6-Shogaol, an Active Component of Ginger, Inhibits p300 Histone Acetyltransferase Activity and Attenuates the Development of Pressure-Overload-Induced Heart Failure

Yuto Kawase; Yoichi Sunagawa; Kana Shimizu; Masafumi Funamoto; Toshihide Hamabe-Horiike; Yasufumi Katanasaka; Satoshi Shimizu; Philip Hawke; Kiyoshi Mori; Maki Komiyama; Koji Hasegawa; Tatsuya Morimoto

doi:10.3390/nu15092232

6-Shogaol, an Active Component of Ginger, Inhibits p300 Histone Acetyltransferase Activity and Attenuates the Development of Pressure-Overload-Induced Heart Failure

Nutrients. 2023 May 8;15(9):2232. doi: 10.3390/nu15092232.

Authors

Yuto Kawase¹, Yoichi Sunagawa^{1

2

3}, Kana Shimizu^{1

2}, Masafumi Funamoto^{1

2

4}, Toshihide Hamabe-Horiike^{1

2

3}, Yasufumi Katanasaka^{1

2

3}, Satoshi Shimizu^{1

2}, Philip Hawke⁵, Kiyoshi Mori^{1

3

6}, Maki Komiyama², Koji Hasegawa^{1

2}, Tatsuya Morimoto^{1

2

3}

Affiliations

¹ Division of Molecular Medicine, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka 422-8526, Japan.
² Division of Translational Research, National Hospital Organization Kyoto Medical Center, Kyoto 612-8555, Japan.
³ Shizuoka General Hospital, Shizuoka 420-8527, Japan.
⁴ Department of Pharmacology, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima 770-8503, Japan.
⁵ Laboratory of Scientific English, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka 422-8526, Japan.
⁶ Graduate School of Public Health, Shizuoka Graduate University of Public Health, Shizuoka 420-0881, Japan.

Abstract

Hypertrophic stress-induced cardiac remodeling is a compensatory mechanism associated with cardiomyocyte hypertrophy and cardiac fibrosis. Continuation of this response eventually leads to heart failure. The histone acetyltransferase p300 plays an important role in the development of heart failure, and may be a target for heart failure therapy. The phenolic phytochemical 6-shogaol, a pungent component of raw ginger, has various bioactive effects; however, its effect on cardiovascular diseases has not been investigated. One micromolar of 6-shogaol suppressed phenylephrine (PE)-induced increases in cardiomyocyte hypertrophy in rat primary cultured cardiomyocytes. In rat primary cultured cardiac fibroblasts, 6-shogaol suppressed transforming growth factor-beta (TGF-β)-induced increases in L-proline incorporation. It also blocked PE- and TGF-β-induced increases in histone H3K9 acetylation in the same cells and in vitro. An in vitro p300-HAT assay revealed that 6-shogaol suppressed histone acetylation. The mice underwent transverse aortic constriction (TAC) surgery, and were administered 0.2 or 1 mg/kg of 6-shogaol daily for 8 weeks. 6-shogaol prevented TAC-induced systolic dysfunction and cardiac hypertrophy in a dose-dependent manner. Furthermore, it also significantly inhibited TAC-induced increases in histone H3K9 acetylation. These results suggest that 6-shogaol may ameliorate heart failure through a variety of mechanisms, including the inhibition of p300-HAT activity.

Keywords: 6-shogaol; cardiac remodeling; heart failure; histone acetyltransferase; p300.

MeSH terms

Acetylation
Animals
Anti-Arrhythmia Agents
Aortic Valve Stenosis*
Cardiotonic Agents
Diuretics
Glycosides
Heart Failure* / drug therapy
Heart Failure* / etiology
Histones
Mice
Rats
Zingiber officinale*

Substances

shogaol
Histones
Anti-Arrhythmia Agents
Cardiotonic Agents
Diuretics
Glycosides

Grants and funding

This work was supported in part by funding from the Japan Science and Technology Agency (20K07070, T.M.; 19K16396, Y.S.; and 21K08069, K.H.), the Cardiovascular Research Fund (Y.S.), a Japan Heart Foundation Research Grant (Y.S.), the Nutrition and Food Science Fund of the Japan Society of Nutrition and Food Science (Y.S.), and the Mochida Memorial Foundation for Medical and Pharmaceutical Research (Y.S.).