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

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.

Targeting the epigenome: Screening bioactive compounds that regulate histone deacetylase activity

“…epigallocatechin gallate (EGCG), luteolin, kaempferol) as cardioprotective . Luteolin for instance protects against ischemia/reperfusion‐induced myocardial injury as well as angiotensin II‐induced cardiac remodeling . In addition to this, some of our compounds have previously been implicated in the regulation of PTMs that include phosphorylation, acetylation, and methylation in other chronic disease states .…”

“…Indeed, reports have highlighted a role for some of our identified compounds (e.g. epigallocatechin gallate (EGCG), luteolin, kaempferol) as cardioprotective . Luteolin for instance protects against ischemia/reperfusion‐induced myocardial injury as well as angiotensin II‐induced cardiac remodeling .…”

Luteolin attenuates sepsis‑induced myocardial�injury by enhancing autophagy in mice

“…Increasing evidence has demonstrated that luteolin has a certain therapeutic effect on cardiovascular disease, including preventing ischemia/reperfusion injury in adult rats (14) and sodium fluoride-induced hypertension in rats (28), ameliorating inorganic mercury-induced cardiac injury in rats (29), decreasing high-carbohydrate/high-fat diet-induced myocardial inflammation (15), and improving angiotensin II-induced cardiac remodeling by decreasing oxidative stress (16). SIc, first described by Parker et al (30) in 1984, is a complication of severe sepsis and septic shock characterized by an invertible myocardial depression.…”

“…These cardiovascular protective effects of luteolin may be due to its antioxidant activities. For example, luteolin can improve angiotensin II-induced cardiac remodeling by decreasing oxidative stress (16). While increasing evidence shows that luteolin exerts cardiovascular protective effects, the possible beneficial effects of luteolin on SIC have not yet been fully clarified.…”

Luteolin: A Flavonoid that Has Multiple Cardio-Protective Effects and Its Molecular Mechanisms

“…It stimulates pro-fibrotic cytokine transforming growth factor β (TGFβ1) expression ( Rosenkranz, 2004 ). Nakayama et al (2015) clearly demonstrated that in Ang II-induced hypertension rats, TGF β1, CTGF, Nox2, and Nox4 gene expression were increased and oral pretreatment with a high-luteolin diet restored the above indices, and also suppressed H 2 O 2 -induced TGFβ1 expression. Food-derived Lut may be a therapeutic strategy through the inhibition of Ang II-induced cardiac remodeling ( Nakayama et al, 2015 ).…”