Protective effects of Gnetum montanum extract against oleic acid-induced lipotoxicity in hepatocytes

Hepatic lipid accumulation plays a key role in the early stages of fatty liver disease and can lead to liver cell dysfunction and damage. Although Gnetum montanum has demonstrated antioxidant and metabolic regulatory effects, its role in lipid metabolism pathways is not yet fully understood. This study aimed to investigate whether G. montanum extract (GME) exerts protective effects against lipid accumulation and lipotoxicity. We found that treating HepG2 cells with oleic acid (OA) induced significant intracellular lipid accumulation, as evidenced by the presence of lipid droplets, which was assessed via Oil Red O and BODIPY 493/503 staining, and an increase in intracellular triglyceride levels. OA exposure also triggered oxidative stress, cell membrane damage, and apoptosis. Pretreatment with GME at concentrations of 3 and 10 µg/mL significantly reduced OA-induced lipid droplet formation and intracellular triglyceride levels. Additionally, GME effectively attenuated malondialdehyde (MDA) levels, reduced the release of hepatic enzymes aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and inhibited caspase-3 nuclear translocation and cell apoptosis. These effects were comparable to those of silibinin (SIL), a well-established positive control. In summary, these findings suggest that GME may possess promising anti-lipid accumulation and hepatoprotective properties