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

Index: PLoS ONE 10 , e0137106, (2015)

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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.