CYP3A4 and CYP2D6 inhibitory activities of Indonesian medicinal plants

• Published in: Phytomedicine (Stuttgart) 2006-01, Vol.13 (1), p.67-73
• Main Authors: Usia, T., Iwata, H., Hiratsuka, A., Watabe, T., Kadota, S., Tezuka, Y.
• Format: Article
• Language: English
• Subjects: CYP2D6; CYP3A4; Cytochrome P-450; Cytochrome P-450 CYP2D6 - chemistry; Cytochrome P-450 CYP2D6 - metabolism; Cytochrome P-450 CYP2D6 Inhibitors; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System - chemistry; Cytochrome P-450 Enzyme System - metabolism; Cytochrome P450; Drug interaction; Drugs; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; Health aspects; Indonesia; Inhibition; Jamu; Medicinal plants; Medicine, Traditional; Plant Extracts - chemistry; Plant Extracts - pharmacology; Plants, Medicinal - chemistry; Properties; Structure-activity relationship (Pharmacology); Structure-activity relationships
• ISSN: 0944-7113; 1618-095X
• DOI: 10.1016/j.phymed.2004.06.022

Thirty samples of Indonesian medicinal plants were analyzed for their capacity to inhibit in vitro metabolism by human cytochrome P450 3A4 (CYP3A4) and CYP2D6 with a radiometric assay. The MeOH-soluble fractions of 25 samples, prepared from water extracts, demonstrated inhibitory activity more than 50% on the metabolism mediated by CYP3A4, and 21 samples on the metabolism mediated by CYP2D6. Among the MeOH-soluble fractions, Piper nigrum leaf showed the highest inhibitory activity against CYP3A4 (91.7%), and Punica granatum against CYP2D6 (98.1%). The water extracts of which MeOH-soluble fraction showed inhibitory activity more than 70% were fractionated with EtOAc. From the EtOAc-soluble fractions, Curcuma heyneana (67.0%), Pi. cubeba (75.0%), Pi. nigrum fruit (84.0%), Pi. nigrum leaf (85.8%), and Zingiber aromaticum (75.3%) demonstrated inhibitory activity more than 50% on the metabolism mediated by CYP3A4, but only Pi. nigrum fruit (72.8%) and Pi. nigrum leaf (69.1%) showed strong inhibitory activity against CYP2D6. For samples that showed more than 70% inhibition, their IC 50 values were determined. The most potent inhibitory activity against CYP3A4 (IC 50 value of 25 μg/ml) was found for the extract of Pi. nigrum leaf, while that of Catharanthus roseus showed the most potent inhibitory effect against CYP2D6 (IC 50 value of 11 μg/ml). These results should indicate once more the possibility of potential medicinal plant–drug interactions.