Protective effect of aescin from the seeds of Aesculus hippocastanum on liver injury induced by endotoxin in mice

To investigate the effect and underlying mechanism of aescin on acute liver injury induced by endotoxin, liver injury was established by injecting lipopolysaccharide (LPS) in mice. Animals were assigned to seven groups: the control group and groups treated with LPS (40 mg/kg), aescin (3.6 mg/kg), LPS plus dexamethasone (4 mg/kg) and LPS plus aescin (0.9, 1.8 or 3.6 mg/kg). Hepatic histopathological changes were examined under a light microscope. Activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum were determined. Levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), nitric oxide (NO) and antioxidative parameters in liver homogenate were measured. Glucocorticoid receptor (GR), 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1) and 11 beta-hydroxysteroid dehydrogenase type 2 (11 beta-HSD2) expressions in liver were determined by western blotting. Treatment with escin could inhibit immigration of inflammatory cells, alleviate the degree of necrosis, and decrease serum ALT and AST activities. Aescin also down-regulated levels of inflammation mediators (TNF-alpha, IL-1 beta and NO) and 11 beta-HSD2 expression in liver, up-regulated GR expression, enhanced endogenous antioxidative capacity, but have no obvious effect on 11 beta-HSD1 expression in liver. The findings suggest aescin has protective effects on endotoxin-induced liver injury, and the underlying mechanisms were associated with its anti-inflammatory effects, up-regulating GR expression, down-regulating 11 beta-HSD2 experssion, and antixoidation. (C) 2011 Elsevier GmbH. All rights reserved.