Mechanism of Ginkgo Diterpene Lactone Meglumine Injection Promoting Angiogenesis and Improving Cerebral Perfusion in Cerebral Infarction Rats

Background In recent years, traditional Chinese medicine has shown advantages in treating ischemic cerebrovascular diseases, including multi-component, multi-target, and low toxicity effects. Objectives The aim of this study was to clarify the impact of ginkgo diterpene lactone meglumine injection (GDLMI) on promoting microvascular neovascularization and improving cerebral perfusion after cerebral infarction (CIF) in rats and to explore its underlying mechanisms in promoting angiogenesis. Materials and Methods Seventy-five rats were randomly rolled into Sham (sham surgery) group, Model (acute CIF model) group, low-dose (LD) (1 g/kg bw GDLMI) group, medium-dose (MD) (3 g/kg bw GDLMI) group, and high-dose (HD) (5 g/kg bw GDLMI) group. The neurological function of rats was evaluated using the Longa method. Micro-PET was performed to evaluate brain metabolism status at 7 days post-reperfusion. Serum expression levels (ELs) of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α were measured. Brain tissue samples were collected to assess cerebral infarct volume and to measure oxidative stress (OS) markers, including superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA). TdT-mediated dUTP nick end labeling (TUNEL) was performed to detect the apoptosis rate of cortical neurons. Western blotting was conducted to determine brain tissue’s ELs of vascular endothelial growth factor (VEGF), angiopoietins-1 (Ang-1), p-PI3K, and p-AKT proteins. Results Rats in Model group exhibited higher Longa scores and increased cerebral infarct volume, decreased brain 18 F-FDG content, elevated serum ELs of IL-1β, IL-6, and TNF-α, reduced SOD and CAT activities, increased MDA content in brain tissue, elevated apoptosis rate of cortical neurons, and elevated protein ELs of VEGF and Ang-1 in brain tissue, accompanied by decreased ELs of p-PI3K and p-AKT proteins compared to the Sham group ( p < 0.05). Rats in the LD, MD, and HD groups showed decreased Longa scores and cerebral infarct volume, increased brain 18 F-FDG content, decreased ELs of IL-1β, IL-6, and TNF-α, increased SOD and CAT activities, decreased MDA content in brain tissue, decreased apoptosis rate of cortical neurons, and increased protein ELs of VEGF, Ang-1, p-PI3K, and p-AKT in brain tissue versus Model group ( p < 0.05). The effects on all indicators in rats showed a dose-dependent trend. Conclusion GDLMI has a protective effect against acute CIF/reperfusion injury (RI), which may be attributed to its ability to suppress inflammation and OS damage by activating PI3K/AKT signaling.