甘草黄酮通过调节AMPK/mTORC1/AKT信号网络改善2型糖尿病

The increasing global burden of type 2 diabetes mellitus (T2DM) and the limited efficacy of single-target therapies highlight the potential of multi-component interventions. Here, licorice flavonoids (LF), a multi-component extract from Glycyrrhiza uralensis, were evaluated for their antidiabetic effects and underlying mechanisms in T2DM. LF were prepared and chemically characterized by LC-MS-based profiling and quantitative analysis and their effects were assessed in high-fat, high-sugar diet/streptozotocin (HFD/STZ)-induced diabetic mice and sodium palmitate (SP)-induced insulin resistance (IR) HepG2 cells. LF markedly improved metabolic abnormalities in diabetic mice, as evidenced by reduced fasting glucose levels, improved glucose handling and insulin sensitivity, together with alleviation of dyslipidemia. In IR HepG2 cells, LF promoted glycogen synthesis, suppressed gluconeogenesis and lipogenesis, and enhanced fatty acid oxidation. Mechanistically, LF modulated the AMPK/mTORC1/AKT signaling network, as evidenced by increased AMPK and AKT phosphorylation and reduced mTORC1 activity. Pharmacological inhibition of AMPK with BAY-3827 partially attenuated LF-induced signaling changes, supporting a role for AMPK while suggesting the involvement of additional regulatory mechanisms. Collectively, these results support the potential of LF as a multi-component therapeutic strategy for T2DM and offer mechanistic insight into its beneficial effects on metabolic dysfunction through the AMPK/mTORC1/AKT signaling network.