BACKGROUND/AIMS: To investigate the effects of emodin on concanavalin A (Con A)-induced hepatitis in mice and to elucidate its underlying molecular mechanisms. METHODS: A fulminant hepatitis model was established successfully by the intravenous administration of Con A (20 mg/kg) to male Balb/c mice. Emodin was administered to the mice by gavage before and after Con A injection. The levels of pro-inflammatory cytokines and chemokines, numbers of CD4(+) and F4/80(+) cells infiltrated into the liver, and amounts of phosphorylated p38 MAPK and NF-κB in mouse livers and RAW264.7 and EL4 cells were measured. RESULTS: Pretreatment with emodin significantly protected the animals from T cell-mediated hepatitis, as shown by the decreased elevations of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), as well as reduced hepatic necrosis. In addition, emodin pretreatment markedly reduced the intrahepatic expression of pro-inflammatory cytokines and chemokines, including tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-1β, IL-6, IL-12, inducible nitric oxide synthase (iNOS), integrin alpha M (ITGAM), chemokine (C-C motif) ligand 2 (CCL2), macrophage inflammatory protein 2 (MIP-2) and chemokine (CXC motif) receptor 2 (CXCR2). Furthermore, emodin pretreatment dramatically suppressed the numbers of CD4(+) and F4/80(+) cells infiltrating into the liver as well as the activation of p38 MAPK and NF-κB in Con A-treated mouse livers and RAW264.7 and EL4 cells. CONCLUSION: The results indicate that emodin pretreatment protects against Con A-induced liver injury in mice; these beneficial effects may occur partially through inhibition of both the infiltration of CD4(+) and F4/80(+) cells and the activation of the p38 MAPK-NF-κB pathway in CD4(+) T cells and macrophages.
BACKGROUND/AIMS: To investigate the effects of emodin on concanavalin A (Con A)-induced hepatitis in mice and to elucidate its underlying molecular mechanisms. METHODS: A fulminant hepatitis model was established successfully by the intravenous administration of Con A (20 mg/kg) to male Balb/c mice. Emodin was administered to the mice by gavage before and after Con A injection. The levels of pro-inflammatory cytokines and chemokines, numbers of CD4(+) and F4/80(+) cells infiltrated into the liver, and amounts of phosphorylated p38 MAPK and NF-κB in mouse livers and RAW264.7 and EL4 cells were measured. RESULTS: Pretreatment with emodin significantly protected the animals from T cell-mediated hepatitis, as shown by the decreased elevations of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), as well as reduced hepatic necrosis. In addition, emodin pretreatment markedly reduced the intrahepatic expression of pro-inflammatory cytokines and chemokines, including tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-1β, IL-6, IL-12, inducible nitric oxide synthase (iNOS), integrin alpha M (ITGAM), chemokine (C-C motif) ligand 2 (CCL2), macrophage inflammatory protein 2 (MIP-2) and chemokine (CXC motif) receptor 2 (CXCR2). Furthermore, emodin pretreatment dramatically suppressed the numbers of CD4(+) and F4/80(+) cells infiltrating into the liver as well as the activation of p38 MAPK and NF-κB in Con A-treated mouse livers and RAW264.7 and EL4 cells. CONCLUSION: The results indicate that emodin pretreatment protects against Con A-induced liver injury in mice; these beneficial effects may occur partially through inhibition of both the infiltration of CD4(+) and F4/80(+) cells and the activation of the p38 MAPK-NF-κB pathway in CD4(+) T cells and macrophages.
Authors: Dina S El-Agamy; Ahmed A Shaaban; Hamdi H Almaramhy; Sarah Elkablawy; Mohamed A Elkablawy Journal: Front Pharmacol Date: 2018-03-28 Impact factor: 5.810