Rosmarinic acid administration attenuates diabetes-induced vascular dysfunction of the rat aorta

J Pharm Pharmacol. 2013 May;65(5):713-23. doi: 10.1111/jphp.12037. Epub 2013 Feb 27.

Abstract

Objectives: Oxidative stress as well as inflammation processes are engaged in diabetic vascular complications. Rosmarinic acid, a natural phenol antioxidant carboxylic acid, was found to have multiple biological activity, including anti-inflammatory and antitumour effects, which are a consequence of its inhibition of the inflammatory processes and of reactive oxygen species scavenging. The aim of this work was to study effects of rosmarinic acid administration on vascular impairment induced by experimental diabetes in rats.

Methods: Diabetes was induced by streptozocin (3 × 30 mg/kg daily, i.p.) in Wistar rats. Rosmarinic acid was administered orally (50 mg/kg daily). Ten weeks after streptozocin administration, the aorta was excised for functional studies, evaluation by electron microscopy and real time PCR analysis.

Key findings: In the aorta of diabetic rats, decreased endothelium-dependent relaxation was accompanied by overexpression of interleukin-1β, tumour necrosis factor-α, preproendothelin-1 and endothelin converting enzyme-1. Structural alterations in the endothelium, detected by electron microscopy, indicated aortic dysfunction caused by diabetes. The diabetes-induced aortic disorders were prevented by rosmarinic acid administration.

Conclusions: Rosmarinic acid protected aortic endothelial function and ultrastructure against diabetes-induced damage. Both antioxidant and anti-inflammatory effects of rosmarinic acid seemed to participate in the mechanism of this protection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use*
  • Aorta / drug effects*
  • Aorta / pathology
  • Aorta / physiopathology
  • Aspartic Acid Endopeptidases / metabolism
  • Cinnamates / pharmacology
  • Cinnamates / therapeutic use*
  • Depsides / pharmacology
  • Depsides / therapeutic use*
  • Diabetes Complications / metabolism
  • Diabetes Complications / pathology
  • Diabetes Complications / physiopathology
  • Diabetes Complications / prevention & control
  • Diabetes Mellitus, Experimental / complications
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / pathology
  • Diabetes Mellitus, Experimental / physiopathology
  • Endothelin-1 / metabolism
  • Endothelin-Converting Enzymes
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / pathology
  • Endothelium, Vascular / physiopathology
  • Interleukin-1beta / metabolism
  • Lamiaceae / chemistry*
  • Male
  • Metalloendopeptidases / metabolism
  • Phytotherapy
  • Rats
  • Rats, Wistar
  • Rosmarinic Acid
  • Tumor Necrosis Factor-alpha / metabolism
  • Vascular Diseases / metabolism
  • Vascular Diseases / pathology
  • Vascular Diseases / physiopathology
  • Vascular Diseases / prevention & control*
  • Vasodilation / drug effects

Substances

  • Antioxidants
  • Cinnamates
  • Depsides
  • Endothelin-1
  • Interleukin-1beta
  • Tumor Necrosis Factor-alpha
  • Aspartic Acid Endopeptidases
  • Metalloendopeptidases
  • Endothelin-Converting Enzymes