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

Abstract

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.

• Authors: Youming Chen, Zhuowang Ge, Shixing Huang, Lei Zhou, Changlin Zhai, Yuhan Chen, Qiuyue Hu, Wei Cao, Yuteng Weng, Yanyan Li
• Journal: Aging (Aging (Albany NY)) Vol. 12 Issue 6 Pg. 5362-5383 (03 25 2020) ISSN: 1945-4589 [Electronic] United States
• PMID: 32209725 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• 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)