Bavachinin Induces Oxidative Damage in HepaRG Cells through p38/JNK MAPK Pathways

Toxins (Basel). 2018 Apr 12;10(4):154. doi: 10.3390/toxins10040154.

Abstract

Drug-induced liver injury is one of the main causes of drug non-approval and drug withdrawal by the Food and Drug Administration (FDA). Bavachinin (BVC) is a natural product derived from the fruit of the traditional Chinese herb Fructus Psoraleae (FP). There have been reports of acute liver injury following the administration of FP and its related proprietary medicines. To explore BVC hepatotoxicity and its mechanisms, we used the HepaRG cell line. In our recent research, we showed that BVC induces HepaRG cell death, mainly via BVC-induced oxidative damage. The formation of ROS is closely related to the activation of the stress-activated kinases, JNK and p38, while SP600125 (SP, JNK inhibitor) and SB203580 (SB, p38 inhibitor) pretreatment inhibited the generation of ROS. On the other hand, N-acetylcysteine (NAC) pretreatment prevented the phosphorylation of p38 but not that of JNK. Taken together, these data reveal that BVC induces HepaRG cell death via ROS and the JNK/p38 signaling pathways.

Keywords: Bavachinin; JNK MAPK; drug-induced liver injury; p38 MAPK; reactive oxygen species.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Flavonoids / toxicity*
  • Humans
  • JNK Mitogen-Activated Protein Kinases / metabolism*
  • MAP Kinase Signaling System / drug effects
  • Oxidative Stress / drug effects
  • Reactive Oxygen Species / metabolism
  • p38 Mitogen-Activated Protein Kinases / metabolism*

Substances

  • Flavonoids
  • Reactive Oxygen Species
  • bavachinin
  • JNK Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases