Delphinidin attenuates pathological cardiac hypertrophy via the AMPK/NOX/MAPK signaling pathway

Reactive oxygen species (ROS) play a pivotal role in the development of pathological cardiac hypertrophy.Delphinidin, a natural flavonoid, was reported to exert marked antioxidative effects.Therefore, we investigated whether delphinidin ameliorates pathological cardiac hypertrophy via inhibiting oxidative stress.In this study, male C57BL/6 mice were treated with DMSO or delphinidin after surgery.Neonatal rat cardiomyocytes (NRCMs) were treated with angiotensin II (Ang II) and delphinidin in vitro.Eighteen-month-old mice were administered delphinidin to investigate the effect of delphinidin on aging-related cardiac hypertrophy.Through analyses of hypertrophic cardiomyocyte growth, fibrosis and cardiac function, delphinidin was demonstrated to confer resistance to aging-and transverse aortic constriction (TAC)-induced cardiac hypertrophy in vivo and attenuate Ang II-induced cardiomyocyte hypertrophy in vitro by significantly suppressing hypertrophic growth and the deposition of fibrosis.Mechanistically, delphinidin reduced ROS accumulation upon Ang II stimulation through the direct activation of AMP-activated protein kinase (AMPK) and subsequent inhibition of the activity of Rac1 and expression of p47 phox .In addition, excessive levels of ERK1/2, P38 and JNK1/2 phosphorylation induced by oxidative stress were abrogated by delphinidin.Delphinidin was conclusively shown to repress pathological cardiac hypertrophy by modulating oxidative stress through the AMPK/NADPH oxidase (NOX)/mitogen-activated protein kinase (MAPK) signaling pathway.