title: Ginseng reverses established cardiomyocyte hypertrophy and postmyocardial infarction-induced hypertrophy and heart failure.
abstract: BACKGROUND
  A major challenge in the treatment of heart failure is the ability to reverse already-established myocardial remodeling and ventricular dysfunction, with few available pharmacological agents prescribed for the management of heart failure having demonstrated successful reversal of the remodeling and hypertrophic processes. North American ginseng (Panax quinquefolius) has previously been shown to effectively prevent cardiomyocyte hypertrophy and heart failure. Here, we determined whether North American ginseng can reverse established cardiomyocyte hypertrophy in cultured myocytes as well as hypertrophy and left ventricular dysfunction in experimental heart failure secondary to coronary artery occlusion.
  
  
  RESULTS
  Ginseng was administered in drinking water (0.9 g/L) ad libitum to rats after 4 weeks of sustained coronary artery ligation when heart failure was established or to angiotensin II- (100 nmol/L), endothelin-1- (10 nmol/L), or phenylephrine- (10 µmol/L) induced hypertrophic cultured neonatal ventricular cardiomyocytes. Echocardiographic and catheter-based measurements of hemodynamic parameters 4 weeks after starting ginseng treatment (8 weeks postinfarction) revealed nearly complete reversibility of systolic and diastolic abnormalities. Similarly, ginseng administration to hypertrophic cardiomyocytes resulted in a complete reversal to a normal phenotype after 24 hours as determined by cell surface area and expression of molecular markers. The effects of ginseng both in vivo and in cultured cardiomyocytes were associated with reversal of calcineurin activation and reduced nuclear translocation of the transcription factor NFAT3 (nuclear factor of activated T cells 3) in cultured myocytes. Moreover, the beneficial effect of ginseng was associated with normalization in the gene expression of profibrotic markers, including collagen (I and III) and fibronectin.
  
  
  CONCLUSIONS
  This study demonstrates a marked ability of ginseng to reverse cardiac hypertrophy, myocardial remodeling, and heart failure, which was associated with and likely mediated by reversal of calcineurin activation. Ginseng may offer a potentially effective approach to reverse the myocardial remodeling and heart failure processes, particularly in combination with other treatment modalities.
authors.affiliation: Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, The University of Western Ontario, London, ON, Canada.
authors.forename: Melissa
authors.initials: M
authors.lastname: Moey
authors.forename: Xiaohong T
authors.initials: XT
authors.lastname: Gan
authors.forename: Cathy Xiaoling
authors.initials: CX
authors.lastname: Huang
authors.forename: Venkatesh
authors.initials: V
authors.lastname: Rajapurohitam
authors.forename: Eduardo
authors.initials: E
authors.lastname: Martínez-Abundis
authors.forename: Edmund M K
authors.initials: EM
authors.lastname: Lui
authors.forename: Morris
authors.initials: M
authors.lastname: Karmazyn
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D019703:Calcineurin / Q000378:metabolism; D006332:Cardiomegaly / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D006333:Heart Failure / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009203:Myocardial Infarction / Q000150:complications* / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D050778:NFATC Transcription Factors / Q000378:metabolism; D005894:Panax; D028321:Plant Preparations / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014463:Ultrasonography; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D016277:Ventricular Function, Left / Q000187:drug effects; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: D002316:Cardiotonic Agents; D050778:NFATC Transcription Factors; D028321:Plant Preparations; D019703:Calcineurin