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

Nurmila Sari; Yasufumi Katanasaka; Hiroki Honda; Yusuke Miyazaki; Yoichi Sunagawa; Masafumi Funamoto; Kana Shimizu; Satoshi Shimizu; Hiromichi Wada; Koji Hasegawa; Tatsuya Morimoto

doi:10.1055/a-1191-7970

Planta Medica, Table of Contents

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

¹Division of Molecular Medicine, Graduate School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan

,

Yasufumi Katanasaka

¹Division of Molecular Medicine, Graduate School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan

²Clinical Research Institute, National Hospital Organization Kyoto Medical Center, Kyoto, Japan

³Shizuoka General Hospital, Shizuoka, Japan

,

Hiroki Honda

¹Division of Molecular Medicine, Graduate School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan

,

Yusuke Miyazaki

¹Division of Molecular Medicine, Graduate School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan

²Clinical Research Institute, National Hospital Organization Kyoto Medical Center, Kyoto, Japan

³Shizuoka General Hospital, Shizuoka, Japan

,

Yoichi Sunagawa

¹Division of Molecular Medicine, Graduate School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan

²Clinical Research Institute, National Hospital Organization Kyoto Medical Center, Kyoto, Japan

³Shizuoka General Hospital, Shizuoka, Japan

,

Masafumi Funamoto

¹Division of Molecular Medicine, Graduate School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan

²Clinical Research Institute, National Hospital Organization Kyoto Medical Center, Kyoto, Japan

,

Kana Shimizu

¹Division of Molecular Medicine, Graduate School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan

²Clinical Research Institute, National Hospital Organization Kyoto Medical Center, Kyoto, Japan

,

Satoshi Shimizu

¹Division of Molecular Medicine, Graduate School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan

²Clinical Research Institute, National Hospital Organization Kyoto Medical Center, Kyoto, Japan

,

Hiromichi Wada

²Clinical Research Institute, National Hospital Organization Kyoto Medical Center, Kyoto, Japan

,

Koji Hasegawa

¹Division of Molecular Medicine, Graduate School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan

²Clinical Research Institute, National Hospital Organization Kyoto Medical Center, Kyoto, Japan

,

Tatsuya Morimoto

¹Division of Molecular Medicine, Graduate School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan

²Clinical Research Institute, National Hospital Organization Kyoto Medical Center, Kyoto, Japan

³Shizuoka General Hospital, Shizuoka, Japan

› Author Affiliations

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

Full Text

References

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