Effects of capsaicin and dihydrocapsaicin on human and rat liver microsomal CYP450 enzyme activities in vitro and in vivo

J Asian Nat Prod Res. 2012;14(4):382-95. doi: 10.1080/10286020.2012.656605.


Capsaicin and dihydrocapsaicin, the two most abundant members of capsaicinoids in chili peppers, are widely used as food additives and for other purposes. In this study, we examined the inhibitory potentials of capsaicin and dihydrocapsaicin against CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4/5 activities in human liver microsomes. The effects of these two capsaicinoids on CYP450 enzymes were also evaluated in vivo in rats. The results demonstrated that capsaicin and dihydrocapsaicin moderately inhibited five isozymes (IC₅₀) values ranging from 4.4 to 61.8 μM), with the exception of CYP2E1 (IC₅₀ > 200 μM). Both capsaicinoids exhibited competitive, mixed, and noncompetitive inhibition on these isozymes (K (i) = 3.1 ± 0.5 - 78.6 ± 8.4 μM). Time-dependent inhibition of CYP3A4/5 by capsaicin was found. After multiple administrations of capsaicin and dihydrocapsaicin (1, 4, and 10 mg/kg) to rats, chlorzoxazone 6-hydroxylase activity and the expression of CYP2E1 were increased in liver microsomes. Our findings indicated that the possibility of food-drug interactions mediated by capsaicin and dihydrocapsaicin could not be excluded, and provided the useful information for evaluating the anticarcinogenic potentials of these two capsaicinoids.

MeSH terms

  • Animals
  • Aryl Hydrocarbon Hydroxylases / antagonists & inhibitors
  • Aryl Hydrocarbon Hydroxylases / drug effects
  • Capsaicin* / administration & dosage
  • Capsaicin* / analogs & derivatives
  • Capsaicin* / chemistry
  • Capsaicin* / pharmacology
  • Cytochrome P-450 CYP1A2 Inhibitors
  • Cytochrome P-450 CYP2C19
  • Cytochrome P-450 CYP2E1 / drug effects
  • Cytochrome P-450 CYP2E1 Inhibitors
  • Cytochrome P-450 CYP3A Inhibitors*
  • Dose-Response Relationship, Drug
  • Food-Drug Interactions
  • Humans
  • Inhibitory Concentration 50
  • Liver / enzymology
  • Male
  • Microsomes, Liver / drug effects*
  • Microsomes, Liver / enzymology*
  • Molecular Structure
  • Rats
  • Rats, Wistar


  • Cytochrome P-450 CYP1A2 Inhibitors
  • Cytochrome P-450 CYP2E1 Inhibitors
  • Cytochrome P-450 CYP3A Inhibitors
  • Cytochrome P-450 CYP2E1
  • Aryl Hydrocarbon Hydroxylases
  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19
  • chlorzoxazone 6-hydroxylase, rat
  • Capsaicin
  • dihydrocapsaicin