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Oxid Med Cell Longev. 2019 Jun 11;2019:4625912. doi: 10.1155/2019/4625912. eCollection 2019.

Astragaloside IV Exerts a Myocardial Protective Effect against Cardiac Hypertrophy in Rats, Partially via Activating the Nrf2/HO-1 Signaling Pathway.

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1
Jining Medical University, Jining 272067, China.
2
Department of Cardiology, Affiliated Hospital of Jining Medical University, Jining 272029, China.

Abstract

Previous evidence suggested that astragaloside IV (ASIV) had a cardioprotective effect, but the potential mechanisms were undetermined. This study is aimed at validating the prevention of cardiac hypertrophy in chronic heart failure (CHF) rats and hypertrophy in H9c2 cardiomyocytes by ASIV and at exploring the potential mechanism involved. CHF rat models of abdominal aortic constriction (AAC) were used with the aim of determining the protective effect of ASIV in cardiac hypertrophy in the rats. We proved that ASIV could attenuate cardiac hypertrophy by improving left ventricular function and structure and showed that the expression of nuclear factor-erythroid 2-related factor 2 (Nrf2) and its downstream gene heme oxygenase-1 (HO-1) increased in the high-dose ASIV intervention group. To further investigate the specific mechanism of ASIV, we hypothesized that ASIV might prevent cardiac hypertrophy via activating the Nrf2/HO-1 signaling pathway. We established a cardiomyocyte hypertrophy model induced by angiotensin II (Ang II), which was then transfected with Nrf2 shRNA, to knock down the expression of the Nrf2 gene. We found that the protective effect of ASIV against Ang II-induced cardiomyocyte hypertrophy was abolished in the Nrf2 shRNA transfection group, ultimately aggravating cardiomyocyte hypertrophy induced by Ang II, and it is possible that oxidative stress may be involved in this process. Our results demonstrated that ASIV improved cardiac function and inhibited cardiac hypertrophy by upregulating Nrf2, and this effect was partially achieved by stimulating the Nrf2/HO-1 signaling pathway, suggesting that ASIV could have therapeutic potential for the treatment of cardiac hypertrophy and CHF.

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