Gegen Qinlian Decoction inhibits liver ferroptosis in type 2 diabetes mellitus models by targeting Nrf2

Ethnopharmacological relevance: Type 2 diabetes mellitus (T2DM) is a metabolic disease that can lead to complications affecting multiple organs, including the liver. Gegen Qinlian Decoction (GQD) has demonstrated considerable efficacy in the management of T2DM and its complications in accordance with the tenets of modern Chinese medicine. However, the molecular mechanism by which GQD alleviates diabetic liver injury is unclear.

Aim of the study: To explore the effect and mechanism of GQD to ameliorate liver injury in T2DM.

Materials and methods: The active constituents of GQD were analyzed using UPLC. An in vivo T2DM mouse model was established by 6 weeks of high-fat diet and multiple streptozotocin (50 mg/kg/day) induction, followed by GQD administration. The evaluation of liver function, histopathology, oxidative stress, lipid peroxidation, and iron levels was conducted. In vitro experiments involved a high-glucose-induced AML12 cell model to assess oxidative stress, lipid peroxidation, and iron levels.

Results: UPLC identified four main components in GQD: puerarin, baicalin, berberine and liquiritin. GQD administration resulted in enhanced liver function and a reduction in injury, accompanied by elevated antioxidant enzyme activity, increased GPX4 expression and diminished reactive oxygen species in T2DM mice. GQD treatment reduced lipid peroxidation and regulated iron transport proteins, thereby alleviating iron overload. In AML12 cells, GQD administration resulted in regulated mitochondrial morphology.

Conclusion: Our findings demonstrated that GQD ameliorated liver injury in T2DM by inhibiting ferroptosis through the modulation of Nrf2.