Syringin inhibits insulin resistance through the PI3K/AKT pathway

This study aims to investigate the effects of syringin on insulin resistance (IR) and its mechanisms using an IR model in HepG2 cells. IR was induced by 10⁴ mol L^–1 insulin for 24 h, followed by syringin treatment at various concentrations for 48 h. Levels of glucose, triglycerides, TNF-α, IL-6, and GRP78 were measured, and protein expression of IRS-1, p-IRS-1, PI3K, p-PI3K, AKT, p-AKT, FoxO1, and p-FoxO1 was analysed by Western blot. Compared with controls, the IR model showed significant increases in glucose, triglycerides, TNF-α, IL-6, GRP78, and decreases in p-IRS1/IRS1, p-PI3K/PI3K, and p-AKT/AKT, with increased p-FoxO1/FoxO1 (all p < 0.01). Syringin (50–200 μg mL^–1) significantly lowered glucose, triglycerides, TNF-α, IL-6, and GRP78, and reversed these signalling changes by upregulating p-IRS1/IRS1, p-PI3K/PI3K, p-AKT/AKT and downregulating p-FoxO1/FoxO1 (p < 0.05). Syringin effectively ameliorates insulin resistance in HepG2 cells, lowers glucose and triglycerides, and improves glucose-lipid metabolism, likely via the PI3K/AKT pathway.