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Planta Med 2020; 86(17): 1304-1312
DOI: 10.1055/a-1191-7970
Biological and Pharmacological Activity
Original Papers

Cacao Bean Polyphenols Inhibit Cardiac Hypertrophy and Systolic Dysfunction in Pressure Overload-induced Heart Failure Model Mice

Nurmila Sari
1   Division of Molecular Medicine, Graduate School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan
,
Yasufumi Katanasaka
1   Division of Molecular Medicine, Graduate School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan
2   Clinical Research Institute, National Hospital Organization Kyoto Medical Center, Kyoto, Japan
3   Shizuoka General Hospital, Shizuoka, Japan
,
Hiroki Honda
1   Division of Molecular Medicine, Graduate School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan
,
Yusuke Miyazaki
1   Division of Molecular Medicine, Graduate School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan
2   Clinical Research Institute, National Hospital Organization Kyoto Medical Center, Kyoto, Japan
3   Shizuoka General Hospital, Shizuoka, Japan
,
Yoichi Sunagawa
1   Division of Molecular Medicine, Graduate School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan
2   Clinical Research Institute, National Hospital Organization Kyoto Medical Center, Kyoto, Japan
3   Shizuoka General Hospital, Shizuoka, Japan
,
Masafumi Funamoto
1   Division of Molecular Medicine, Graduate School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan
2   Clinical Research Institute, National Hospital Organization Kyoto Medical Center, Kyoto, Japan
,
Kana Shimizu
1   Division of Molecular Medicine, Graduate School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan
2   Clinical Research Institute, National Hospital Organization Kyoto Medical Center, Kyoto, Japan
,
Satoshi Shimizu
1   Division of Molecular Medicine, Graduate School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan
2   Clinical Research Institute, National Hospital Organization Kyoto Medical Center, Kyoto, Japan
,
Hiromichi Wada
2   Clinical Research Institute, National Hospital Organization Kyoto Medical Center, Kyoto, Japan
,
Koji Hasegawa
1   Division of Molecular Medicine, Graduate School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan
2   Clinical Research Institute, National Hospital Organization Kyoto Medical Center, Kyoto, Japan
,
Tatsuya Morimoto 
1   Division of Molecular Medicine, Graduate School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan
2   Clinical Research Institute, National Hospital Organization Kyoto Medical Center, Kyoto, Japan
3   Shizuoka General Hospital, Shizuoka, Japan
› Author AffiliationsSupported by: Meiji Co., Ltd. A185-05
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Abstract

Pathological stresses such as pressure overload and myocardial infarction induce cardiac hypertrophy, which increases the risk of heart failure. Cacao bean polyphenols have recently gained considerable attention for their beneficial effects on cardiovascular diseases. This study investigated the effect of cacao bean polyphenols on the development of cardiac hypertrophy and heart failure. Cardiomyocytes from neonatal rats were pre-treated with cacao bean polyphenols and then stimulated with 30 µM phenylephrine. C57BL/6j male mice were subjected to sham or transverse aortic constriction surgery and then orally administered with vehicle or cacao bean polyphenols. Cardiac hypertrophy and function were examined by echocardiography. In cardiomyocytes, cacao bean polyphenols significantly suppressed phenylephrine-induced cardiomyocyte hypertrophy and hypertrophic gene transcription. Extracellular signal-regulated kinase 1/2 and GATA binding protein 4 phosphorylation induced by phenylephrine was inhibited by cacao bean polyphenols treatment in the cardiomyocytes. Cacao bean polyphenols treatment at 1200 mg/kg significantly ameliorated left ventricular posterior wall thickness, fractional shortening, hypertrophic gene transcription, cardiac hypertrophy, cardiac fibrosis, and extracellular signal-regulated kinase 1/2 phosphorylation induced by pressure overload. In conclusion, these findings suggest that cacao bean polyphenols prevent pressure overload-induced cardiac hypertrophy and systolic dysfunction by inhibiting the extracellular signal-regulated kinase 1/2-GATA binding protein 4 pathway in cardiomyocytes. Thus, cacao bean polyphenols may be useful for heart failure therapy in humans.

Key words

cacao bean polyphenols - cardiac hypertrophy - heart failure - ERK1/2

Supporting Information

    Original western blot images are shown in Supplementary Figs. 1 – 3S. Body and organ weight of mice treated with CBPs are shown in Supplementary Fig. 4S. The primer sequences used in this study are shown in Supplementary Table 1S.

  • Supporting Information


Publication History

Received: 06 January 2020

Accepted after revision: 31 May 2020

Article published online:
09 July 2020

© 2020. Thieme. All rights reserved.

Georg Thieme Verlag KG
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