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J Nutr Biochem. 2018 Dec;62:221-229. doi: 10.1016/j.jnutbio.2018.08.010. Epub 2018 Sep 1.

Fisetin inhibits cardiac hypertrophy by suppressing oxidative stress.

Author information

1
Department of Cardiology, Heart Center, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China, 510080; NHC Key Laboratory of Assisted Circulation (Sun Yat-sen University), Guangzhou, China, 510080.
2
Animal Research Center, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China, 510080.
3
Department of Cardiology, Heart Center, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China, 510080; NHC Key Laboratory of Assisted Circulation (Sun Yat-sen University), Guangzhou, China, 510080. Electronic address: dongxg@mail.sysu.edu.cn.
4
Department of Cardiology, Heart Center, the First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China, 510080; NHC Key Laboratory of Assisted Circulation (Sun Yat-sen University), Guangzhou, China, 510080. Electronic address: hhl127@163.com.

Abstract

Cardiac hypertrophy is a pathophysiological response to various pathological stresses and ultimately leads to heart failure. Oxidative stress is one of the critical processes involved in hypertrophy development. Fisetin, a small molecular flavonoid, has been shown to have anti-oxidative, anti-proliferative and anti-inflammatory properties. However, the effect of fisetin on cardiac hypertrophy remains unknown. In our present study, we showed that fisetin inhibited pressure overload-induced cardiac hypertrophy, improved cardiac function in vivo and suppressed phenylephrine (PE)-induced cardiomyocyte hypertrophy in vitro. Reactive oxygen species (ROS) levels were markedly decreased by fisetin treatment in both hypertrophic hearts and cardiomyocytes. Moreover, fisetin significantly up-regulated the expression of antioxidative genes, including catalase (CAT), superoxide dismutase 1 (SOD1) and heme oxygenase 1 (HO-1). Furthermore, co-treatment with N-acetylcysteine (NAC; ROS scavenger) and fisetin did not have synergistic inhibitory effects on PE-induced cardiomyocyte hypertrophy, indicating that the anti-hypertrophic effects of fisetin are mainly associated with the blockade of oxidative stress. Finally, the pro-hypertrophic signaling pathways, mitogen-activated protein kinase (MAPK) and mammalian target of rapamycin (mTOR) kinase, were found to be suppressed by fisetin after pressure overload and PE treatment. In conclusion, our study revealed that fisetin protects against cardiac hypertrophy and that oxidative stress inhibition may be one of the pivotal mechanisms involved.

KEYWORDS:

Cardiac hypertrophy; Fisetin; Heart failure; Oxidative stress; Reactive oxygen species

PMID:
30312797
DOI:
10.1016/j.jnutbio.2018.08.010
[Indexed for MEDLINE]

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