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.
| Original language | English (US) |
|---|---|
| Article number | e0137106 |
| Journal | PLoS One |
| Volume | 10 |
| Issue number | 9 |
| DOIs | |
| State | Published - Sep 1 2015 |
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ASJC Scopus subject areas
- Agricultural and Biological Sciences(all)
- Biochemistry, Genetics and Molecular Biology(all)
- Medicine(all)
Cite this
A food-derived flavonoid luteolin protects against angiotensin II-induced cardiac remodeling. / 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.
In: PLoS One, Vol. 10, No. 9, e0137106, 01.09.2015.Research output: Contribution to journal › Article
}
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
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.
UR - http://www.scopus.com/inward/record.url?scp=84943339706&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84943339706&partnerID=8YFLogxK
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 -