Piperine-mediated inhibition of glucuronidation activity in isolated epithelial cells of the guinea-pig small intestine: evidence that piperine lowers the endogeneous UDP-glucuronic acid content

J Pharmacol Exp Ther. 1986 Feb;236(2):488-93.


Piperine (1-peperoyl piperidine), a major component of the Piper species was reported recently by us to inhibit the activities of rat hepatic monooxygenases and UDP-glucuronyltransferase. This study explores further the basis of inhibition of glucuronidation. The effect of piperine on the rate of glucuronidation of 3-hydroxybenzo(a) pyrene and UDP-glucuronic acid content in the intact isolated epithelial cells of the guinea-pig small intestine was studied. The cells offered a fairly good system to study the modulation of glucuronidation activity. Glucuronidation of 3-hydroxybenzo(a) pyrene was dependent on the time of incubation, cellular protein and substrate concentration. From the kinetics of glucuronidation of 3-hydroxybenzo(a)pyrene in the isolated cell preparation the Vmax of 0.5 nmol of BP-3-glucuronide formed per min/mg of protein and Km of 25 microM were observed. The endogeneous concentration of UDP-glucuronic acid observed was 1.6 to 2.3 nmol/mg of cellular protein. Piperine caused a concentration-related decrease in UDP-glucuronic acid content and the rate of glucuronidation in the cells. It required much lower concentrations of piperine than D-galactosamine to diminish the endogeneous level of UDP-glucuronic acid. Rate of glucuronidation of 3-hydroxybenzo (a) pyrene was dependent on the endogeneous level of UDP-glucuronic acid. At 50 microM piperine, the rate of glucuronidation was reduced to about 50% of the basal rate. Piperine caused noncompetitive inhibition of hepatic microsomal UDP-glucuronyltransferase with Ki of 70 microM. The studies demonstrate that piperine modifies the rate of glucuronidation by lowering the endogeneous UDP-glucuronic acid content and also by inhibiting the transferase activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids*
  • Animals
  • Benzodioxoles
  • Benzopyrenes / metabolism
  • Cell Survival / drug effects
  • Epithelium / metabolism
  • Galactosamine / pharmacology
  • Glucuronates / metabolism*
  • Glucuronosyltransferase / antagonists & inhibitors
  • Guinea Pigs
  • In Vitro Techniques
  • Intestine, Small / metabolism*
  • Kinetics
  • Male
  • Piperidines / pharmacology*
  • Polyunsaturated Alkamides
  • Uridine Diphosphate Glucuronic Acid / analysis*
  • Uridine Diphosphate Glucuronic Acid / metabolism
  • Uridine Diphosphate Sugars / analysis*


  • Alkaloids
  • Benzodioxoles
  • Benzopyrenes
  • Glucuronates
  • Piperidines
  • Polyunsaturated Alkamides
  • Uridine Diphosphate Sugars
  • Uridine Diphosphate Glucuronic Acid
  • 3-hydroxybenzo(a)pyrene
  • Galactosamine
  • Glucuronosyltransferase
  • piperine