Propolis, a traditional medicine, has been widely used for a thousand years as an anti-inflammatory and antioxidant drug. The flavonoid fraction is the main active component of propolis, which possesses a wide range of biological activities, including activities related to heart disease. However, the role of the flavonoids extraction from propolis (FP) in heart disease remains unknown. This study shows that FP could attenuate ISO-induced pathological cardiac hypertrophy (PCH) and heart failure in mice. The effect of the two fetal cardiac genes, atrial natriuretic factor (ANF) and β-myosin heavy chain (β-MHC), on PCH was reversed by FP. Echocardiography analysis revealed cardiac ventricular dilation and contractile dysfunction in ISO-treated mice. This finding is consistent with the increased heart weight and cardiac ANF protein levels, massive replacement fibrosis, and myocardial apoptosis. However, pretreatment of mice with FP could attenuate cardiac dysfunction and hypertrophy in vivo. Furthermore, the cardiac protection of FP was suppressed by the pan-PI3K inhibitor wortmannin. FP is a novel cardioprotective agent that can attenuate adverse cardiac dysfunction, hypertrophy, and associated disorder, such as fibrosis. The effects may be closely correlated with PI3K/AKT signaling. FP may be clinically used to inhibit PCH progression and heart failure.

The flavonoid extract from propolis (FP) has been shown to protect against heart injury induced by isoproterenol. However, the effect of FP on cardiac fibrosis after myocardial infarction (MI) as well as the underlying mechanisms is not known. In the present study, we used biochemical and histological approaches to examine the effects of FP on MI-induced cardiac fibrosis and the related mechanisms in a rat MI model and in angiotensin II- (Ang II-) treated rat cardiac fibroblasts (CFs). In vivo, MI was generated by ligation of the left anterior descending coronary artery of rats, which remained for 4 weeks. Rats were randomly divided into the sham, MI, FP (12.5 mg/kg/d), and MI+FP groups. We found that FP treatment improved heart function, reduced cardiac fibrosis, and downregulated the expression of fibrosis-related factors including collagen I, collagen III, matrix metalloproteinase-2 (MMP-2), MMP-9, transforming growth factor-β1 (TGF-β1), and p-Smad2/3, which coincided with the upregulated expression of silent information regulator 1 (SIRT1) in the hearts of MI rats. Our in vitro experiments showed that FP inhibited the proliferation and migration of primary cultured rat CFs and downregulated the expression of the above-mentioned fibrosis-related factors in Ang II-stimulated CFs. In addition, FP can decrease ROS production induced by MI and Ang II in vivo and vitro. Notably, silencing SIRT1 counteracted the FP-induced effects on CFs treated with Ang II. We conclude that FP inhibits MI-induced cardiac fibrosis through SIRT1 activation and that FP represents a potential promising drug for the treatment of MI patients in the clinic.