Shikonin Attenuates Concanavalin A-Induced Acute Liver Injury in Mice via Inhibition of the JNK Pathway

Mediators Inflamm. 2016:2016:2748367. doi: 10.1155/2016/2748367. Epub 2016 May 16.

Abstract

Objective: Shikonin possesses anti-inflammatory effects. However, its function in concanavalin A-induced acute liver injury remains uncertain. The aim of the present study was to investigate the functions of shikonin and its mechanism of protection on ConA-induced acute liver injury.

Materials and methods: Balb/C mice were exposed to ConA (20 mg/kg) via tail vein injection to establish acute liver injury; shikonin (7.5 mg/kg and 12.5 mg/kg) was intraperitoneally administered 2 h before the ConA injection. The serum liver enzyme levels and the inflammatory cytokine levels were determined at 3, 6, and 24 h after ConA injection.

Results: After the injection of ConA, inflammatory cytokines IL-1β, TNF-α, and IFN-γ were significantly increased. Shikonin significantly ameliorated liver injury and histopathological changes and suppressed the release of inflammatory cytokines. The expressions of Bcl-2 and Bax were markedly affected by shikonin pretreatment. LC3, Beclin-1, and p-JNK expression levels were decreased in the shikonin-pretreated groups compared with the ConA-treated groups. Shikonin attenuated ConA-induced liver injury by reducing apoptosis and autophagy through the inhibition of the JNK pathway.

Conclusion: Our results indicated that shikonin pretreatment attenuates ConA-induced acute liver injury by inhibiting apoptosis and autophagy through the suppression of the JNK pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Chemical and Drug Induced Liver Injury / drug therapy*
  • Chemical and Drug Induced Liver Injury / metabolism*
  • Concanavalin A / toxicity*
  • Immunohistochemistry
  • Interferon-gamma / metabolism
  • Interleukin-1beta / metabolism
  • Liver / drug effects
  • Liver / metabolism
  • MAP Kinase Signaling System / drug effects
  • Male
  • Mice, Inbred BALB C
  • Naphthoquinones / therapeutic use*
  • Random Allocation
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Interleukin-1beta
  • Naphthoquinones
  • Tumor Necrosis Factor-alpha
  • Concanavalin A
  • shikonin
  • Interferon-gamma