Geniposide alleviates pressure overload in cardiac fibrosis with suppressed TGF-β1 pathway

Background: Cardiac fibrosis is one of the main contributors to the pathogenesis of heart failure. Geniposide (GE), a major iridoid in gardenia fruit extract, has recently been reported to improve skeletal muscle fibrosis through the modulation of inflammation response. This investigation aimed to illuminate the cardio-protective effect and the potential mechanism of GE in cardiac fibrosis. Material and methods: A transverse aortic contraction (TAC) induction mice model was established and GE (0 mg/ kg; 10 mg/kg; 20 mg/kg; 40 mg/kg) was administered by oral gavage daily for 4 weeks. Hemodynamic pa-rameters, Masson's trichrome stain, and hematoxylin-eosin (HE) staining were estimated and cardiomyocyte fibrosis, interstitial collagen levels, and hypertrophic markers were analyzed using qPCR and western blot. In vitro, H9C2 cells were exposed to the Ang II (1 mu M) pretreated with GE (0.1 mu M, 1 mu M, and 10 mu M). Car-diomyocyte apoptosis was detected. Moreover, the transforming growth factor beta 1 (TGF-beta 1)/Smad2 pathway was assessed in vivo and in vitro. Results: GE significantly ameliorated TAC-induced cardiac hypertrophy, ventricular remodeling, myocardial fibrosis, and improved cardiac function in vivo, and it inhibited Ang II-induced cardiomyocyte apoptosis in vitro. We further observed that the inflammatory channel TGF-beta 1/Smad2 pathway was suppressed by GE both in vivo and in vitro. Conclusion: These results indicate that GE inhibited myocardial fibrosis and improved hypertrophic car-diomyocytes with attenuated the TGF-beta 1/Smad2 pathway and proposed to be an important therapeutic of car-diac fibrosis reduced by TAC.