Astragaloside IV Attenuates Myocardial Ischemia‐Reperfusion Injury via Suppression of the NOX4/ROS Axis: Mechanistic Insights From In Vivo and In Vitro Models

Myocardial ischemia‐reperfusion injury (MIRI) stands as a critical determinant undermining the therapeutic efficacy of revascularization procedures in treating myocardial infarction cases. Among the various injury mechanisms discussed herein, oxidative stress plays a crucial role, with nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4) identified as a key enzyme responsible for orchestrating the production of reactive oxygen species (ROS). Astragaloside IV (AS‐IV), an extract derived from Astragalus membranaceus , a traditional Chinese medicinal herb, exhibits antioxidative stress properties. In this study, we aimed to investigate the efficacy of AS‐IV in mitigating MIRI and to elucidate the underlying regulatory mechanisms. We established a model of MIRI in Sprague–Dawley (SD) rats and employed an oxygen‐dependent glycan deprivation/reoxygenation (OGD/R) model using the rat myocardial H9C2 cell line. AS‐IV treatment significantly mitigated cardiac functional injury, pathological damage, and the infarct area resulting from ischemia‐reperfusion (I/R). Furthermore, AS‐IV administration effectively reduced oxidative stress levels both in vitro and in vivo. It has been demonstrated that AS‐IV modulates ROS production and alleviates oxidative stress associated with I/R injury by inhibiting NOX4 expression. Therefore, AS‐IV exhibits considerable potential as a therapeutic intervention for the management of myocardial I/R.