Arginyl-Fructosyl-Glucose Derived from Korean Red Ginseng Attenuates Methylglyoxal-Induced Insulin Resistance in HepG2 Cells.

In the present study, we investigated the protective effects of arginyl-fructosyl-glucose (AFG), a major Maillard reaction product naturally formed during red ginseng processing, against methylglyoxal (MG)-induced insulin resistance in HepG2 cells. HepG2 cells were exposed to 1 mM MG to induce insulin resistance, and co-treated with various concentrations of AFG. Glucose uptake, intracellular ROS, and the expression of insulin- and antioxidant-related proteins were evaluated. AFG exhibited no cytotoxicity at concentrations ranging from 6.25 to 200 µM. In the 2-NBDG glucose uptake assay, treatment with 1 mM MG markedly reduced glucose uptake and induced insulin resistance, whereas co-treatment with AFG significantly improved glucose uptake. Moreover, DCFH-DA fluorescence analysis showed that AFG attenuated MG-induced oxidative stress. Western blot analysis further revealed that AFG upregulated SIRT1, PI3K, and PPARγ expression, leading to Akt phosphorylation, GLUT2 translocation to the cell membrane, and Nrf2 nuclear translocation. In addition, AFG suppressed TNF-α expression, thereby mitigating MG-induced oxidative damage. Collectively, these findings suggest that AFG, a bioactive component of Korean red ginseng, alleviates oxidative stress and improves glucose metabolism in MG-exposed HepG2 cells, highlighting its potential as a functional food ingredient for supporting metabolic health.