title: Pungent ginger components modulates human cytochrome P450 enzymes in vitro.
abstract: OBJECTIVE
  Ginger rhizome is used worldwide as a spicy flavor agent. This study was designed to explore the potential effects of pungent ginger components, 6-, 8-, and 10-gingerol, on human cytochrome P450 (CYP450) enzymes that are responsible for the metabolism of many prescription drugs.
  
  
  METHODS
  The activities of human CYP2C9, CYP2C19, CYP2D6, and CYP3A4 were analyzed using Vivid P450 assay kits. The mRNA expression of CYP3A4 in human hepatocellular carcinoma cell line HepG2 was measured using quantitative real-time PCR assay.
  
  
  RESULTS
  All three gingerols potently inhibited CYP2C9 activity, exerted moderate inhibition on CYP2C19 and CYP3A4, and weak inhibion on CYP2D6. 8-Gingerol was the most potent in inhibition of P450 enzymes with IC50 values of 6.8, 12.5, 8.7, and 42.7 μmol/L for CYP2C9, CYP2C19, CYP3A4, and CYP2D6, respectively. By comparing the effects of gingerols on CYP3A4 with three different fluorescent substrate probes, it was demonstrated that the inhibition of gingerols on CYP3A4 had no substrate-dependence. In HepG2 cells, 8-gingerol and 10-gingerol inhibited, but 6-gingerol induced mRNA expression of CYP3A4.
  
  
  CONCLUSIONS
  6-, 8-, and 10-gingerol suppress human cytochrome P450 activity, while 8- and 10-gingerol inhibit CYP3A4 expression. The results may have an implication for the use of ginger or ginger products when combined with therapeutic drugs that are metabolized by cytochrome P450 enzymes.
authors.affiliation: Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences; University of the Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Mian
authors.initials: M
authors.lastname: Li
authors.forename: Pei-zhan
authors.initials: PZ
authors.lastname: Chen
authors.forename: Qing-xi
authors.initials: QX
authors.lastname: Yue
authors.forename: Jing-quan
authors.initials: JQ
authors.lastname: Li
authors.forename: Rui-ai
authors.initials: RA
authors.lastname: Chu
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
mesh_terms: D002396:Catechols / Q000494:pharmacology*; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005233:Fatty Alcohols / Q000494:pharmacology*; D020939:Zingiber officinale; D056945:Hep G2 Cells; D006801:Humans
chemical_list: D002396:Catechols; D065607:Cytochrome P-450 Enzyme Inhibitors; D005233:Fatty Alcohols; D003577:Cytochrome P-450 Enzyme System; C007845:gingerol