IngentaConnect Glycyrrhizin prevents of lipopolysaccharide/D-galactosamine-induc...

Authors: Abe, Kazuki¹; Ikeda, Tadayuki²; Wake, Kenjiro³; Sato, Tetsuji²; Sato, Toshitsugu¹; Inoue, Hideo¹

Source: Journal of Pharmacy and Pharmacology, Volume 60, Number 1, January 2008 , pp. 91-97(7)

Abstract:

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.

Document Type: Research article

DOI: 10.1211/jpp.60.1.0012

Affiliations: 1: Pharmacological Research Department, Minophagen Pharmaceutical Co., 2-2-3, Komatsubara, Zama-shi, Kanagawa 228-0002, Japan 2: Department of Anatomy II, School of Dental Medicine, Tsurumi University, 2-1-3 Tsurumi, Tsurumi-ku, Yokohama, Kanagawa 230-8501, Japan 3: Department of Anatomy II, School of Dental Medicine, Tsurumi University, 2-1-3 Tsurumi, Tsurumi-ku, Yokohama, Kanagawa 230-8501, Japan; Liver Research Unit, Minophagen pharmaceutical Co., 8-10-22, Akasaka, Minato-ku, Tokyo 107-0052, Japan

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