Cirsimaritin Ameliorates Cardiac Remodeling And Dysfunction Through Promoting Myocardial Autophagy In Rats With Heart Failure

Cirsimaritin, a natural flavone, has been reported to exert various activities including antibacterial, anti-inflammation, anti-tumor, antioxidant, renal protection and so on. However, despite these pharmacological studies, whether cirsimaritin alleviates heart failure is still unknown. Administration of isoproterenol led to a serious heart failure, as evidenced by the up-regulation of heart rate, weight index and end diastolic pressure of left ventricular, while by the down-regulation of left ventricular systolic pressure, maximal rate of pressure rise or decline of left ventricular. Pretreatment of cirsimaritin significantly ameliorated these cardiac parameters in a dose-dependent manner. In addition, cirsimaritin remarkably inhibited serum levels of Ang II, NE, TNF-alpha and BNP in rats with heart failure and attenuated the cardiac histological changes. Moreover, matrix metalloproteinase-2&9 activities were also suppressed by cirsimaritin. Furthermore, myocardial autophagy was significantly promoted by cirsimaritin in vivo and in vitro through inhibiting AKT1-RPS6KB1 signaling. These findings reveal that cirsimaritin mitigates cardiac remodeling and left ventricular dysfunction through augmenting myocardial autophagy and decreasing matrix metalloproteinase-2&9 activities, suggesting its potential use in patients with congestive heart failure.