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

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.

The role of Nrf2 in astragaloside IV-mediated antioxidative protection on heart failure

“…Such a result was consistent with recently published data showing that ASI induced Nrf2/HO-1 protein expressions in the myocardium in a rat model of abdominal aortic constriction (Nie et al. 2019 ).…”

“…In this study, we reported increased protein expression of Nrf2 and its downstream signal molecule HO-1 in the myocardial tissue of HF rats. Such a result was consistent with recently published data showing that ASI induced Nrf2/HO-1 protein expressions in the myocardium in a rat model of abdominal aortic constriction (Nie et al 2019).…”

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

“…In addition, research confirms that cycloastragenol improves cardiac defect and remodeling by enhancing autophagy in myocardial cells and reduces the production of MMP-2 and MMP-9 [24]. Previous studies suggest that astragaloside IV corrects cardiac dysfunction and reduces myocardial hypertrophy by activating Nrf2/ HO-1 pathway and PI3K/mTOR pathway and can promote angiogenesis [37][38][39]. is study recruited both identified compounds from TCMSP and the compounds with outstanding pharmacological effects.…”

Chemical Discrimination of Astragalus mongholicus and Astragalus membranaceus Based on Metabolomics Using UHPLC-ESI-Q-TOF-MS/MS Approach

“…Among the chemical components, 68% of them were higher in MJ than in MG. Besides, four primary saponins constituents including Astragaloside I, Astragaloside II, Astragaloside III, and especially Astragaloside IV with anti-cancer [28], anti-oxidant [29], anti-inflammatory [30], immune regulation [31], and metabolic regulation activities [32], among others [33,34,35], in MJ were distinctly higher than that in MG. The result offered evidence that MJ may own stronger pharmacological activity and wider application than MG.…”