TY - JOUR
T1 - A food-derived flavonoid luteolin protects against angiotensin II-induced cardiac remodeling
AU - Nakayama, Atsuko
AU - Morita, Hiroyuki
AU - Nakao, Tomoko
AU - Yamaguchi, Toshihiro
AU - Sumida, Tomokazu
AU - Ikeda, Yuichi
AU - Kumagai, Hidetoshi
AU - Motozawa, Yoshihiro
AU - Takahashi, Tsukasa
AU - Imaizumi, Atsushi
AU - Hashimoto, Tadashi
AU - Nagai, Ryozo
AU - Komuro, Issei
N1 - Funding Information:
The corresponding author has read the journal's policy and the authors of this manuscript have the following competing interests: This research is supported by Theravalues Corporation (Tokyo, Japan). Tsukasa Takahashi, Atsushi Imaizumi and Tadashi Hashimoto are employed by Theravalues Corporation. In the future, they might participate in the exploitation of a kind of luteolin compound. A. Nakayama, H. Morita, T. Hashimoto, and R. Nagai are named on a patent (Heart failure suppressing agent US 20140194372 A1) for the usefulness of a luteolin compound. There are no further patents, products in development or marketed products to declare. This does not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors.
Publisher Copyright:
© 2015 Nakayama et al.
PY - 2015/9/1
Y1 - 2015/9/1
N2 - 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.
AB - 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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U2 - 10.1371/journal.pone.0137106
DO - 10.1371/journal.pone.0137106
M3 - Article
C2 - 26327560
AN - SCOPUS:84943339706
VL - 10
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 9
M1 - e0137106
ER -