Mung bean seed coat water extract restores insulin sensitivity via upregulation of antioxidant defense system and downregulation of inflammation in insulin-resistant HepG2 cells

Insulin resistance is the main cause of type 2 diabetes. Mung bean possesses many health benefits mainly related to polyphenols, which is abundant in mung bean seed coat. Total phenolic content in mung bean seed coat water extract (MSWE) was 0.62 ± 0.00 mg gallic acid equivalents (GAE)/g extract with antioxidant activity (IC₅₀ = 0.16 ± 0.01 mg/mL). Vitexin and isovitexin were the major flavonoids in MSWE. MSWE increased cellular glucose uptake and reduced intracellular reactive oxygen species (ROS) in insulin-resistant HepG2 cells. MSWE upregulated IRS-1, FGFR1, PI3K, and AKT expression, while downregulated FOXO1, PEPCK, and GSK3. MSWE modulated the expression of antioxidant genes including NRF2, KEAP1, HO-1, and NQO1. MSWE also downregulated genes related to inflammation (IL-6, IL-1β, TNF-α, PTP1B, and p53). In conclusion, MSWE restored insulin sensitivity possibly through the reduction of ROS-associated inflammation by regulating GSK3/NRF2/KEAP1, downregulating PTP-1B and p53, as well as upregulating IRS-1/FGFR1/PI3K/AKT in insulin-resistant HepG2 cells.