Icariin inhibits isoproterenol-induced cardiomyocyte hypertropic injury through activating autophagy via the AMPK/mTOR signaling pathway

Abstract

Icariin (ICA), a bioactive flavonoid compound derived from Epimedium, have been demonstrated possessing anti-oxidative stress, anti-inflammation in the cardiovascular disease. But its effects on cardiomyocyte hypertrophy and the underlying mechanisms remains unclear. Here we found that ICA alleviated ISO-induced H9c2 or NRCM myocytes hypertrophy, assessed by surface area and the expression of ANP, BNP and β-MHC. Furthemore, ICA reversed cardiomcytes enlargment by suppresing apoptotic injury and increasing autophagic flux. By contrast, 3-MA, an autophagy inhibitor, could abolished the antihypertrophic and pro-autophagic flux effects of ICA. Mechanistically, ICA increased the phosphorylation levels of AMPK and autophagy-related markers beclin-1, Atg5 and the LC3II/I ratio, and decreased phosphorylated mTOR. But the effects of ICA on ISO-induced cardiomyocytes hypertrophy were attenuated by selective AMPK inhibitor Compound C. In conclusion, these findings indicated that ICA attenuated cardiomyocyte hypertrophy induced by ISO and prevented cell injury, and the specific mechanism was mediated by AMPK/mTOR pathway to enhance autophagy and reduce autophagy-related cardiomyocyte apoptosis.