Protective effects of Ginkgolide B on myocardial ischemia reperfusion injury: role of the GAS6/Axl signaling pathway.

Myocardial ischemia can induce myocardial infarction, posing a severe threat to human health. Although restoration of blood and oxygen supply alleviates tissue damage and reduces infarct size, reperfusion may trigger additional injury that exacerbates myocardial structural and functional disturbances, a phenomenon termed myocardial ischemia-reperfusion injury (MIRI). Ginkgolide B (GB), a terpenoid compound extracted from Ginkgo biloba leaves, exhibits cardiovascular protective properties. This study investigates the potential anti-MIRI effects of GB, with specific emphasis on elucidating the role of the GAS6/Axl signaling pathway in its cardioprotective mechanisms. In vivo experiments demonstrated that GB improved cardiac function and serum biochemical parameters in mice, concurrently suppressing apoptosis and mitigating oxidative stress. In vitro studies further revealed that GB protected HL-1 cardiomyocytes from hypoxia-reoxygenation (HR) injury, as evidenced by enhanced cell viability, reduced apoptosis rates, decreased ROS and LDH levels, alongside upregulated expression of GAS6, Axl, Bcl2, antioxidant-related proteins, and mitochondrial function-associated proteins. Crucially, the protective effects of GB were reversed by GAS6 knockdown or genetic ablation in the HL-1 cell HR model. Collectively, this study confirms the definitive cardioprotective efficacy of GB against MIRI and delineates the critical involvement of the GAS6/Axl signaling pathway, thereby establishing a robust theoretical foundation and scientific rationale for the clinical application of GB in MIRI management.