Fraxin alleviates myocardial infarction dysfunction by decreasing oxidative stress via PI3K/AKT-mediated upregulation...

Acute myocardial infarction (AMI) is a persistent ischaemic and anoxic necrosis of the myocardium that triggers oxidative stress and ultimately leads to remodelling and heart failure. Fraxin is a traditional Chinese medicine that is commonly used in clinical practice. In this study, Fraxin improved cardiac function, reduced the area of myocardial infarction, and reduced cardiac damage such as myocardial inflammation and fibrosis. Fraxin reduced myocardial oxidative stress injury, myocardial inflammation index and myocardial apoptosis level. Network pharmacology analysis identified hexokinase II (HXK2) as the key target protein and the phosphatidylinositol-3-kinase (PI3K)/AKT pathway as the key signalling pathway. Molecular docking revealed strong binding affinity between Fraxin and HXK2. Fraxin was found to reduce oxidative stress damage, inflammation and apoptosis by enhancing HXK2's mitochondrial localization and its interaction with voltage-dependent anion channels (VDAC) via HXK2 inhibitors and HXK2-VDAC binding domain peptides. Furthermore, inhibition of the PI3K/AKT signalling pathway abolished the regulatory effects of Fraxin on HXK2 during myocardial infarction. Taken together, Fraxin exerts a cardioprotective effect by regulating HXK2 through PI3K/AKT signaling pathway to reduce reactive oxygen species (ROS) levels, inflammation and myocardial apoptosis. This study provides a scientific basis for the therapeutic potential of the traditional Chinese medicine Fraxin in AMI.