In vitro and in vivo inhibition of pulmonary cytochrome P450 activities by piperine, a major ingredient of piper species

Indian J Exp Biol. 1991 Jun;29(6):568-73.


In vitro and in vivo modulation of drug metabolizing enzymes by piperine was investigated in microsomes of rats and guinea pigs. In vitro piperine caused concentration related inhibition (50% at 100 microM) of arylhydrocarbon hydroxylase (AHH) and 7-ethoxycourmarin deethylase (7ECDE) activities, which were comparable in control and 3-methylcholanthrene (3MC) treated rats. In guinea pig microsomes however, piperine caused strong inhibition at lower concentrations (35% at 10 microM) and relatively much lesser inhibition with further increase in piperine concentrations. A Dixon plot of the kinetic data of both AHH and 7ECDE indicated noncompetitive inhibition with a Ki of approx. 100 microM. In vivo, piperine given at a dose of 25 mg/kg body wt to rats caused a maximal inhibition at 1 hr of both the enzymes, while only AHH returned to normal value within 4 hr. Similarly, upon daily treatment of piperine (15 mg/kg body wt) to rats for 7 days, 7ECDE was consistently inhibited, while AHH showed faster recovery. Piperine thus appeared to cause differential inhibition of two forms of cytochrome P450 and thus would accordingly affect the steady-state level of those drugs metabolized by these pulmonary forms of cytochromes P450.

MeSH terms

  • Alkaloids*
  • Animals
  • Benzodioxoles
  • Cytochrome P-450 Enzyme Inhibitors*
  • Guinea Pigs
  • Lung / drug effects
  • Lung / enzymology*
  • Male
  • Piperidines / pharmacology*
  • Polyunsaturated Alkamides
  • Rats


  • Alkaloids
  • Benzodioxoles
  • Cytochrome P-450 Enzyme Inhibitors
  • Piperidines
  • Polyunsaturated Alkamides
  • piperine