Arctiin Antagonizes Triptolide-Induced Hepatotoxicity via Activation of Nrf2 Pathway

Biomed Res Int. 2020 Oct 16:2020:2508952. doi: 10.1155/2020/2508952. eCollection 2020.

Abstract

Triptolide (TP) is the most effective ingredient found in the traditional Chinese herbal Tripterygium wilfordii Hook F, and it is widely used in therapies of autoimmune and inflammatory disorders. However, the hepatotoxicity induced by TP has restricted its use in clinical trials. Arctiin is known as a protective agent against oxidative stress, and it exerts liver-protecting effect. This study was aimed at investigating the protective role of arctiin against TP-induced hepatotoxicity using in vitro and in vivo models. The results indicated that TP not only obviously induced liver injury in mice but also significantly inhibited the growth of HepG2 cells and increased the level of intracellular reactive oxygen. Furthermore, TP obviously decreased the expressions of proteins of Nrf2 pathway including HO-1, NQO1, and Nrf2 associated with oxidative stress pathway. However, the above experimental indexes were reversed by the treatment of arctiin. Our results suggested that arctiin could alleviate TP-induced hepatotoxicity, and the molecular mechanism is likely related to its capacity against oxidative stress.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Chemical and Drug Induced Liver Injury / drug therapy*
  • Chemical and Drug Induced Liver Injury / metabolism*
  • Diterpenes / adverse effects*
  • Epoxy Compounds / adverse effects
  • Furans / pharmacology*
  • Glucosides / pharmacology*
  • Hep G2 Cells
  • Humans
  • Liver / drug effects*
  • Liver / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • NF-E2-Related Factor 2 / metabolism*
  • Oxidative Stress / drug effects
  • Phenanthrenes / adverse effects*
  • Protective Agents / pharmacology
  • Signal Transduction / drug effects

Substances

  • Diterpenes
  • Epoxy Compounds
  • Furans
  • Glucosides
  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • Phenanthrenes
  • Protective Agents
  • triptolide
  • arctiin