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

Aging (Albany NY). 2020 Mar 25;12(6):5362-5383. doi: 10.18632/aging.102956. Epub 2020 Mar 25.


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 p47phox. 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.

Keywords: AMPK; NADPH oxidase; cardiac hypertrophy; delphinidin; oxidative stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases / metabolism*
  • Angiotensin II / pharmacology
  • Animals
  • Anthocyanins / pharmacology*
  • Cardiomegaly / metabolism*
  • Fibrosis / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Myocytes, Cardiac / metabolism
  • NADPH Oxidases / metabolism
  • Oxidative Stress
  • Phosphorylation
  • Rats
  • Reactive Oxygen Species / metabolism
  • Signal Transduction
  • p38 Mitogen-Activated Protein Kinases / metabolism


  • Anthocyanins
  • Reactive Oxygen Species
  • Angiotensin II
  • NADPH Oxidases
  • p38 Mitogen-Activated Protein Kinases
  • AMP-Activated Protein Kinases
  • delphinidin