[go: up one dir, main page]

Quercetin protects against diabetes-induced exaggerated vasoconstriction in rats: effect on low grade inflammation

PLoS One. 2013 May 22;8(5):e63784. doi: 10.1371/journal.pone.0063784. Print 2013.

Abstract

Vascular complications are the leading cause of morbidity and mortality in patients with diabetes. Quercetin is an important flavonoid with antioxidant and anti-inflammatory activity. Here, the effect of quercetin on diabetes-induced exaggerated vasoconstriction in insulin deficient and insulin resistant rat models was investigated. Insulin deficiency was induced by streptozotocin while, insulin resistance by fructose. Rats were left 8 weeks or 12 weeks after STZ or fructose administration respectively. Quercetin was daily administered in the last 6 weeks. Then, tail blood pressure (BP) was recorded in conscious animals; concentration-response curves for phenylephrine (PE) and KCl were studied in thoracic aorta rings. Non-fasting blood glucose level, serum insulin level, insulin resistance index, serum tumour necrosis factor-α (TNF-α) and serum C-reactive protein (CRP) were determined. Nuclear transcription factor-κB (NF-κB) was assessed by immunofluorescence technique. Histopathological examination was also performed. The results showed that quercetin protected against diabetes-induced exaggerated vasoconstriction and reduced the elevated blood pressure. In addition, quercetin inhibited diabetes associated adventitial leukocyte infiltration, endothelial pyknosis and increased collagen deposition. These effects were accompanied with reduction in serum level of both TNF-α and CRP and inhibition of aortic NF-κB by quercetin in both models of diabetes. On the other hand, quercetin did not affect glucose level in any of the used diabetic models. This suggests that the protective effect of quercetin is mediated by its anti-inflammatory effect rather than its metabolic effects. In summary, quercetin is potential candidate to prevent diabetic vascular complications in both insulin deficiency and resistance via its inhibitory effect on inflammatory pathways especially NF-κB signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Antioxidants / pharmacology
  • Aorta, Thoracic / drug effects
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Blood Pressure / drug effects
  • C-Reactive Protein / metabolism
  • Collagen / metabolism
  • Diabetes Mellitus, Experimental / blood
  • Diabetes Mellitus, Experimental / complications*
  • Diabetic Angiopathies / blood
  • Diabetic Angiopathies / drug therapy*
  • Endothelium / drug effects
  • Endothelium / metabolism
  • Hypoglycemic Agents / pharmacology
  • Inflammation / drug therapy*
  • Inflammation / metabolism
  • Insulin / blood
  • Insulin / metabolism
  • Insulin Resistance
  • Leukocytes / drug effects
  • Leukocytes / metabolism
  • Male
  • NF-kappa B / metabolism
  • Quercetin / pharmacology*
  • Rats
  • Signal Transduction / drug effects
  • Tumor Necrosis Factor-alpha / metabolism
  • Vasoconstriction / drug effects*

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • Blood Glucose
  • Hypoglycemic Agents
  • Insulin
  • NF-kappa B
  • Tumor Necrosis Factor-alpha
  • Collagen
  • C-Reactive Protein
  • Quercetin

Grants and funding

The publication fees and the additional measurements were funded by a research grant ID1024 provided by the Science and Technology Development Fund, Egypt. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.