Abstract
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 Due to reported cases of liver toxicity, kava-kava extracts were withdrawn from the market in several countries in 2002.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 μg/ml and 17 to 90 μM, 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.
Footnotes
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This work was supported by Grant 01EC9902 from the German Ministry for Education and Research (Bundesministerium für Bildung und Forschung).
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Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.
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doi:10.1124/dmd.105.005892.
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ABBREVIATIONS: P450, cytochrome P450; P-gp, P-glycoprotein; calcein-AM, calcein-acetoxymethylester; DMSO, dimethyl sulfoxide; f2, concentration needed to double baseline fluorescence.
- Received June 1, 2005.
- Accepted July 27, 2005.
- The American Society for Pharmacology and Experimental Therapeutics
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