Astragalus membranaceus injection activates mitophagy and protects mitochondrial function in chronic heart failure via inhibiting AKT/mTOR pathway
Nov 29, 2025Scientific reports
Astragalus membranaceus injection may protect heart cells in chronic heart failure by activating mitochondrial cleanup through AKT/mTOR pathway inhibition
AMI treatment significantly improved left ventricular ejection fraction in TAC-induced chronic heart failure mice.
AMI dose-dependently suppressed pathological hypertrophy and attenuated apoptosis in hypertrophic cardiomyocytes.
Treatment with AMI restored mitochondrial function and enhanced mitophagic flux in vitro.
In vivo, AMI increased the number of mitochondria and elevated autophagy in TAC mice.
The PI3K/ was identified as the primary regulatory mechanism for AMI's cardioprotective effects.
Pharmacological activation of AKT/mTOR signaling suppressed mitophagic flux, while AMI treatment restored and mitochondrial homeostasis.
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To investigate the effects and mechanisms of Astragalus Membranaceus Injection (AMI) on and mitochondrial function in chronic heart failure (CHF) based on phosphoproteomic and network pharmacology analysis. Primary neonatal mouse cardiomyocytes were isolated and hypertrophy cardiomyocyte model was induced by phenylephrine (PE) stimulation. AMI's effects on cell size, apoptosis, mitophagy, and mitochondrial function in hypertrophic cardiomyocytes were assessed. A pressure-overload CHF model was established via transverse aortic constriction (TAC) surgery in C57BL/6N mice. Echocardiography and histopathology were employed to evaluate AMI's effects on cardiac function and structural remodeling. Transmission electron microscope (TEM) and immunofluorescence were used to detect the distribution of autophagosomes and mitochondria. Phosphorylation-antibody microarray and network pharmacology were employed to explore AMI's cardioprotective mechanisms. The 's involvement was verified through Western blotting of AKTand mTORphosphorylation and pharmacological validation using SC79 (AKT/mTOR activator) and GSK-690693 (AKT/mTOR inhibitor) in gain/loss-of-function experiments. In vitro, AMI dose-dependently suppressed pathological hypertrophy, attenuated apoptosis, restored mitochondrial function, and enhanced mitophagic flux. In vivo, AMI treatment significantly improved left ventricular ejection fraction while attenuated cardiac hypertrophy and interstitial fibrosis in TAC-induced CHF mice. Besides, AMI treatment increased the number of mitochondria and elevated autophagy in TAC mice. Phosphoproteomic screening and network pharmacology analysis identified the PI3K/AKT/mTOR axis as the primary regulatory pathway mediating AMI's cardioprotection. Pharmacological activation of AKT/mTOR signaling using SC79 significantly suppressed mitophagic flux, whereas AMI treatment mirrored the effects of the AKT/mTOR inhibitor GSK-690693, effectively restoring mitophagy and mitochondrial homeostasis. AMI exerts its cardioprotective effects through inhibition of the AKT/mTOR pathway, thereby ameliorating maladaptive remodeling and mitochondrial dysfunction in CHF. Ser473Ser2481
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