Document Detail

Molecular mechanisms of cardioprotection by a novel grape seed proanthocyanidin extract.
MedLine Citation:
PMID:  12628506     Owner:  NLM     Status:  MEDLINE    
Free radicals and oxidative stress play a crucial role in the pathophysiology of a broad spectrum of cardiovascular diseases including congestive heart failure, valvular heart disease, cardiomyopathy, hypertrophy, atherosclerosis and ischemic heart disease. We have demonstrated that IH636 grape seed proanthocyanidin extract (GSPE) provides superior antioxidant efficacy as compared to Vitamins C, E and beta-carotene. A series of studies were conducted using GSPE to demonstrate its cardioprotective ability in animals and humans. GSPE supplementation improved cardiac functional assessment including post-ischemic left ventricular function, reduced myocardial infarct size, reduced ventricular fibrillation (VF) and tachycardia, decreased the amount of reactive oxygen species (ROS) as detected by ESR spectroscopy and reduced malondialdehyde (MDA) formation in the heart perfusate. Cardiomyocyte apoptosis detected by terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL) staining. In concert, the proapoptotic signals mediated by JNK-l and c-fos proteins were also reduced suggesting that the novel cardioprotective properties of GSPE may be at least partially attributed to its ability to block anti-death signaling mediated through the proapoptotic transcription factors and genes such as JNK-1 and c-JUN. In a separate study, GSPE pretreatment significantly inhibited doxorubicin-induced cardiotoxicity as demonstrated by reduced serum creatine kinase (CK) activity, DNA damage and histopathological changes in the cardiac tissue of mice. Concentration-dependent efficacy of GSPE was also assessed in a hamster atherosclerosis model. Approximately 49 and 63% reduction in foam cells, a biomarker of early stage atherosclerosis, were observed following supplementation of 50 and 100 mg GSPE/kg body weight, respectively. A human clinical trial was conducted on hypercholesterolemic subjects. GSPE supplementation significantly reduced oxidized LDL, a biomarker of cardiovascular diseases. Finally, a cDNA microarray study demonstrated significant inhibition of inducible endothelial CD36 expression, a novel cardioregulatory gene, by GSPE. These results demonstrate that GSPE may serve as a potential therapeutic tool in promoting cardiovascular health via a number of novel mechanisms.
Debasis Bagchi; Chandan K Sen; Sidhartha D Ray; Dipak K Das; Manashi Bagchi; Harry G Preuss; Joe A Vinson
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Mutation research     Volume:  523-524     ISSN:  0027-5107     ISO Abbreviation:  Mutat. Res.     Publication Date:    2003 Feb-Mar
Date Detail:
Created Date:  2003-03-11     Completed Date:  2003-04-24     Revised Date:  2005-11-16    
Medline Journal Info:
Nlm Unique ID:  0400763     Medline TA:  Mutat Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  87-97     Citation Subset:  IM    
Copyright Information:
Copyright 2003 Elsevier Science B.V.
Department of Pharmacy Sciences, Medical Center, School of Pharmacy and Creighton University Health Professions, 2500 California Plaza, Omaha, NE 68178, USA.
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MeSH Terms
Anthocyanins / isolation & purification*,  pharmacology
Antioxidants / isolation & purification*,  pharmacology
Arteriosclerosis / prevention & control
Cardiotonic Agents / chemistry,  isolation & purification,  pharmacology*
Doxorubicin / toxicity
Free Radical Scavengers
Heart / drug effects
Hypercholesterolemia / drug therapy
Mice, Inbred ICR
Myocardium / pathology
Plant Extracts / isolation & purification,  pharmacology*
Reg. No./Substance:
0/Anthocyanins; 0/Antioxidants; 0/Cardiotonic Agents; 0/Free Radical Scavengers; 0/Plant Extracts; 0/Proanthocyanidins; 18206-61-6/proanthocyanidin; 23214-92-8/Doxorubicin

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