title: In vitro and in vivo inhibition of pulmonary cytochrome P450 activities by piperine, a major ingredient of piper species.
abstract: 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.
authors.affiliation: Biochemistry Section, Regional Research Laboratory, Jammu-Tawi, India.
authors.forename: R K
authors.initials: RK
authors.lastname: Reen
authors.forename: J
authors.initials: J
authors.lastname: Singh
mesh_terms: D000470:Alkaloids; D000818:Animals; D052117:Benzodioxoles; D065607:Cytochrome P-450 Enzyme Inhibitors; D006168:Guinea Pigs; D008168:Lung / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D010880:Piperidines / Q000494:pharmacology*; D053284:Polyunsaturated Alkamides; D051381:Rats
chemical_list: D000470:Alkaloids; D052117:Benzodioxoles; D065607:Cytochrome P-450 Enzyme Inhibitors; D010880:Piperidines; D053284:Polyunsaturated Alkamides; C008922:piperine