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Administration of rosmarinic acid reduces cardiopathology and blood pressure through inhibition of p22phox NADPH oxidase in fructose-fed hypertensive rats.

Abstract
Rosmarinic acid (RA), a caffeic acid ester, has insulin-sensitizing and antioxidant effects in high fructose-fed model of insulin resistance (IR). This study investigated whether RA supplementation prevents cardiac abnormalities and hypertension in fructose-fed rats (FFR). Rats fed with fructose diet (60 g/100 g) for 60 days exhibited metabolic abnormalities and rise in plasma and cardiac lipids and whole body IR. The levels of cardiac antioxidants and plasma ferric reducing antioxidant power were significantly reduced in FFR concomitant with increased levels of lipid peroxidation and protein oxidation products. A significant rise in troponin T, creatine kinase-MB, aspartate transaminase, and lactate dehydrogenase in plasma of FFR was noted. RA supplementation to FFR (10 mg/kg from the 16th day) significantly improved insulin sensitivity, reduced lipid levels, oxidative damage, and the expression of p22phox subunit of nicotinamide adenine dinucleotide phosphate reduced oxidase, and prevented cardiac hypertrophy. Fructose-induced rise in blood pressure was also lowered by RA through decrease in endothelin-1 and angiotensin-converting enzyme activity and increase in nitric oxide levels. Histology revealed a reduction in myocardial damage in RA-supplemented FFR. These findings suggest that RA acts as a vasoactive substance and a cardioprotector through its antioxidant property. Thus, RA may be useful in reducing the cardiovascular risk associated with IR.
AuthorsDhanapalan Karthik, Periyasami Viswanathan, Carani Venkatraman Anuradha
JournalJournal of cardiovascular pharmacology (J Cardiovasc Pharmacol) Vol. 58 Issue 5 Pg. 514-21 (Nov 2011) ISSN: 1533-4023 [Electronic] United States
PMID21795992 (Publication Type: Journal Article)
Chemical References
  • Antioxidants
  • Blood Glucose
  • Cinnamates
  • Depsides
  • Dietary Carbohydrates
  • Endothelin-1
  • Insulin
  • Lipids
  • Nitrates
  • Troponin C
  • Fructose
  • L-Lactate Dehydrogenase
  • Nitric Oxide Synthase Type III
  • Nos3 protein, rat
  • NADPH Oxidases
  • Cyba protein, rat
  • Aspartate Aminotransferases
  • Creatine Kinase, MB Form
  • Peptidyl-Dipeptidase A
  • Kallikreins
  • rosmarinic acid
Topics
  • Animals
  • Antioxidants (metabolism)
  • Aspartate Aminotransferases (blood)
  • Blood Glucose (drug effects)
  • Blood Pressure (drug effects, physiology)
  • Body Weight (drug effects)
  • Cinnamates (pharmacology, therapeutic use)
  • Creatine Kinase, MB Form (blood)
  • Depsides (pharmacology, therapeutic use)
  • Dietary Carbohydrates (pharmacology)
  • Endothelin-1 (metabolism)
  • Fructose (administration & dosage, pharmacology)
  • Gene Expression (drug effects)
  • Heart (drug effects)
  • Hyperinsulinism (blood, prevention & control)
  • Hypertension (etiology, physiopathology, prevention & control)
  • Insulin (blood)
  • Insulin Resistance (physiology)
  • Kallikreins (blood)
  • L-Lactate Dehydrogenase (blood)
  • Lipid Metabolism (drug effects)
  • Lipids (blood)
  • Male
  • Myocardium (metabolism, pathology)
  • NADPH Oxidases (metabolism)
  • Nitrates (blood)
  • Nitric Oxide Synthase Type III (metabolism)
  • Organ Size (drug effects)
  • Oxidative Stress (drug effects)
  • Peptidyl-Dipeptidase A (blood)
  • Rats
  • Rats, Wistar
  • Troponin C (blood)

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