pharmacology*
  • Vascular Cell Adhesion Molecule-1 / metabolism

Substances

  • Antigens, Differentiation
  • Blood Glucose
  • Chemokine CCL2
  • NF-kappa B
  • Stilbenes
  • Vascular Cell Adhesion Molecule-1
  • monocyte-macrophage differentiation antigen
  • Intercellular Adhesion Molecule-1
  • Resveratrol