The effect of angoroside C on pressure overload-induced ventricular remodeling in rats

Background: Our previous study reveals that total rough extract of Radix Scrophulariae has a beneficial effect on ventricular remodeling. Hypothesis: After carrying out a series of preliminary experiments, we speculated that angoroside C may be the effective agent. Study design: 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. MC 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 acidisirius 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 beta 1 (TGF-beta 1). 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-beta 1mRNA in myocardium. Conclusion: 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-beta 1. (C) 2015 Elsevier GmbH. All rights reserved.