Zerumbone prevents pressure overload-induced left ventricular systolic dysfunction by inhibiting cardiac hypertrophy and fibrosis.

Abstract

BACKGROUND:

Cardiac hypertrophy and fibrosis are hallmarks of cardiac remodeling and are involved functionally in the development of heart failure (HF). However, it is unknown whether Zerumbone (Zer) prevents left ventricular (LV) systolic dysfunction by inhibiting cardiac hypertrophy and fibrosis.

PURPOSE:

This study investigated the effect of Zer on cardiac hypertrophy and fibrosis in vitro and in vivo.

STUDY DESIGN/METHODS:

In primary cultured cardiac cells from neonatal rats, the effect of Zer on phenylephrine (PE)-induced hypertrophic responses and transforming growth factor beta (TGF-β)-induced fibrotic responses was observed. To determine whether Zer prevents the development of pressure overload-induced HF in vivo, a transverse aortic constriction (TAC) mouse model was utilized. Cardiac function was evaluated by echocardiography. The changes of cardiomyocyte surface area were observed using immunofluorescence staining and histological analysis (HE and WGA staining). Collagen synthesis and fibrosis formation were measured by scintillation counter and picrosirius staining, respectively. The total mRNA levels of genes associated with hypertrophy (ANF and BNP) and fibrosis (Postn and α-SMA) were measured by qRT-PCR. The protein expressions (Akt and α-SMA) were assessed by western blotting.

RESULTS:

Zer significantly suppressed PE-induced increase in cell size, mRNA levels of ANF and BNP, and Akt phosphorylation in cardiomyocytes. The TGF-β-induced increase in proline incorporation, mRNA levels of Postn and α-SMA, and protein expression of α-SMA were decreased by Zer in cultured cardiac fibroblasts. In the TAC male C57BL/6 mice, echocardiography results demonstrated that Zer improved cardiac function by increasing LV fractional shortening and reducing LV wall thickness compared with the vehicle group. ZER significantly reduced the level of phosphorylated Akt both in cultured cardiomyocytes treated with PE and in the hearts of TAC. Finally, Zer inhibited the pressure overload-induced cardiac hypertrophy and cardiac fibrosis.

CONCLUSION:

Zer ameliorates pressure overload-induced LV dysfunction, at least in part by suppressing both cardiac hypertrophy and fibrosis.

• Authors: Nurmila Sari, Yasufumi Katanasaka, Yuga Sugiyama, Yoichi Sunagawa, Yusuke Miyazaki, Masafumi Funamoto, Satoshi Shimizu, Kana Shimizu, Akira Murakami, Kiyoshi Mori, Hiromichi Wada, Koji Hasegawa, Tatsuya Morimoto
• Journal: Phytomedicine : international journal of phytotherapy and phytopharmacology (Phytomedicine) Vol. 92 Pg. 153744 (Nov 2021) ISSN: 1618-095X [Electronic] Germany
• PMID: 34563985 (Publication Type: Journal Article)
• Copyright: Copyright © 2021. Published by Elsevier GmbH.

Chemical References

• Sesquiterpenes
• zerumbone

Topics

• Animals
• Cardiomegaly (drug therapy, pathology)
• Fibrosis
• Male
• Mice
• Mice, Inbred C57BL
• Myocardium (pathology)
• Myocytes, Cardiac (pathology)
• Rats
• Sesquiterpenes
• Ventricular Remodeling