Lipidomics-Based Investigation of the Effects of Ginsenoside FI on Free Fatty Acid-Induced Metabolism in HepG2 Cells

Objective: This study investigated the effects of ginsenoside F1 on lipid metabolism using cell-based assays combined with lipidomics. Methods: The optimal non-cytotoxic concentration of ginsenoside F1 was determined by the CCK-8 assay. A hyperlipidemic cell model was established by inducing HepG2 cells with free fatty acids (FFAs). Model cells were treated with ginsenoside F1 (0.2 µM, 0.8 µM, and 3.2 µM) or simvastatin (3.2 µM, positive control) for 24 h. Intracellular lipid accumulation was determined by measuring absorbance at 510 nm, together with quantification of total cholesterol (TC) and triglyceride (TG) contents. Untargeted lipidomics was employed to explore alterations in the lipid profile and identify relevant metabolic pathways. Results: Compared with the model group, lipid deposition, total cholesterol, and triglycerides were significantly reduced by ginsenoside F1 (p < 0.05). A total of 110 differential metabolites, mainly phosphatidylinositol and phosphatidylcholines, were identified by lipidomics, with glycerophospholipid and ether lipid metabolism highlighted as the key regulated pathways. Potential roles of targets including Akt1, PPARG, and EGFR, as well as pathways related to cancer and lipid metabolism, were further indicated by network pharmacology and molecular docking. Conclusions: FFA-induced lipid disorders in HepG2 cells were alleviated by ginsenoside F1, potentially through the regulation of glycerophospholipid metabolism.