Glycyrrhizin prevents of lipopolysaccharide/D‐galactosamine‐induced liver injury through down‐regulation of matrix metalloproteinase‐9 in mice

Abe, Kazuki; Ikeda, Tadayuki; Wake, Kenjiro; Sato, Tetsuji; Sato, Toshitsugu; Inoue, Hideo

Glycyrrhizin, a biological active compound isolated from the liquorice root, has been used as a treatment for chronic hepatitis. We have examined the involvement of matrix metalloproteinase (MMP)‐9 in the development of lipopolysaccharide (LPS) and D‐galactosamine (GalN)‐induced liver injury in mice. We also investigated the effect of glycyrrhizin on expression of MMP‐9 in this model. Levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) increased after LPS/GalN treatment. Expression of MMP‐9 mRNA and protein was markedly up‐regulated in liver tissues 6–8 h after LPS/GalN treatment. Pretreatment with glycyrrhizin (50 mg kg(−1)) and the MMP inhibitor (5 mg kg(−1)) suppressed increases in serum levels of ALT and AST in mice treated with LPS/GalN. Furthermore, glycyrrhizin inhibited levels of both mRNA and protein for MMP‐9. Immunohistochemical reaction for MMP‐9 was observed in macrophages/monocytes infiltrated in the inflammatory area of liver injury. Glycyrrhizin reduced the infiltration of inflammatory cells and immunoreactive MMP‐9 in liver injury. The results indicated that MMP‐9 played a role in the development of LPS/GalN‐induced mouse liver injury, and suggested that an inhibition by glycyrrhizin of the acute liver injury may have been due to a down‐regulation of MMP‐9.