Acacetin ameliorates cardiac hypertrophy by activating Sirt1/AMPK/PGC-1α pathway

Cardiac hypertrophy is a major risk factor for developing heart failure. This study investigates the effects of the natural flavone acacetin on myocardial hypertrophy in cellular level and whole animals. In cardiomyocytes from neonatal rat with hypertrophy induced by angiotensin II (Ang II), acaceti...

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Published in:European journal of pharmacology 2022-04, Vol.920, p.174858-174858, Article 174858
Main Authors: Cui, Yu-Kai, Hong, Yi-Xiang, Wu, Wei-Yin, Han, Wei-Min, Wu, Yao, Wu, Chan, Li, Gui-Rong, Wang, Yan
Format: Article
Language:English
Subjects:
AMP-Activated Protein Kinases - metabolism
AMPK
Angiotensin
Animals
Cardiac hypertrophy
Cardiomegaly - metabolism
Flavones
Myocytes, Cardiac
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha - metabolism
PGC-1α
Rats
Rats, Sprague-Dawley
Sirt1
Sirtuin 1 - metabolism
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Summary:Cardiac hypertrophy is a major risk factor for developing heart failure. This study investigates the effects of the natural flavone acacetin on myocardial hypertrophy in cellular level and whole animals. In cardiomyocytes from neonatal rat with hypertrophy induced by angiotensin II (Ang II), acacetin at 0.3, 1, and 3 μM reduced the increased myocyte surface area, brain natriuretic peptide (BNP), and ROS production by upregulating anti-oxidative molecules (i.e. Nrf2, SOD1, SOD2, HO-1), anti-apoptotic protein Bcl-2, and downregulating the pro-apoptotic protein Bax and the inflammatory cytokine IL-6 in a concentration-dependent manner. In addition, acacetin rescued Ang II-induced impairment of PGC-1α, PPARα and pAMPK. These beneficial effects of acacetin were mediated by activation of Sirt1, which was confirmed in cardiac hypertrophy induced by abdominal aorta constriction (AAC) in SD rats. Acacetin prodrug (10 mg/kg, s.c., b.i.d.) treatment reduced the elevated artery blood pressure, improved the increased heart size and thickness of left ventricular wall and the ventricular fibrosis associated with inhibiting myocardial fibrosis and BNP, and reversed the impaired protective signal molecules including PGC-1α, Nrf2, PPARα, pAMPK and Sirt1 of left ventricular tissue. Our results demonstrate the novel pharmacological effect that acacetin ameliorates cardiac hypertrophy via Sirt1-mediated activation of AMPK/PGC-1α signal molecules followed by reducing oxidation, inflammation and apoptosis.
ISSN:0014-2999
1879-0712
DOI:10.1016/j.ejphar.2022.174858