Antithrombotic Effect of Ginkgo Biloba Extract: A Study Based on Network Pharmacological Analysis and In vivo Experiments.

BACKGROUND AND AIMS: Thrombosis is a major contributor to cardiovascular and cerebrovascular diseases. Despite the availability of anticoagulants and thrombolytic agents, their clinical use is often limited by adverse effects. Ginkgo biloba extract (GbE), a traditional herbal medicine, has shown promise in alleviating thrombosis, but its underlying mechanisms remain insufficiently understood. This study aimed to explore the antithrombotic effects and molecular mechanisms of GbE through network pharmacology and in vivo experiments. METHODS: Online databases were utilized for identifying the GbE's active components and target genes, accompanied by thrombosis-related targets. Functional enrichment analyses, including Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis, were performed. A drug-active component-target gene-signaling pathway network and a protein-protein interaction (PPI) network were constructed to determine core target genes and pathways. In vivo, a deep vein thrombosis (DVT) model was established by ligating the inferior vena cava in male Sprague-Dawley rats. Hematoxylin and eosin staining was adopted for evaluating the vascular endothelial structure. The levels of cyclic guanosine monophosphate (cGMP), prostaglandin I2 (PGI2), nitric oxide (NO), and fibrinogen (FIB) were measured, accompanied by the activated partial thromboplastin time (APTT), thrombin time (TT), and prothrombin time (PT). Western blot analysis was performed to examine the PI3K/AKT pathway-related protein expression. RESULTS: GbE comprised 27 active components with 4727 target genes and 2462 thrombosis-related targets, with 974 shared targets, including AKT1, ALB, GAPDH, TNF, and IL6, enriched in PI3K-AKT and AGE-RAGE pathways. Molecular docking indicated strong binding of GbE's main components to core targets. In vivo, GbE significantly relieved vascular lesions of DVT rats; reduced thrombotic wet weight; increased NO, cGMP, and PGI2 levels; decreased FIB; and prolonged APTT, PT, and TT (P < 0.05). Additionally, Western blot highlighted the suppressed p-PI3K/PI3K and p-AKT/AKT ratios in DVT rats. CONCLUSIONS: GbE alleviates thrombosis by increasing antithrombotic factors and reducing coagulation, potentially via downregulating the PI3K/AKT signaling. Future studies should focus on long-term clinical trials and broader animal models to further validate GbE's therapeutic potential and explore other molecular mechanisms.