Safranal alleviates pressure overload induced-cardiac hypertrophy and dysfunction via activating AMPK signaling pathway

Abstract

Objective: The study investigated the effect and mechanism of Safranal (SFR) on cardiac hypertrophy and dysfunction during pressure overload. Methods: Cardiac hypertrophy model of pressure overload was established firstly. Then, experiment was divided into Sham (sham surgery), AB (abdominal aortic coarctation surgery), AB+SFR1 (treated with 1 mg/kg SFR), AB+SFR2 (treated with 2 mg/kg SFR), AB+SFR4 (treated with 4 mg/kg SFR) groups. Cardiac function was detected by Echocardiography and cardiac morphology and myocardial fiber diameter were detected via HE staining. Myocardial hypertrophy markers -ANP, BNP, apoptosis factors -Capase-3, Capase-9, and inflammatory factors- IL-1β, TNFα were detected by Western blot and Polymerase Chain Reaction (PCR). To further investigate the relevant mechanism, the study was divided into Sham, AB, AB+SFR, AB+SFR+CPD (treated with AMPK inhibitor -compound C and 2 mg/kg SFR). Afterwards, the myocardial hypertrophy, cardiac function, and AMPK signaling pathway-related molecules AMPK, ACC were detected respectively. Results: In 1, 2, and 4 mg/kg SFR treatment groups, the degree of myocardial hypertrophy mitigated, and cardiac dysfunction improved compared with AB group. Simultaneously, the myocardial apoptosis and inflammation reduced, AMPK signaling pathway-related molecules AMPK and ACC increased. When AMPK signaling pathway was inhibited, the myocardial hypertrophy and cardiac dysfunction aggravated in AB+SFR+CPD group compared with the AB+SFR group, so does the myocardial inflammation and apoptosis. Namely, inhibition of AMPK signaling pathway reversed the protective effect of SFR on the cardiac hypertrophy. Conclusions: SFR alleviated pressure overload induced-cardiac hypertrophy and dysfunction via activating AMPK signaling pathway.