Cardiovascular diseases, as a critical global public health challenge, have drawn extensive attention due to their high prevalence and mortality rates [1]. Acute myocardial infarction, a severe acute manifestation of cardiovascular diseases, is pathologically characterized by acute coronary artery occlusion, ultimately leading to myocardial ischemia/hypoxia and cardiomyocyte necrosis [2].

Current standardized therapeutic strategies for AMI, including thrombolysis, percutaneous coronary intervention (PCI), and coronary artery bypass grafting (CABG), primarily aim to achieve myocardial reperfusion via restoration of coronary blood flow [3]. However, the reperfusion process itself may paradoxically induce myocardial ischemia-reperfusion injury (MIRI), clinically manifested as energy metabolism dysregulation, exacerbated oxidative stress, and infarct expansion [4]. The pathogenesis of MIRI involves intricate cross-talk among multiple pathological factors, including calcium overload, mitochondrial dysfunction, inflammatory cascades, and endoplasmic reticulum stress. This multifactorial complexity substantially limits the therapeutic efficacy of single-mechanism interventions [5,6].

In recent years, traditional Chinese medicine (TCM) has demonstrated unique potential in MIRI prevention and management, attributed to its multi-target effects, broad therapeutic spectrum, and favorable safety profile. Ginkgo biloba, a classical medicinal herb, exhibits multi-pathway modulation of MIRI pathogenesis through its bioactive extract [7]. The extract comprises diverse pharmacologically active constituents, including flavonoids, terpenoids, and phenolic acid derivatives [[8], [9], [10]]. Notably, Ginkgolide B (GB), the principal diterpene lactone component, demonstrates pleiotropic pharmacological properties encompassing anti-inflammatory activity, free radical scavenging, and neuroprotection. Experimental studies have validated that GB exerts cardioprotective effects by ameliorating redox imbalance and inhibiting pro-inflammatory signaling pathways [11,12]. Nevertheless, the precise molecular mechanisms underlying GB-mediated attenuation of MIRI remain to be fully elucidated.

Growth arrest-specific protein 6 (GAS6), a vitamin K-dependent secretory protein, regulates fundamental biological processes such as cell proliferation, migration, differentiation, adhesion, and apoptosis through activation of its tyrosine kinase receptor Axl [13,14]. Emerging evidence indicates that the GAS6/Axl signaling axis plays a pivotal regulatory role in the pathophysiology of CVDs, including myocardial infarction, atherosclerosis, and hypertension [[15], [16], [17]]. However, whether GB confers anti-MIRI effects via modulation of the GAS6/Axl signaling pathway necessitates systematic investigation.

This study systematically investigates the molecular mechanisms by which GB alleviates MIRI through regulation of the GAS6/Axl signaling axis, aiming to establish an innovative theoretical foundation for therapeutic interventions against cardiovascular diseases and their complications.