St John's wort modulation and developmental expression of multidrug transporters in the rat

Extracts of St John's wort (SJW) (Hypericum perforatum) are a potent inducer of enzymes of the cytochrome P450 system and of the transport protein P-glycoprotein, and interactions with a range of commonly prescribed medications have been described. In addition, recent experimental data suggest that, this otherwise safe treatment, could have some side effects when consumed during pregnancy and lactation. The aim of this study was to investigate, in Wistar rats, the effect of a treatment with high doses of SJW extract (100 and 1000 mg/kg/day) administered prenatally and during breastfeeding, on the level of transcripts of mdr1a, mdr1b, mrp1, mrp2 and cyp3A2 genes. All transcripts were detected in the liver, and their level of expression increased from fetuses to adults. SJW administration, at both dosages, caused a significant decrease of the levels of mdr1a, mdr1b, mrp1 and mrp2 in the livers of fetuses, and an increase in the levels of mdr1a, mdr1b, mrp2 and cyp3A2 in the mothers. In the other organs examined, a physiological regulation during ontogenesis was also evident, but SJW administration did not modify the expression level of the considered transcripts. These data suggest that the administration of the extract together with drugs that are substrates of transport proteins could be particularly hazardous during pregnancy.