Isorhamnetin protects against cardiac hypertrophy through blocking PI3K-AKT pathway.
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.
Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, No.1 Jianshe East Road, Zhengzhou, 450052, China.
Lu
L
Gao
Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, No.1 Jianshe East Road, Zhengzhou, 450052, China.
Rui
R
Yao
Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, No.1 Jianshe East Road, Zhengzhou, 450052, China.
Yuzhou
Y
Liu
Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, No.1 Jianshe East Road, Zhengzhou, 450052, China.
Zheng
Z
Wang
Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, No.1 Jianshe East Road, Zhengzhou, 450052, China.
Zhen
Z
Huang
Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, No.1 Jianshe East Road, Zhengzhou, 450052, China.
Binbin
B
Du
Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, No.1 Jianshe East Road, Zhengzhou, 450052, China.
Dianhong
D
Zhang
Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, No.1 Jianshe East Road, Zhengzhou, 450052, China.
Leiming
L
Wu
Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, No.1 Jianshe East Road, Zhengzhou, 450052, China.
Lili
L
Xiao
Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, No.1 Jianshe East Road, Zhengzhou, 450052, China. yzzhang6@163.com.
Yanzhou
Y
Zhang
D000804:Angiotensin II / Q000009:adverse effects; D000818:Animals; D006332:Cardiomegaly / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism; D002316:Cardiotonic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D004452:Echocardiography; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D051379:Mice; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D011794:Quercetin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects
D002316:Cardiotonic Agents; C047368:3-methylquercetin; D000804:Angiotensin II; D011794:Quercetin; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt
AKT; Cardiac hypertrophy; Isorhamnetin; PI3K; Pressure overload