AS-IV alleviates blocking of M3AchR induced myocardial apoptosis through p53/Akt signaling pathway under myocardial ischemia model

Astragaloside IV (AS-IV), as the main active ingredient and nutritional adjunct of Astragali Radix, has a clear cardioprotective effect. However, it is unclear whether AS-IV could protect myocardium from ischemia by activating M3 subtype of muscarinic acetylcholine receptor (M3AchR) receptors and regulate cardiomyocytes apoptosis through p53/Akt. This study aims to establish an in vivo model of myocardial ischemia (MI) and utilize morphological, bioinformatics, and molecular biology methods to elucidate the mechanism by which AS-IV regulates MI and apoptosis through the M3AchR and p53/Akt pathway. The results suggested that AS-IV was able to alleviate the MI injury and aggravated apoptosis of cardiomyocytes caused by M3AchR inhibitors 4-DAMP in vivo. Moreover, AS-IV may have a protective effect on MI by directly acting on M3AchR. Mechanistically, AS-IV's anti-apoptotic effect could be associated with the regulation of the p53/Akt signaling pathway. Collectively, our research indicates that AS-IV could alleviate MI and exert myocardial protective effects by acting on the M3AchR and p53/Akt signaling pathways. This study provides a theoretical basis for exploring potential protective targets of AS-IV and elucidating new functions and mechanisms of AS-IV.