Effect of chrysin and natural coumarins on UGT1A1 and 1A6 activities in rat and human hepatocytes in primary culture

Planta Med. 2007 Jul;73(8):742-7. doi: 10.1055/s-2007-981548. Epub 2007 Jun 28.


Flavonoids and coumarins are naturally occurring compounds that are widely distributed in vegetables and have a broad pharmacological activity. Inducibility of UDP-glucuronosyltransferases (UGTs) by xenobiotics is well documented and can be considered beneficial for health. In particular, UGT1A1-dependent bilirubin conjugation plays a critical role in the detoxification of neurotoxic bilirubin and phenobarbital-mediated UGT1A1 induction therapy is commonly used in the treatment of unconjugated hyperbilirubinemic diseases such as Crigler-Najjar type II disease. In the present study, the effects of the flavone chrysin and six natural coumarins isolated from various Rutaceous plants on UGT1A6-dependent P-nitrophenol and/or UGT1A1-dependent bilirubin glucuronoconjugation activities were evaluated in cultured rat and human hepatocytes and compared to those of the prototypical UGT1A inducers beta-naphthoflavone, phenobarbital and clofibric acid. After 3 days of treatment at a concentration of 25 microM, the pyranocoumarins avicennin and CIS-avicennol, and the furocoumarins bergapten and imperatorin, increased by 2-fold UGT1A1-dependent activity, equivalent to the increases obtained with chrysin at 25 microM, whereas in the presence of the simple coumarins such as coumarin or umbelliferone, UGT1A1-dependent activity was not modified. In terms of structural requirements for UGT1A1 induction, the present study suggests that the B-ring (phenyl) for chrysin and the furan or pyran rings for coumarins are essential for the biological activity.

MeSH terms

  • Animals
  • Coumarins / administration & dosage
  • Coumarins / pharmacology*
  • Coumarins / therapeutic use
  • Flavonoids / administration & dosage
  • Flavonoids / pharmacology*
  • Flavonoids / therapeutic use
  • Glucuronosyltransferase / metabolism*
  • Hepatocytes / drug effects*
  • Hepatocytes / metabolism
  • Humans
  • Microsomes, Liver / metabolism
  • Phytotherapy*
  • Rats
  • Rutaceae*


  • Coumarins
  • Flavonoids
  • chrysin
  • UDP-glucuronosyltransferase, UGT1A6
  • UGT1A1 enzyme
  • Glucuronosyltransferase