Abstract: Objective: To explore the protective effect of arctigenin (ATG) on liver injury in diabetic mice. Methods: Alloxan was used to induce diabetes in male ICR mice. Six groups of mice were set up: control, model, positive control (metformin, Met), and high-, medium-, and low-dose ATG (120, 90 and 60 mg/kg mb). The activities of alanine aminotransferase (ALT) and asparate aminotransferase (AST) and the concentrations of the inflammatory cytokine interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were in the serum determined. Liver glutathione (GSH), catalase (CAT) and superoxide dismutase (SOD) levels were analyzed, and histomorphological observation of the liver was performed after hematoxylin and eosin staining. Protein expression levels involved in the toll-like receptors (TLR4), myeloid differentiation factor 88 (MyD88) and nuclear factor κB p65 (NF-κB p65) signaling pathways were measured. Results: Compared with the model group, high-dose ATG significantly reduced ALT and AST activities in the serum of diabetic mice (P < 0.01); high- and medium-dose ATG significantly reduced serum IL-6 and TNF-α levels (P < 0.01); high-dose ATG significantly increased liver CAT and SOD activities (P < 0.01) as well as GSH levels (P < 0.05); high- and medium-dose ATG significantly improved the cellular morphology of liver tissue, increasing the red-stained area of cells in liver slices and reducing cell vacuoles and bleeding areas. High-dose ATG significantly reduced the protein expression of TLR4, MyD88 and NF-κB p65 in the liver (P < 0.01 and P < 0.05). The hepatoprotective mechanism of ATG may be related to reducing the expression of key proteins in the TLR4, MyD88 and NF-κB p65 signaling pathways, and inhibiting the expression of downstream inflammatory factors, such as NF-κB, TNF-α and IL-6, thereby reducing the level of oxidative stress. Conclusion: ATG has a protective effect on diabetic liver injury. This study provides a reference for the application of ATG in the prevention and treatment of diabetic liver injury.

Key words: arctigenin; diabetes; liver injury; protective effect; mechanism of action