Naringenin Protects Rats against Ang-II Induced Cardiac Hypertrophy and Fibrosis by Downregulating TGF-β1/Smads Signaling Pathways

Abstract Background:Naringenin (Nrg), a flavone found in several plant foods with various biological properties, has been shown prevention of cardiac remodeling. However, themechanisms underlying this suppression of cardiac remodeling has not been known clearly.Methods: Male Sprague Dawley (SD) rats were AngII infused via osmotic minipumps for 4 weeks and were given Nrg by gavage (100mg/kg/day) at the same time. In vitro experiments used cardiomyocyte and cardiac fibroblasts(CF) treated with AngII or AngII plus Nrg.Cardiac remodeling was assessed using the echocardiography and histological analysis. And, the effect of Nrg on TGF-β1/Smadssignaling pathway was investigated.Results: Treatmentwith Nrg(100mg/kg/day) decreased the ratio of heart weight to tibia length and hypertrophy markers in rats given AngII infusion. In vitro experiments demonstrated that AngII-induced cardiomyocyte hypertrophy and proliferation of CFs were significantly inhibited by Nrg administration. Nrg inhibited activation of the TGF-β1/Smad2/3 signaling pathway stimulated by AngII. Conclusions: Nrgsupplementation prevented cardiac remodeling via down-regulating the TGF-β1/Smad2/3 signaling pathway both in cardiomyocyte and CFs, and attenuating cardiac remodeling in AngII-induced rats model.