Abstract
Ischemia/reperfusion (I/R) injury causes myocardial damage, and Ginkgolide C (GC), a component of Ginkgo biloba, shows potential for cardioprotection. However, its effects on I/R-induced cardiac dysfunction and mechanisms are unclear. This study evaluates GC preconditioning in rats, focusing on its impact on cardiac function, myocardial injury, and the PI3K/Akt pathway. GC preconditioning was assessed using an isolated rat heart model of I/R injury. Cardiac function (LVDP, LVEDP, +dp/dtmax, -dp/dtmax), infarct size, histopathological changes, injury, and oxidative stress markers were measured. Rat cardiomyocytes were treated with GC to assess viability, contraction, and apoptosis. Molecular docking and protein analysis explored GC's interaction with the Akt pathway. GC preconditioning significantly improved cardiac function, with a marked enhancement in LVDP, +dp/dtmax, and -dp/dtmax in the GC50 group compared to the I/R group (P<0.01). GC treatment also reduced myocardial infarct size (14.8 %±2.4 % vs. 25.5 %±1.9 %, P<0.01), decreased LDH release, and alleviated histopathological damage, including myocyte necrosis and inflammatory infiltration. Furthermore, GC significantly improved cardiomyocyte viability and contraction amplitude, particularly at 50 ?M. At the molecular level, GC activated the Akt pathway, as evidenced by increased p-Akt expression. Co-treatment with the PI3K inhibitor LY294002 reversed the protective effects of GC, confirming the involvement of the Akt pathway. Additionally, GC preconditioning reduced oxidative stress, as indicated by enhanced SOD activity and decreased levels of myocardial injury markers (LDH, CK-MB), and decreased apoptosis, reflected by a lower Bax/Bcl-2 ratio. GC preconditioning reduces I/R-induced myocardial injury in rats by activating the PI3K/Akt pathway, reducing oxidative stress, inhibiting apoptosis, and improving cell viability. These results support GC's potential for treating ischemic heart disease and suggest Akt-targeted interventions for myocardial protection. Keywords Ginkgolide C " Ischemia/reperfusion injury " Cardioprotection " PI3K/Akt pathway.