PLoS ONE (Jan 2015)

Protective effects of astaxanthin on ConA-induced autoimmune hepatitis by the JNK/p-JNK pathway-mediated inhibition of autophagy and apoptosis.

  • Jingjing Li,
  • Yujing Xia,
  • Tong Liu,
  • Junshan Wang,
  • Weiqi Dai,
  • Fan Wang,
  • Yuanyuan Zheng,
  • Kan Chen,
  • Sainan Li,
  • Huerxidan Abudumijiti,
  • Zheng Zhou,
  • Jianrong Wang,
  • Wenxia Lu,
  • Rong Zhu,
  • Jing Yang,
  • Huawei Zhang,
  • Qin Yin,
  • Chengfen Wang,
  • Yuqing Zhou,
  • Jie Lu,
  • Yingqun Zhou,
  • Chuanyong Guo

DOI
https://doi.org/10.1371/journal.pone.0120440
Journal volume & issue
Vol. 10, no. 3
p. e0120440

Abstract

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ObjectiveAstaxanthin, 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.Materials and methodsAutoimmune 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.ResultsAstaxanthin 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.ConclusionThis 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.