The effects of
glycyrrhizin isolated from licorice root were investigated on acute
hepatitis induced by
lipopolysaccharide (LPS) and d-
galactosamine in mice. Serum
alanine aminotransferase (ALT) activity was markedly increased 6 h to 8 h after administration of LPS/d-
galactosamine. Levels in serum of
cytokines such as
tumor necrosis factor (
TNF)-alpha,
interleukin (IL)-6,
IL-10 and
IL-12 reached a maximum by 2 h, whereas levels of
IL-18, as well as of ALT, were maximal at 8 h.
Glycyrrhizin (ED(50): 14.3 mg/kg) inhibited the increase in ALT levels when it was given to mice at 30 min before administration of LPS/d-
galactosamine. Inflammatory responses, including infiltration of neutrophils and macrophages in the liver injury, were modulated by
glycyrrhizin. Increases in ALT levels were reduced by an administration of
glycyrrhizin at 10 min and 60 min but not 3 h, even after LPS/d-
galactosamine treatment. However,
glycyrrhizin had no effect on the production of
TNF-alpha,
IL-6,
IL-10 and
IL-12, whereas it significantly inhibited
IL-18 production. Exogenous
IL-18 further increased the elevation in ALT levels in mice treated with LPS/d-
galactosamine.
Glycyrrhizin completely suppressed the effect of
IL-18 of increasing ALT levels.
IL-18 was detected by immunohistochemistry in inflammatory cells such neutrophils and macrophages in liver injury.
Glycyrrhizin reduced the responsiveness of cells to
IL-18 in the liver injury. These results suggest that
glycyrrhizin inhibits the LPS/d-
galactosamine-induced liver injury through preventing inflammatory responses and
IL-18 production. Furthermore, it seems that
glycyrrhizin prevents IL-18-mediated
inflammation in liver injury.