Aloe-emodin (AE) is an anthraquinone derived from rhubarb and has a variety of pharmacological actions. However, the role of AE in regulating ischemic heart diseases is still unclear. The present study investigated the effect of AE on cardiac injuries induced by myocardial infarction (MI) in vivo and oxidative insults in vitro and explored the mechanisms involved. TUNEL and Flow cytometry were performed to measure cell apoptosis. Western blot analysis was employed to detect expression of Bcl-2, Bax and Caspase-3 proteins. Real-time PCR was used to quantify the microRNAs levels. Our data showed that AE protected neonatal rat ventricular myocytes (NRVMs) from hydrogen peroxide (H2O2) induced apoptosis and significantly inhibited H2O2-induced reactive oxygen species (ROS) elevation. Furthermore, AE treatment significantly reversed H2O2-induced upregulation of Bax/Bcl-2 and the loss of mitochondrial membrane potential. In vivo, AE treatment significantly reduced infarct size, ameliorated impaired cardiac function and obviously decreased cardiac apoptosis and oxidative stress in MI mice heart. Meanwhile, AE restored H2O2-induced downregulation of miR-133, and transfection with miR-133 inhibitor abolished the anti-apoptotic and anti-oxidative effects of AE. Moreover, AE prevented H2O2-induced increase in caspase-3 activity, which was diminished by application of miR-133 inhibitor. Our results indicate that AE protectes against myocardial infarction via the upregulation of miR-133, inhibition of ROS production and suppression of caspase-3 apoptotic signaling pathway.
Keywords: Aloe-emodin; Apoptosis; Caspase-3; MicroRNA-133; Myocardial infarction; Oxidative stress.
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