The Protective Effects of Levo-Tetrahydropalmatine on ConA-Induced Liver Injury Are via TRAF6/JNK Signaling

Mediators Inflamm. 2018 Dec 4:2018:4032484. doi: 10.1155/2018/4032484. eCollection 2018.

Abstract

Aims: Levo-tetrahydropalmatine (L-THP) is an active ingredient of Corydalis yanhusuo W. T. Wang, which has many bioactive properties. Herein, we investigated the protective effects of L-THP on concanavalin A- (ConA-) induced hepatitis in mice and explored its possible mechanisms of these effects.

Main methods: Balb/c mice were intravenously injected with 25 mg/kg ConA to generate a model of acute autoimmune hepatitis, and L-THP (20 or 40 mg/kg) was administered orally once daily for 5 d before the ConA injection. The liver enzyme levels, proinflammatory cytokine levels, and other marker protein levels were determined 2, 8, and 24 h after ConA injection.

Results: L-THP could decrease serum liver enzymes and pathological damage by reducing the release of inflammatory factors like IL-6 and TNF-α. The results of Western Blot and PCR indicated that L-THP could ameliorate liver cell apoptosis and autophagy. L-THP could suppress T lymphocyte proliferation and the production of TNF-α and IL-6 induced by ConA in a dose-dependent manner in vitro. Additionally, the protective functions of L-THP depended on downregulating TRAF6/JNK signaling. Conclusion. The present study indicated that L-THP attenuated acute liver injury in ConA-induced autoimmune hepatitis by inhibiting apoptosis and autophagy via the TRAF6/JNK pathway.

MeSH terms

  • Animals
  • Berberine Alkaloids / pharmacology*
  • Berberine Alkaloids / therapeutic use*
  • Chemical and Drug Induced Liver Injury / drug therapy*
  • Chemical and Drug Induced Liver Injury / metabolism*
  • Concanavalin A / toxicity*
  • Liver / drug effects*
  • Liver / injuries
  • Liver / metabolism*
  • MAP Kinase Kinase 4 / metabolism*
  • Male
  • Mice
  • TNF Receptor-Associated Factor 6 / metabolism*

Substances

  • Berberine Alkaloids
  • TNF Receptor-Associated Factor 6
  • Concanavalin A
  • tetrahydropalmatine
  • MAP Kinase Kinase 4