Astragaloside IV alleviates heart failure via activating PPARα to switch glycolysis to fatty acid β-oxidation

Abstract

In heart failure (HF), energy metabolism pathway in cardiac muscle changes from fatty acid β-oxidation to glycolysis. However, the exact mechanism is unknown. Sarcoendoplasmic reticulum Ca2+α ATPase (SERCA) expression is downregulated and mitochondrial function is reduced in HF, perhaps partly due to a substantially reduced energy supply for excitation–contraction coupling resulting from a lower fatty acid β-oxidation rate. We investigated whether Astragaloside IV can activate peroxisome proliferator-activated receptor alpha (PPARα) to stimulate fatty acid β-oxidation and increase cardiac energy production, improving mitochondrial function and the efficiency of SERCA in HF. In pressure overload-induced HF mice and isolated hypertrophic myocardial cells, fatty acid β-oxidation and heart function were substantially strengthened following Astragaloside IV treatment, as demonstrated by the increased expression of PPARα and SERCA2a. In vitro, Astragaloside IV regulated energy metabolism by increasing ATP production and enhancing mitochondrial function, attributable to increased oxygen consumption and slightly increased mitochondrial Ca2+ uptake. In HF, Astragaloside IV switched glycolysis to fatty acid β-oxidation, as confirmed by reduced anaerobic glycolysis and an increased oxygen consumption ratio. These results suggest that Astragaloside IV can stimulate fatty acid β-oxidation and improve mitochondrial function, which may present a novel cardioprotective treatment that inhibits the progress of HF.

Astragaloside IV alleviates heart failure by promoting angiogenesis through the JAK-STAT3 pathway

“…A large number of clinical trials which were carried out in Chinese hospitals reported that Astragalus membranaceus could improve the left ventricular function and mitigate the cardiac hypertrophy in HF patients (Yuang 2003). Recently, increasing evidence showed that ASI, a saponin, is the active ingredient of A. membranaceus in the treatment of HF (Zhao et al 2009;Wang et al 2010;Dong et al 2017). Previous studies reported that ASI improved EF, FS, and LV dimensions in rat and mouse model of HF which was induced by left coronary artery ligation (Zhao et al 2009;Wang et al 2010;Dong et al 2017).…”

“…Recently, increasing evidence showed that ASI, a saponin, is the active ingredient of A. membranaceus in the treatment of HF (Zhao et al 2009;Wang et al 2010;Dong et al 2017). Previous studies reported that ASI improved EF, FS, and LV dimensions in rat and mouse model of HF which was induced by left coronary artery ligation (Zhao et al 2009;Wang et al 2010;Dong et al 2017). In our study, ASI improved the body weight and survival rate of HF rats, as well as the cardiac function of HF rats, which was consistent with the previous data.…”

“…Astragaloside IV (ASI) is the major active constituent of Astragalus propinquus Schischkin (Fabaceae), a widely used herb for the treatment of cardiovascular disease in China (Miller 1998;Sinclair 1998). Previous studies reported effects of ASI on HF in rats (Zhao et al 2009;Wang et al 2010;Dong et al 2017). In addition, ASI stimulated angiogenesis in human umbilical vein endothelial cells, including cell proliferation, migration, and tube formation (Zhang et al 2011;Wang et al 2013).…”

Astragaloside IV reverses MNNG‐induced precancerous lesions of gastric carcinoma in rats: Regulation on glycolysis through miRNA‐34a/LDHA pathway

“…Moreover, studies have demonstrated that ASIV, a marker for the active constituent in A . membranaceus , was further proven to be responsive component for glycolysis regulation (Dong et al, ). Therefore, the role of the glycolysis‐regulating effect of ASIV in curing PLGC is needed to be further elucidate.…”

Exploration the mechanism of doxorubicin-induced Heart failure in Rats by integration of proteomics and metabolomics data

“…Removing mitochondrial oxidative phosphorylation, the main source of ATP is fatty acid oxidation, followed by glucose oxidation, amino acid oxidation and so on. In heart failure, energy production is converted from fatty acid beta-oxidation to glucose oxidation, which contributes to the progressive deterioration of cardiac function in hypertrophy and heart failure (Dong et al, 2017).In this study, carnitine and Acaa2, Acads showed a downward trend, which proved that the oxidation ability of fatty acids was affected and cardiac function was impaired (Bertero and Maack, 2018). Studies in knockdown PTP1B mice have shown that PTP1B protein has signi cant effects on insulin sensitivity, glucose homeostasis and lipid metabolism (Owen et al, 2013;Zhang et al, 2016).…”