Isorhamnetin protects against cardiac hypertrophy through blocking PI3K–AKT pathway

Abstract

Isorhamnetin, a flavonoid compound extracted from the Chinese herb Hippophae rhamnoides L., is well known for its anti-inflammatory, anti-oxidative, anti-adipogenic, anti-proliferative, and anti-tumor activities. However, the role of isorhamnetin in cardiac hypertrophy has not been reported. The aims of the present study were to find whether isorhamnetin could alleviate cardiac hypertrophy and to define the underlying molecular mechanisms. Here, we investigated the effects of isorhamnetin (100 mg/kg/day) on cardiac hypertrophy induced by aortic banding in mice. Cardiac hypertrophy was evaluated by echocardiographic, hemodynamic, pathological, and molecular analyses. Our data demonstrated that isorhamnetin could inhibit cardiac hypertrophy and fibrosis 8 weeks after aortic banding. The results further revealed that the effect of isorhamnetin on cardiac hypertrophy was mediated by blocking the activation of phosphatidylinositol 3-kinase-AKT signaling pathway. In vitro studies performed in neonatal rat cardiomyocytes confirmed that isorhamnetin could attenuate cardiomyocyte hypertrophy induced by angiotensin II, which was associated with phosphatidylinositol 3-kinase-AKT signaling pathway. In conclusion, these data indicate for the first time that isorhamnetin has protective potential for targeting cardiac hypertrophy by blocking the phosphatidylinositol 3-kinase-AKT signaling pathway. Thus, our study suggests that isorhamnetin may represent a potential therapeutic strategy for the treatment of cardiac hypertrophy and heart failure.

Exploring Molecular Mechanism of Huangqi in Treating Heart Failure Using Network Pharmacology

“…In the compound-target network, some key 0 -23 33 33 33 33 33 33 33 33 33 33 33 33 33 33 33 - [26]. Moreover, quercetin and isorhamnetin can inhibit the PI3K/AKT signaling pathway activation to protect heart from cardiac hypertrophy and HF [27,28]. Study shows that calycosin and formononetin inhibit the activation of the renin-angiotensin-aldosterone system to improve the symptoms of HF [29].…”

Therapeutic Potential of Polyphenols in Cardiac Fibrosis

“…Taxifolin, one of quercetin derivatives, has the ability to blunt cardiac fibrosis induced by pressure overload, the mechanism underlying anti-fibrotic effect of taxifolin dependents on inhibition of TGF-β/Smad signaling pathway (Guo et al, 2015 ). Isorhamnetin, another ingredient of flavonols, ameliorates cardiac hypertrophy and fibrosis induced by aortic banding (Gao et al, 2017 ). Consistent with the results above, Boerhavia diffusa extracted with ethanol (BDE) is a rich source of bioactive flavonols containing quercetin, boeravinone, kaempferol, and caffeic acid, mitigating Ang II-induced cardiac fibrosis via the inhibition of TGF-β1 expression and collagen deposition (Prathapan et al, 2017 ).…”

Isorhamnetin protects against bleomycin-induced pulmonary fibrosis by inhibiting endoplasmic reticulum stress and epithelial-mesenchymal transition

“…Isorhamnetin (Isor; molecular formula, C 16 H 12 O 7 ), a flavonol aglycone isolated from the plant Hippophae rhamnoides L, is frequently used in traditional Chinese medicine to prevent and treat various diseases. Isor has been demonstrated to exert a variety of effects, including antioxidant, anti-inflammatory, antitumor, antiviral, anti-ERS and neurodegenerative injury protection effects ( 20 , 21 ). Recent research has revealed that Isor attenuates liver fibrosis by inhibiting transforming growth factor (TGF)β/SMAD signaling and relieving oxidative stress ( 22 ).…”