title: Protective effects of astaxanthin on ConA-induced autoimmune hepatitis by the JNK/p-JNK pathway-mediated inhibition of autophagy and apoptosis.
abstract: OBJECTIVE
  Astaxanthin, a potent antioxidant, exhibits a wide range of biological activities, including antioxidant, atherosclerosis and antitumor activities. However, its effect on concanavalin A (ConA)-induced autoimmune hepatitis remains unclear. The aim of this study was to investigate the protective effects of astaxanthin on ConA-induced hepatitis in mice, and to elucidate the mechanisms of regulation.
  
  
  METHODS
  Autoimmune hepatitis was induced in in Balb/C mice using ConA (25 mg/kg), and astaxanthin was orally administered daily at two doses (20 mg/kg and 40 mg/kg) for 14 days before ConA injection. Levels of serum liver enzymes and the histopathology of inflammatory cytokines and other maker proteins were determined at three time points (2, 8 and 24 h). Primary hepatocytes were pretreated with astaxanthin (80 μM) in vitro 24 h before stimulation with TNF-α (10 ng/ml). The apoptosis rate and related protein expression were determined 24 h after the administration of TNF-α.
  
  
  RESULTS
  Astaxanthin attenuated serum liver enzymes and pathological damage by reducing the release of inflammatory factors. It performed anti-apoptotic effects via the descending phosphorylation of Bcl-2 through the down-regulation of the JNK/p-JNK pathway.
  
  
  CONCLUSIONS
  This research firstly expounded that astaxanthin reduced immune liver injury in ConA-induced autoimmune hepatitis. The mode of action appears to be downregulation of JNK/p-JNK-mediated apoptosis and autophagy.
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China.
authors.forename: Yujing
authors.initials: Y
authors.lastname: Xia
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China.
authors.forename: Junshan
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China.
authors.forename: Weiqi
authors.initials: W
authors.lastname: Dai
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China.
authors.forename: Kan
authors.initials: K
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China.
authors.forename: Sainan
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China.
authors.forename: Huerxidan
authors.initials: H
authors.lastname: Abudumijiti
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, The First Clinical Medical College of Nanjing Medical University, Nanjing, 210029, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, The First Clinical Medical College of Nanjing Medical University, Nanjing, 210029, China.
authors.forename: Jianrong
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, The First Clinical Medical College of Nanjing Medical University, Nanjing, 210029, China.
authors.forename: Wenxia
authors.initials: W
authors.lastname: Lu
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, The First Clinical Medical College of Nanjing Medical University, Nanjing, 210029, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Zhu
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Soochow University, Suzhou, 215006, China.
authors.forename: Huawei
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Soochow University, Suzhou, 215006, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Yin
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China.
authors.forename: Chengfen
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Soochow University, Suzhou, 215006, China.
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Lu
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China.
authors.forename: Yingqun
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China.
authors.forename: Chuanyong
authors.initials: C
authors.lastname: Guo
mesh_terms: D000284:Administration, Oral; D000818:Animals; D017209:Apoptosis; D001343:Autophagy / Q000187:drug effects; D002478:Cells, Cultured; D003208:Concanavalin A / Q000008:administration & dosage* / Q000633:toxicity; D016207:Cytokines / Q000378:metabolism; D004334:Drug Administration Schedule; D019693:Hepatitis, Autoimmune / Q000201:enzymology / Q000276:immunology / Q000517:prevention & control*; D022781:Hepatocytes / Q000187:drug effects*; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D024341:Xanthophylls / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D016207:Cytokines; D024341:Xanthophylls; D003208:Concanavalin A; C005948:astaxanthine