Anti-Thrombotic and Metabolic Protective Effects of Ginseng in High-Fat Diet-Induced Obese Rats: In Vivo Evaluation with In Silico Mechanistic Prediction

Cardiovascular disease (CVD) is closely linked to metabolic disorders such as obesity, dyslipidemia, and hepatic steatosis. This study investigated the anti-thrombotic and metabolic effects of KoreaGinseng F Max (KGF), a standardized extract rich in ginsenosides, in high-fat diet (HFD)-induced obese rats, and complementary in silico analyses were used to explore putative molecular targets and pathways. The extract was standardized to contain 36.97 mg/g of ginsenosides Rg1, Rb1, and Rf. Male rats were administered KGF (50, 100, or 200 mg/kg) orally for six weeks. KGF significantly improved lipid profiles by reducing serum triglycerides, total cholesterol, and low-density lipoprotein (LDL) levels. Histological analysis revealed a dose-dependent reduction in hepatic steatosis and adipocyte size. Potential anti-thrombotic activity was evaluated using a FeCl3-induced carotid artery thrombosis model, with aspirin (30 mg/kg) included as a positive control. KGF200 delayed thrombus formation and produced a carotid blood flow pattern comparable to that observed in the aspirin-treated group, without significant alterations in serum ALT, AST, BUN, or creatinine levels. To further generate mechanistic hypotheses, complementary in silico analyses, including target prediction, GO/KEGG enrichment, network analysis, and molecular docking, were performed using the marker compounds. Eight overlapping genes, including STAT3, PTAFR, VEGFA, FGF2, HPSE, IL2, HSP90AA1, and LGALS3, associated with thrombotic regulation were identified. Pathway analysis suggested that PI3K–Akt signaling, calcium signaling, Th17 cell differentiation, and proteoglycan/ECM-related signaling may represent putative pathway-level mechanisms underlying the observed protective effects. Molecular docking suggested possible interactions between the marker ginsenosides and several predicted hub targets. Collectively, these findings suggest that KGF may have potential for further investigation as a natural product-derived material for improving HFD-associated metabolic and thrombotic dysfunction, while the predicted multi-target and multi-pathway effects require further experimental validation.