Effect of Oridonin on Cytochrome P450 Expression and Activities in HepaRG Cell

Pharmacology. 2018;101(5-6):246-254. doi: 10.1159/000486600. Epub 2018 Jan 26.


Oridonin, the major terpene found in Rabdosia rubescens, is widely used as a dietary supplement or therapeutic drug. However, the effects of oridonin on major CYP450s are still unclear. As oridonin can enhance the effect of other clinical drugs, in this study, we investigated the influence of oridonin on CYP450s mRNA expression and its impact on activities in human HepaRG cell to evaluate the safety by studying its potential drug interaction. HepaRG cells were cultured with series concentrations of oridonin (1, 5, 10, and 20 μmol/L), and the major CYP450s mRNA and protein expression, as well as enzyme activities were analyzed by real-time polymerase chain reaction, Western blot analysis and UPLC-MS/MS-based metabolite assay. In general, ordonin has induced effects on the major member of CYP450s mRNA and protein expression, as well as on the enzyme activity in human HepaRG cells, especially on CYP3A4 and CYP2C9. To our knowledge, this is the first systematic research about the inductive effects of oridonin on the major member of CYP450s in human cell line. These results may provide at least partly of the basis for potential drug-drug interactions and oridonin should be used with caution to avoid potential risk.

Keywords: CYP450s; Diterpenoid; Drug-drug interaction; Oridonin.

MeSH terms

  • Blotting, Western
  • Cell Line, Tumor
  • Chromatography, High Pressure Liquid
  • Cytochrome P-450 Enzyme Inducers / administration & dosage
  • Cytochrome P-450 Enzyme Inducers / pharmacology*
  • Cytochrome P-450 Enzyme System / genetics*
  • Cytochrome P-450 Enzyme System / metabolism
  • Diterpenes, Kaurane / administration & dosage
  • Diterpenes, Kaurane / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Gene Expression Regulation, Enzymologic / drug effects*
  • Humans
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Tandem Mass Spectrometry


  • Cytochrome P-450 Enzyme Inducers
  • Diterpenes, Kaurane
  • RNA, Messenger
  • oridonin
  • Cytochrome P-450 Enzyme System