Puerarin Improves Diabetic Aorta Injury by Inhibiting NADPH Oxidase-Derived Oxidative Stress in STZ-Induced Diabetic Rats

J Diabetes Res. 2016:2016:8541520. doi: 10.1155/2016/8541520. Epub 2016 Jan 6.

Abstract

Objective: Puerarin is a natural flavonoid isolated from the TCM lobed kudzuvine root. This study investigated the effect and mechanisms of puerarin on diabetic aorta in rats.

Methods: Streptozotocin- (STZ-) induced diabetic rats were administered with puerarin for 3 weeks. Levels of serum insulin (INS), PGE2, endothelin (ET), glycated hemoglobin (GHb), H2O2, and nitric oxide (NO) in rats were measured by ELISA and colorimetric assay kits. The aortas were stained with H&E. Moreover, the mRNA expression of ICAM-1, LOX-1, NADPH oxidase 2 (NOX2), and NOX4 and the protein expression of ICAM-1, LOX-1, NF-κB p65, E-selectin, NOX2, and NOX4 in aorta tissues were measured by real-time PCR and Western blot, respectively. The localization of ICAM-1, NF-κB p65, NOX2, and NOX4 in the aorta tissues was also determined through immunohistochemistry.

Results: Puerarin treatment exerted no effect on fasting blood glucose levels but significantly reduced the serum levels of INS, GHb, PGE2, ET, H2O2, and NO. In addition, puerarin improved the pathological alterations and inhibited the expression of ICAM-1, LOX-1, NOX2, and NOX4 at both mRNA and protein levels. Puerarin also significantly reduced the number of cells showing positive staining for ICAM-1, NOX2, NOX4, and NF-κB p65.

Conclusion: Puerarin demonstrated protective effect on the STZ-induced diabetic rat aorta. The protective mechanisms may include regulation of NF-κB and inhibition of NOX2 and NOX4 followed by inhibition of cell adhesion molecule expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aorta / physiopathology*
  • Blood Glucose / analysis
  • Body Weight
  • Cell Adhesion
  • Diabetes Complications
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / metabolism*
  • Endothelins / metabolism
  • Hemoglobins / metabolism
  • Hydrogen Peroxide / chemistry
  • Insulin / blood
  • Intercellular Adhesion Molecule-1 / metabolism
  • Isoflavones / chemistry*
  • Male
  • Membrane Glycoproteins / metabolism
  • NADPH Oxidase 2
  • NADPH Oxidase 4
  • NADPH Oxidases / metabolism*
  • NF-kappa B / metabolism
  • Neoplasm Proteins / metabolism
  • Nitric Oxide / metabolism
  • Nucleocytoplasmic Transport Proteins / metabolism
  • Oxidative Stress / drug effects*
  • Rats
  • Rats, Sprague-Dawley
  • Streptozocin
  • Vasodilator Agents / chemistry

Substances

  • Blood Glucose
  • Endothelins
  • Hemoglobins
  • ICAM1 protein, rat
  • Insulin
  • Isoflavones
  • Membrane Glycoproteins
  • NF-kappa B
  • Neoplasm Proteins
  • Nucleocytoplasmic Transport Proteins
  • Vasodilator Agents
  • p65 oncofetal mRNA transport protein, rat
  • Intercellular Adhesion Molecule-1
  • Nitric Oxide
  • Streptozocin
  • Hydrogen Peroxide
  • Cybb protein, rat
  • NADPH Oxidase 2
  • NADPH Oxidase 4
  • NADPH Oxidases
  • Nox4 protein, rat
  • puerarin