A Food-Derived Flavonoid Luteolin Protects against Angiotensin II-Induced Cardiac Remodeling |
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| Authors: | 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 |
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| Institution: | 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.; Universidade Federal do Rio de Janeiro, BRAZIL, |
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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. |
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