Extracts and kavalactones of Piper methysticum G. Forst (kava-kava) inhibit P-glycoprotein in vitro

Drug Metab Dispos. 2005 Nov;33(11):1580-3. doi: 10.1124/dmd.105.005892. Epub 2005 Jul 28.


Root extracts from kava-kava (Piper methysticum G. Forst) are clinically used for the treatment of anxiety and restlessness. Due to reported cases of liver toxicity, kava-kava extracts were withdrawn from the market in several countries in 2002. Because the efflux transporter P-glycoprotein (P-gp) is involved in the absorption, distribution, and excretion of many drugs and often participates in drug-drug interactions, we studied the effect of a crude kava extract and the main kavalactones kavain, dihydrokavain, methysticin, dihydromethysticin, yangonin, and desmethoxyyangonin on the P-gp-mediated efflux of calcein-acetoxymethylester in the P-gp-overexpressing cell line P388/dx and the corresponding cell line P388. The crude extract and the kavalactones showed a moderate to potent inhibitory activity with f2) (concentration needed to double baseline fluorescence) values of 170 microg/ml and 17 to 90 microM, respectively. The f2 value of yangonin could not be determined due to its higher lipophilicity. In conclusion, our results for the first time demonstrate P-gp-inhibitory activity of kava-kava and its components in vitro.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / antagonists & inhibitors*
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • Animals
  • Anti-Anxiety Agents / isolation & purification
  • Anti-Anxiety Agents / pharmacology*
  • Cell Line, Tumor
  • Dose-Response Relationship, Drug
  • Fluoresceins
  • Kava*
  • Lactones / isolation & purification
  • Lactones / pharmacology*
  • Leukemia P388
  • Mice
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • Plant Roots
  • Pyrones / isolation & purification
  • Pyrones / pharmacology
  • Transfection


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Anti-Anxiety Agents
  • Fluoresceins
  • Lactones
  • Plant Extracts
  • Pyrones
  • desmethoxyyangonin
  • calcein AM
  • dihydrokavain
  • kavain