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

Abstract

Context: Heart failure (HF) is one of the most serious diseases worldwide. Astragaloside IV (ASI) is widely used for the treatment of cardiovascular disease in China. Objective: To evaluate the protective effect of ASI on the HF in a Sprague-Dawley rat model of left coronary artery ligation, and investigate the angiogenesis-related mechanisms. Materials and methods: Left coronary artery was ligated to induce a rat model of HF, and the rats were treated with vehicle (saline) or different doses of ASI (0.1, 0.3 and 1 mg/kg/day) by oral gavage for 6 weeks. Cardiac function was evaluated by echocardiography. Infarct size was determined by triphenyltetrazolium chloride staining. Cardiac vascular density was analyzed by microangiography. Real-time PCR, Western blot and chromatin immunoprecipitation were performed to investigate the mechanisms. Results: ASI treatment improved the body weight and survival rate of HF rats, as well as the cardiac function of HF rats, with significantly improved ejection fraction (75.27 ± 5.75% vs. 36.26 ± 4.14%) and fractional shortening (45.39 ± 3.66% vs. 17.88 ± 1.32%). ASI reduced the infarct size of the HF rats by 47%. ASI promoted angiogenesis, with increased vascular density (2.08fold) and induced mRNA expression of CD31 (1.81-fold) and VEGF (2.70-fold) in the ischemic heart. Furthermore, ASI induced the phosphorylation of JAK (1.89-fold) and STAT3 (2.95-fold), as well as the activity of VEGF promoter which was regulated by STAT3. Discussion and conclusions: ASI alleviated HF by promoting angiogenesis through JAK-STAT3 pathway, providing novel alternative strategies to prevent HF in the future.

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.…”

aFGF Targeted Mediated by Novel Nanoparticles-Microbubble Complex Combined With Ultrasound-Targeted Microbubble Destruction attenuates Doxorubicin-Induced Heart Failure via Anti-Apoptosis and Promoting Cardiac Angiogenesis

“…Recent studies have shown that AngⅡ-induced angiogenesis damage was closely related to p53dependent downregulation of HIF-1 mediated by Jagged1/Notch1 signal pathway (Guan et al, 2017). The decrease of capillary density in hypertrophic myocardium and the increase of diffusion distance from capillaries to the center of cardiomyocytes lead to myocardial ischemia and hypoxia, which is an important mechanism leading to heart failure (Ruan et al, 2018;Sui et al, 2019).…”

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

“…ASI has been shown to improve cardiac function and inhibit compensatory hypertrophy and ventricle remodelling in rats with congestive heart failure (Wang et al 2010;Tang et al 2018). Our previous study reported that ASI alleviated heart failure by promoting angiogenesis through a JAK-STAT3 pathway (Sui et al 2019). However, it is not clear whether the effect of ASI on heart failure is related to the mechanism of antioxidation.…”