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

• Published in: PloS one 2015-09, Vol.10 (9), p.e0137106-e0137106
• Main Authors: Nakayama, Atsuko, Morita, Hiroyuki, Nakao, Tomoko, Yamaguchi, Toshihiro, Sumida, Tomokazu, Ikeda, Yuichi, Kumagai, Hidetoshi, Motozawa, Yoshihiro, Takahashi, Tsukasa, Imaizumi, Atsushi, Hashimoto, Tadashi, Nagai, Ryozo, Komuro, Issei
• Format: Article
• Language: English
• Subjects: Angiotensin; Angiotensin II; Angiotensin II - pharmacology; Animals; Antioxidants; Antioxidants - pharmacology; Atrial Natriuretic Factor - metabolism; Cardiomyopathy; Care and treatment; Celery; Connective tissue growth factor; Connective Tissue Growth Factor - metabolism; CYBB protein; Development and progression; Diet; Drug dosages; Experiments; Fibroblasts; Fibroblasts - drug effects; Fibroblasts - metabolism; Fibrosis; Fibrosis - drug therapy; Fibrosis - metabolism; Flavonoids; Flavonoids - pharmacology; Food; Gene expression; Health aspects; Heart; Heart - drug effects; Heart diseases; Heart failure; Heart hypertrophy; Herbal medicine; Hydrogen peroxide; Hydrogen Peroxide - pharmacology; Hypertension; Hypertrophy; Hypertrophy - drug therapy; Hypertrophy - metabolism; JNK protein; Liver; Lungs; Luteolin - pharmacology; Male; Medicine; Metabolism; Myocardium - metabolism; NOX4 protein; Nutrition; Oxidative stress; Oxidative Stress - drug effects; Patient outcomes; Phosphorylation; Phosphorylation - drug effects; Plant extracts; Pretreatment; Rats; Rats, Sprague-Dawley; Risk factors; Rodents; Seeds; Signal Transduction - drug effects; Transforming Growth Factor beta1 - metabolism; Transforming growth factor-b1; Ventricular Remodeling - drug effects
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0137106

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.