title: Emodin protects against concanavalin A-induced hepatitis in mice through inhibiting activation of the p38 MAPK-NF-κB signaling pathway.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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: State Key Lab of Diagnostic and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Disease, 1st Affiliated Hospital of Medical School, Zhejiang University, Hangzhou, China.
authors: Jihua
authors: J
authors: Xue
authors: Feng
authors: F
authors: Chen
authors: Jing
authors: J
authors: Wang
authors: Shanshan
authors: S
authors: Wu
authors: Min
authors: M
authors: Zheng
authors: Haihong
authors: H
authors: Zhu
authors: Yanning
authors: Y
authors: Liu
authors: Jiliang
authors: J
authors: He
authors: Zhi
authors: Z
authors: Chen
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D039481:CD11b Antigen / Q000235:genetics / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002460:Cell Line; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D003208:Concanavalin A / Q000276:immunology / Q000633:toxicity; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004642:Emodin / Q000494:pharmacology*; D006505:Hepatitis / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D020011:Protective Agents / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D039481:CD11b Antigen; D018925:Chemokines; D016207:Cytokines; D016328:NF-kappa B; D020011:Protective Agents; D003208:Concanavalin A; D052247:Nitric Oxide Synthase Type II; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D048051:p38 Mitogen-Activated Protein Kinases; D004642:Emodin