Objective:To explore the protective effect of emodin on D-galactosamine (D-GalN)/lipopolysaccharide (LPS)-induced acute liver injury and its mechanism.Methods:A total of 40 male BALB/c mice were randomly (random number) divided into 5 groups ( n=8 in each group): the control group, the emodin group, the D-GalN/LPS group, the emodin+D-GalN/LPS group and the 3-MA+emodin+D-GalN/LPS group. D-GalN (700 mg/kg) and LPS (10 μg/kg) were intraperitoneally injected to induce acute liver injury in mice. Autophagy inhibitor 3-MA (15 mg/kg) and/or emodin (20 mg/kg) were intraperitoneally injected 30 min before the liver injury model. The animals were sacrificed under anaesthesia 6 h after D-GalN/LPS challenge, blood samples and liver tissues were collected. The levels of alanineaminotransferase (ALT) and aspartateaminotransferase (AST) in serum, and myeloperoxidase (MPO) activity of liver tissues were determined by colorimetric quantitative method; the levels of tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were measured by ELISA; the expression of LC3-II and Beclin 1 in the liver tissues were evaluated by Western blot; the pathological changes of liver was evaluated by HE staining. Animal survival rate was also analyzed. The one-way ANOVA was use to compare quantitative data, SNK- q test was used for pairwise comparison between two groups, and Games-Howell test was used when homogeneity of variance were not met. Results:Compared with the control group, the levels of ALT, AST, TNF-α, IL-6 and MPO activity [(2 476.80 ± 263.14) U/L, (271.71 ± 47.15) U/L, (537.92 ± 89.35) pg/mL, (169.74 ± 25.52) pg/mL, and (1.37 ± 0.22) U/mg] were obviously increased in the D-GalN/LPS group ( P<0.05). Compared with the D-GalN/LPS group, the levels of ALT, AST, TNF-α, IL-6 and MPO activity [(1 248.01 ± 380.70) U/L, (142.59 ± 34.63) U/L, (288.91 ± 67.21) pg/mL, (61.83 ± 13.64) pg/mL, and (0.80 ± 0.21) U/mg] were obviously decreased in the emodin+ D-GalN/LPS group ( P<0.05). Compared with the D-GalN/LPS group, the histopathological abnormalities in liver tissue were significantly alleviated and the survival rate of mice was improved in the emodin+ D-GalN/LPS group. Compared with the control group, the expression of LC3-II and Beclin1 was decreased in the liver tissue in the D-GalN/LPS group, while compared with the D-GalN/LPS group, the expression of LC3-II and Beclin1 was increased in the emodin+ D-GalN/LPS group. With co-administration of 3-MA, the protective effects of emodin in acute liver injury were reversed, the levels of AST, ALT, TNF-α, IL-6, and MPO [(2 398.78 ± 233.57) U/L, (242.79 ± 43.46) U/L, (505.07 ± 67.89) pg/mL, (151.46 ± 14.11) pg/mL, and (1.27 ± 0.15) U/mg] were increased, and the pathological damage of liver tissue was aggravated. Conclusions:Emodin alleviates D-GalN/LPS-induced acute liver injury in mice, which may be related to the activation of protein LC3-II, Beclin1 and restored autophagy.