title: The effect of angoroside C on pressure overload-induced ventricular remodeling in rats.
abstract: BACKGROUND
  Our previous study reveals that total rough extract of Radix Scrophulariae has a beneficial effect on ventricular remodeling.
  
  
  OBJECTIVE
  After carrying out a series of preliminary experiments, we speculated that angoroside C may be the effective agent.
  
  
  METHODS
  After oral administration, the effect of angoroside C on ventricular remodeling was evaluated by using a pressure-overloaded rat model, some related indexes were detected in vivo.
  
  
  METHODS
  A model of pressure overloaded ventricular remodeling was produced by abdominal aortic constriction (AAC) in rats. The sham-operated rats underwent an identical surgical procedure except for AAC. AAC rats were randomly divided into five groups: model control group, three angoroside C treated groups (7.5, 15 and 30 mg·kg(-1)) and captopril treated group (40 mg·kg(-1)). The rats were orally administered with the corresponding drugs or drinking water for 4 weeks. The levels of blood pressure (BP), left ventricular weight index (LVWI) and heart weight index (HWI) were detected. Myocardium tissue was stained with hematoxylin and eosin or picric acid/sirius red for cardiomyocyte cross-section area or collagen content measurements respectively. The concentrations of angiotensin Ⅱ (Ang Ⅱ), hydroxyproline (Hyp), matrix metalloproteinase 2 (MMP-2), MMP-9 and tissue inhibitor of metalloproteinase-1 (TIMP-1) in myocardium or serum were determined. Real-time RT-PCR was performed to detect the mRNA expressions of endothelin 1 (ET-1), transforming growth factor β1 (TGF-β1).
  
  
  RESULTS
  Angoroside C significantly reduced the BP, LVWI and HWI, decreased the content of Ang Ⅱ, Hyp, diminished cross sectional area of cardiomyocytes and ameliorated collagen deposition. Additionally, it markedly reduced collagen I and III expressions and regulated matrix metalloproteinase-2, 9 and inhibitors of metalloproteinase expressions. Angoroside C also down regulated the gene expressions of ET-1 and TGF-β1mRNA in myocardium.
  
  
  CONCLUSIONS
  Angoroside C has beneficial effects against ventricular remodeling. The mechanism is likely to be related to decreasing the level of Ang Ⅱ, attenuating the mRNA expressions of ET-1 and TGF-β1.
authors.affiliation: Department of Pharmacology, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201203, China.
authors.forename: Wei Liang
authors.initials: WL
authors.lastname: Gu
authors.affiliation: Department of Pharmacology, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201203, China. Electronic address: cxchen6@126.com.
authors.forename: Chang Xun
authors.initials: CX
authors.lastname: Chen
authors.affiliation: Department of Pharmacology, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201203, China.
authors.forename: Xiao Yan
authors.initials: XY
authors.lastname: Huang
authors.affiliation: Department of Pharmacology, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201203, China.
authors.forename: Jian Ping
authors.initials: JP
authors.lastname: Gao
mesh_terms: D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000473:pathology; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology; D003094:Collagen / Q000378:metabolism; D003251:Constriction, Pathologic; D003373:Coumaric Acids / Q000494:pharmacology*; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D006909:Hydroxyproline / Q000378:metabolism; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D032266:Scrophularia / Q000737:chemistry; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014312:Trisaccharides / Q000494:pharmacology*; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: D003373:Coumaric Acids; D019332:Endothelin-1; C576839:TIMP1 protein, rat; C508962:Tgfb1 protein, rat; D019715:Tissue Inhibitor of Metalloproteinase-1; D053773:Transforming Growth Factor beta1; D014312:Trisaccharides; D000804:Angiotensin II; C413578:angoroside C; D003094:Collagen; D002216:Captopril; D020778:Matrix Metalloproteinase 2; C522363:Mmp2 protein, rat; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat; D006909:Hydroxyproline
keywords: Abdominal aortic constriction; Angoroside C; Rat; Ventricular remodeling