A Food-Derived Flavonoid Luteolin Protects against Angiotensin II-Induced Cardiac Remodeling.
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.
Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Atsuko
A
Nakayama
Department of Translational Research for Healthcare and Clinical Science, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Hiroyuki
H
Morita
Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Tomoko
T
Nakao
Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Toshihiro
T
Yamaguchi
Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Tomokazu
T
Sumida
Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Yuichi
Y
Ikeda
Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Hidetoshi
H
Kumagai
Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Yoshihiro
Y
Motozawa
Theravalues Corporation, Tokyo, Japan.
Tsukasa
T
Takahashi
Theravalues Corporation, Tokyo, Japan.
Atsushi
A
Imaizumi
Theravalues Corporation, Tokyo, Japan.
Tadashi
T
Hashimoto
Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Ryozo
R
Nagai
Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Issei
I
Komuro
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D009320:Atrial Natriuretic Factor / Q000378:metabolism; D055513:Connective Tissue Growth Factor / Q000378:metabolism; D004032:Diet; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005355:Fibrosis / Q000188:drug therapy / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology*; D005502:Food; D006321:Heart / Q000187:drug effects*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D006984:Hypertrophy / Q000188:drug therapy / Q000378:metabolism; D047311:Luteolin / Q000494:pharmacology*; D008297:Male; D009206:Myocardium / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D020257:Ventricular Remodeling / Q000187:drug effects*
D000975:Antioxidants; C526316:CCN2 protein, rat; D005419:Flavonoids; D053773:Transforming Growth Factor beta1; D000804:Angiotensin II; D055513:Connective Tissue Growth Factor; D009320:Atrial Natriuretic Factor; D006861:Hydrogen Peroxide; D047311:Luteolin