Hyperoside protects cardiomyocytes against hypoxia-induced injury via upregulation of microRNA-138

Following hypoxia, cardiomyocytes are susceptible to damage, against which microRNA (miR)-138 may act protectively. Hyperoside (Hyp) is a Chinese herbal medicine with multiple biological functions that serve an important role in cardiovascular disease. The aim of the present study was to investigate the role of Hyp in hypoxic cardiomyocytes and its effect on miR-138. A hypoxia model was established in both H9C2 cells and C57BL/6 mice, which were stimulated by Hyp. The expression levels of miR-138 were increased in the hypoxic myocardium in the presence of Hyp at concentrations of >50 µmol/l in vivo and >50 mg/kg in vitro. Using Cell Counting Kit-8 and 5-ethynyl-2′-deoxyuridine assays, it was observed that Hyp improved hypoxia-induced impairment of cell proliferation. Cell apoptosis was evaluated by flow cytometry and a TUNEL assay. The number of apoptotic cells in the Hyp group was lower than that in the control group. As markers of myocardial injury, the levels of lactate dehydrogenase, creatine kinase-myocardial band isoenzyme and malondialdehyde were decreased in the Hyp group compared with the control group, whereas the levels of superoxide dismutase were increased. A marked decrease in the levels of cleaved caspase-3 and cleaved poly(ADP) ribose polymerase and a marked increase in expression levels of Bcl-2 were observed in the presence of Hyp. However, miR-138 inhibition by antagomir attenuated the protective effects of Hyp. Furthermore, Hyp treatment was associated with marked downregulation of mixed lineage kinase 3 and lipocalin-2, but not pyruvate dehydrogenase kinase 1, in hypoxic H9C2 cells. These findings demonstrated that Hyp may be beneficial for myocardial cell survival and may alleviate hypoxic injury via upregulation of miR-138, thereby representing a promising potential strategy for clinical cardioprotection.