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

Abstract

Context: Heart failure is one of the most serious diseases worldwide. Astragaloside IV (ASI) is widely used in the treatment of cardiovascular diseases. Objective: To elucidate the antioxidative mechanism of ASI in a rat model of left coronary artery ligation. Materials and methods: Left coronary artery of Sprague-Dawley rats was ligated to establish the model of heart failure, and then vehicle (saline) or ASI (1 mg/kg/day) was orally administered to the rats (n ¼ 15) for 6 weeks. Echocardiography was used to evaluate the cardiac function. Myocardial infarct size was measured by triphenyltetrazolium chloride staining. Oxidative stress in the ventricular myocardium was determined. Molecular mechanisms were investigated by Western blot and chromatin immunoprecipitation. Results: ASI improved the cardiac function, especially ejection fraction (75.27 ± 5.75% vs. 36.26 ± 4.14%) and fractional shortening (45.39 ± 3.66% vs. 17.88 ± 1.32%), and reduced the infarct size of left ventricle (20.69 ± 2.98% vs. 39.11 ± 3.97%). ASI maintained the levels of glutathione, catalase and superoxide dismutase and prevented the leakage of creatine kinase. In addition, ASI induced the protein expression of Nrf2 (1.97-fold) and HO-1 (2.79-fold), while reduced that of Keap-1 (0.77-fold) in the ventricular myocardium. In H9c2 cells, a rat cardiomyocyte cell line, ASI induced the translocation of Nrf2 from cytoplasm to nucleus, followed by transcriptional activation of NQO-1 (8.27-fold), SOD-2 (3.27-fold) and Txn-1 (9.83-fold) genes. Discussion and conclusions: ASI prevented heart failure by counteracting oxidative stress through the Nrf2/HO-1 pathway. Application in clinical practice warrants further investigation.

Combination of puerarin and tanshinone IIA alleviates ischaemic stroke injury in rats via activating the Nrf2/ARE signalling pathway

“…Nrf2 binds to the ARE sequences and initiates downstream antioxidation and detoxification enzymes, such as HO-1, NQO1, SOD, CAT, and GSH (Sui et al. 2020 ). In the current study, the key protein expressions of the Nrf2/ARE signalling pathway were increased in the MCAO model, indicating that this pathway was activated against brain tissue damage caused by cerebral ischaemia.…”

The recent advance and prospect of natural source compounds for the treatment of heart failure

“… Mitochondrial function; Myocardial fibrosis. [ [133] , [134] , [135] , [136] ] Momordicoside G Momordica charantia ANP, β-MHC and α-SKA; iNOS and COX-2. Myocardial hypertrophy; Energy metabolism.…”

“…Astragaloside is the main monomer active substance in Astragalus membranaceus , which is also the main index to evaluate the quality of astragalus and the material basis to exert drug effect [ 132 ]. Astragaloside has significant antioxidant activity and protective effect on cardiomyocytes injured by oxidative stress, which is mainly achieved by increasing the reserve respiratory capacity and mitochondrial ATP production [ 133 ]. After 4 weeks of continuous administration of astragaloside, the ratio of early and late filling peak velocity (E/A) and declining rate of left ventricular pressure (-dp/dt) in rats are significantly increased, the expression of protein kinase Cα (PKCα) and calcium ion sensitive receptor are increased, and the activity of SERCA2α is restored, suggesting that astragaloside can promote the recovery of cardiac diastolic function through restoring calcium homeostasis [ 134 ].…”

Activation of Nrf2 signaling: A key molecular mechanism of protection against cardiovascular diseases by natural products

“…Nootkatone is a naturally occurring bioactive sesquiterpene shown to attenuate myocardial OS in ISO-induced MI in by activating the PI3K/Nrf2/Akt cascade ( Meeran et al, 2021 ). Moreover, astragaloside IV has been shown to exert potent cardioprotective effects in various animal models, including abdominal aortic constriction (AB)-induced HF, LAD-induced HF and MIRI, through activation of Nrf2/HO-1 signaling (M. Jiang et al, 2019 ; Nie et al, 2019 ; Sui et al, 2020 ). Astragaloside IV additionally prevents ox-LDL-induced HUVEC injury through mediation of Nrf2/HO-1 signaling (Z.…”