A Food-Derived Flavonoid Luteolin Protects against Angiotensin II-Induced Cardiac Remodeling

Atsuko Nakayama; Hiroyuki Morita; Tomoko Nakao; Toshihiro Yamaguchi; Tomokazu Sumida; Yuichi Ikeda; Hidetoshi Kumagai; Yoshihiro Motozawa; Tsukasa Takahashi; Atsushi Imaizumi; Tadashi Hashimoto; Ryozo Nagai; Issei Komuro

doi:10.1371/journal.pone.0137106

A Food-Derived Flavonoid Luteolin Protects against Angiotensin II-Induced Cardiac Remodeling

PLoS One. 2015 Sep 1;10(9):e0137106. doi: 10.1371/journal.pone.0137106. eCollection 2015.

Affiliations

¹ Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
² Department of Translational Research for Healthcare and Clinical Science, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
³ Theravalues Corporation, Tokyo, Japan.

Abstract

Oxidative stress has been implicated in cardiac remodeling (cardiac fibrosis and hypertrophy), which impairs cardiac function and metabolism; therefore, it is anticipated antioxidative compounds will have protective properties against cardiac remodeling. Luteolin (3',4',5,7-tetrahydroxyflavone), a widely distributed flavonoid found in many herbal extracts including celery, green pepper, perilla leaves and seeds, and chamomile, is a known to be a potent antioxidant and was previously demonstrated to exert an antifibrotic effect in the lungs and the liver. In this study, we clearly demonstrate that oral pretreatment with the higher-luteolin diet (0.035% (wt/wt)) protected against cardiac fibrosis and hypertrophy as well as a hyperoxidative state in Ang II-infused rats. In cardiac tissue, increased gene expression levels of TGFβ1, CTGF, Nox2, Nox4, ANP, and BNP induced by Ang II were restored by oral pretreatment of this high-luteolin diet. In cultured rat cardiac fibroblasts, H2O2-induced TGFβ1 expression and the phosphorylation of JNK were suppressed by luteolin pretreatment. In conclusion, food-derived luteolin has protective actions against Ang II-induced cardiac remodeling, which could be mediated through attenuation of oxidative stress.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Angiotensin II / pharmacology*
Animals
Antioxidants / pharmacology
Atrial Natriuretic Factor / metabolism
Connective Tissue Growth Factor / metabolism
Diet
Fibroblasts / drug effects
Fibroblasts / metabolism
Fibrosis / drug therapy
Fibrosis / metabolism
Flavonoids / pharmacology*
Food
Heart / drug effects*
Hydrogen Peroxide / pharmacology
Hypertrophy / drug therapy
Hypertrophy / metabolism
Luteolin / pharmacology*
Male
Myocardium / metabolism
Oxidative Stress / drug effects
Phosphorylation / drug effects
Rats
Rats, Sprague-Dawley
Signal Transduction / drug effects
Transforming Growth Factor beta1 / metabolism
Ventricular Remodeling / drug effects*

Substances

Antioxidants
CCN2 protein, rat
Flavonoids
Transforming Growth Factor beta1
Angiotensin II
Connective Tissue Growth Factor
Atrial Natriuretic Factor
Hydrogen Peroxide
Luteolin

Grants and funding

This research is supported by the Theravalues Corporation (Tokyo, Japan). The funder provided support in the form of salaries for authors TT, AI, TH, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.