Epigallocatechin-3-gallate attenuates apoptosis and autophagy in concanavalin A-induced hepatitis by inhibiting BNIP3

Drug Des Devel Ther. 2016 Feb 15:10:631-47. doi: 10.2147/DDDT.S99420. eCollection 2016.

Abstract

Background: Epigallocatechin-3-gallate (EGCG) is the most effective compound in green tea, and possesses a wide range of beneficial effects, including anti-inflammatory, antioxidant, antiobesity, and anticancer effects. In this study, we investigated the protective effects of EGCG in concanavalin A (ConA)-induced hepatitis in mice and explored the possible mechanisms involved in these effects.

Methods: Balb/C mice were injected with ConA (25 mg/kg) to induce acute autoimmune hepatitis, and EGCG (10 or 30 mg/kg) was administered orally twice daily for 10 days before ConA injection. Serum liver enzymes, proinflammatory cytokines, and other marker proteins were determined 2, 8, and 24 hours after the ConA administration.

Results: BNIP3 mediated cell apoptosis and autophagy in ConA-induced hepatitis. EGCG decreased the immunoreaction and pathological damage by reducing inflammatory factors, such as TNF-α, IL-6, IFN-γ, and IL-1β. EGCG also exhibited an antiapoptotic and antiautophagic effect by inhibiting BNIP3 via the IL-6/JAKs/STAT3 pathway.

Conclusion: EGCG attenuated liver injury in ConA-induced hepatitis by downregulating IL-6/JAKs/STAT3/BNIP3-mediated apoptosis and autophagy.

Keywords: BNIP3; EGCG; IL-6; JAKs; STAT3; apoptosis; autophagy; concanavalin A; hepatitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Autophagy / drug effects*
  • Catechin / analogs & derivatives*
  • Catechin / pharmacology
  • Chemical and Drug Induced Liver Injury / drug therapy*
  • Chemical and Drug Induced Liver Injury / pathology
  • Concanavalin A / pharmacology*
  • Cytokines / blood
  • Janus Kinase 1 / physiology
  • Janus Kinase 2 / physiology
  • Male
  • Membrane Proteins / antagonists & inhibitors*
  • Membrane Proteins / physiology
  • Mice
  • Mice, Inbred BALB C
  • Mitochondrial Proteins / antagonists & inhibitors*
  • Mitochondrial Proteins / physiology
  • STAT3 Transcription Factor / physiology
  • Signal Transduction

Substances

  • BNip3 protein, mouse
  • Cytokines
  • Membrane Proteins
  • Mitochondrial Proteins
  • STAT3 Transcription Factor
  • Stat3 protein, mouse
  • Concanavalin A
  • Catechin
  • epigallocatechin gallate
  • Jak1 protein, mouse
  • Jak2 protein, mouse
  • Janus Kinase 1
  • Janus Kinase 2