RESUMO
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 microg/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 microg/ml). These results should indicate once more the possibility of potential medicinal plant-drug interactions.
Assuntos
Inibidores do Citocromo P-450 CYP2D6 , Inibidores das Enzimas do Citocromo P-450 , Inibidores Enzimáticos/farmacologia , Extratos Vegetais/farmacologia , Plantas Medicinais/química , Citocromo P-450 CYP2D6/química , Citocromo P-450 CYP2D6/metabolismo , Citocromo P-450 CYP3A , Sistema Enzimático do Citocromo P-450/química , Sistema Enzimático do Citocromo P-450/metabolismo , Inibidores Enzimáticos/química , Indonésia , Medicina Tradicional , Extratos Vegetais/químicaRESUMO
A protective effect of the SOD (superoxide dismutase)-DIVEMA (divinyl ether and maleic anhydride) conjugate on I-R (ischemia-reperfusion) liver injury was demonstrated. Twenty minutes of normothermic hepatic ischemia was induced by clamping the portal triad of Sprague-Dawley rats. Five minutes before the end of ischemia, SOD, SOD-DIVEMA, or NaCl (0.9%) was given intravenously. Using intravital fluorescence microscopy, hepatic microvascular perfusion was analyzed before ischemia and repeatedly during the 120-min reperfusion period. SOD-DIVEMA significantly restored the sinusoidal perfusion rate (control, 98.0 +/- 0.5; NaCl, 65.5 +/- 7. 7; SOD, 81.5 +/- 8.2; SOD-DIVEMA, 95.8 +/- 0.7%) and reduced the number of leukocytes stagnant in acini (control, 4.4 +/- 0.9; NaCl, 36.6 +/- 6.3; SOD, 27.7 +/- 6.8; SOD-DIVEMA, 12.3 +/- 3.3 cells/lobule) and adherent in postsinusoidal venules (control, 55.0 +/- 24; NaCl, 417 +/- 63; SOD, 253 +/- 58; SOD-DIVEMA, 40.0 +/- 14 cells/mm2). In addition, SOD-DIVEMA maintained postischemic hepatocellular integrity. The SOD-DIVEMA-treated group revealed higher serum SOD enzyme activity compared to the SOD group after 120 min of reperfusion (SOD-DIVEMA, 33.0 +/- 5.9; SOD, 8.6 +/- 3.1 U/ml). The beneficial effect of SOD-DIVEMA was most prominent after 120 min of reperfusion, indicating a longer intravascular half-life of SOD-DIVEMA.
