Mangiferin Attenuates Myocardial Ischemia Reperfusion Injury by Regulating the GAS6/Axl Signaling Pathway

ABSTRACT Ischemia reperfusion‐induced myocardial injury is a prominent pathological feature in patients with coronary artery disease, contributing to significant mortality and morbidity rates. Mangiferin (MGF), the main active ingredient extracted from Anemarrhena asphodeloides Bge , has anti‐inflammatory, anti‐oxidation, anti‐diabetes, and anti‐tumor effects. The present study confirmed that the GAS6/Axl pathway was identified as a promising novel target for the treatment of myocardial ischemia reperfusion (IR) injury. However, whether MGF exerts anti‐myocardial ischemia reperfusion injury through GAS6/Axl is still unclear. In this study, BALB/c male mice and HL‐1 cardiomyocytes were used to construct a model of IR and hypoxia‐reoxygenation (HR) (or H 2 O 2 ) injury in vivo and in vitro, respectively. MGF significantly improved cardiac function indicators, myocardial structure, myocardial enzymes, and mitochondrial function, together with reduced oxidative stress and apoptosis in IR‐injured mice. In vitro, MGF significantly increased cell viability, inhibited the release of LDH, reduced oxidative stress and apoptosis, and improved mitochondrial function in both HR and H 2 O 2 ‐injured HL‐1 cells. In particular, the GAS6/Axl signaling pathway plays an important role in this process. Additionally, we also demonstrated that GAS6 gene knockout reversed the protective effect of MGF against HR and H 2 O 2 ‐injured cardiomyocytes. The present study confirmed that MGF has protective effects against myocardial IR injury by activating the GAS6/Axl pathway, providing a theoretical basis for MGF as a potential cardioprotective drug in the clinical setting of myocardial IR injury.