Mechanism of maslinic acid of reducing the inflammatory reaction and oxidative stress in acute liver injury in mice

Objective To study the protective effect and mechanism of maslinic acid (MA) on acute liver injury (ALI) in rats. Methods Fifty BALB/c mice were randomly divided into control group, model group, and low (12.5 mg/kg), medium (25.0 mg/kg) and high doses (50.0 mg/kg) of MA, with 10 rats in each group. The control group was intraperitoneally injected with normal saline. The other groups were intraperitoneally injected with lipopolysaccharide (LPS) (50 mg/kg) and D-Gal N (500 mg/kg) to prepare mouse ALI model. The MA groups were administered with 12.5, 25.0, 50.0 mg/kg MA 1 h before model establishment, respectively. All the mice were sacrificed 6 h after model establishment, and serum and liver tissues were collected. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured. Hematoxylin-eosin staining was used to observe the pathological changes of liver tissue. Thiobarbituric acid method was used to determine malondialdehyde (MDA). H2O2 reaction product colorimetric was used to determine the content of myeloperoxidase (MPO). The tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) in serum and liver tissue was detected by enzyme-linked immunosor- bent assay, respectively. Western Blot was conducted to detect the expression of nuclear factor E2 related factor 2 (Nrf2), heme oxygenase-1 (HO-1) and the activation of nuclear factor-kappa B (NF-κB) pathway. Results Compared with the model group, the liver histopathology in the low, medium and high doses MA groups was significantly improved. The serum ALT and AST levels were decreased, and the differences were statistically significant (all P<0.05). The contents of MDA and MPO in liver tissues were decreased, and the differences were statistically significant (all P<0.05). The protein contents of Nrf2 and HO-1 were increased, the differences were statistically significant (all P<0.05). The NF-κB pathway was inhibited, and the differences were statistically significant (all P<0.05). The levels of TNF-α and IL-6 in serum and liver tissues were decreased, and the differences were statistically significant (all P<0.05). Conclusions MA has a protective effect on LPS/D-Gal N-induced ALI, and its mechanism is related to inhibition of NF-κB pathway and activation of Nrf2/HO-1 pathway. Key words: Maslinic acid; Acute liver injury; Lipopolysaccharide; D-galactosamine; Nuclear factor erythroid 2-related factor 2