Glycyrrhiza Extract Glycyrrhizic Acid The Diammonium By Il-10 Dependent Pathway To Protect Mice Of T Cell-mediated Hepatitis,

The immune constitution of liver is quite distinct from other tissue or organs, containing a large proportion of resident innate immune cells such as macrophages, NK cells and NKT cells. When the hepatic immune system becomes unbalanced, the severe inflammation will occur and lead to liver failure. Con A is a T-lymphocyte mitogen in vitro and in vivo that leads to lymphocyte proliferation and acute liver injury in mice. ConA-induced hepatitis represents an experimental model for fulminant hepatitis in mice with no other organs being affected. NKT cells, conventional T cells and macrophages appear to play crucial roles in the ConA-induced hepatitis through several different mechanisms such as those involving the Fas/FasL system, perforin/granzyme system, and IFN-γ, IL-4 and TNF-α -mediated system.Diammonium Glycyrrhizinate (DG), a Traditional Chinese Medicine (TCM), is extracted and purified from Liquorices (Radix Glycyrrhizae). The Liquorices exert an important function in treatment of hepatitis because of its anti-inflammatory effects based upon the clinical practice, but the underlying mechanism is unclear. The aim of the present study was to characterize the role of DG in preventing liver from the ConA-induced hepatitis and offer the experimental theory for clinical use.Mice received nontoxic intraperitoneal DG injection before ConA intravenous administration. The liver injury was examined by measuring serum transaminase and pathology, and the function of cytokines was detected by FACS analysis and ELISA analysis.The results showed that intraperitoneally administration of DG protected mice against ConA-induced elevation of serum ALT levels and apoptosis of hepatocytes; at the same time, the absolute amount of hepatic NKT cells and T cells were significantly decreased, indicating that DG can inhibit the recruitment of lymphocytes into liver. In addition, the production of IL-6 and IL-10 were improved by DG pretreatment, suggesting that DG may possibly protect liver from injury via three pathways: 1) direct protection of hepatocytes from apoptosis through an IL-6-dependent way; 2) indirect inhibition of T-cell-mediated inflammation through an IL-10-dependent way and 3) pretreatment of DG markedly decreased the total numbers of NKT cells and T cells in liver.