effects of European and Latin-American medicinal plants in CYP3A4 gene expression, glutathione levels, and P-glycoprotein activity.

Many medicinal plants species from European -such as - as well as Latin American traditions -such as , and are shortlisted by the Brazilian National Health System for future clinical use. However, they lack many data on their action upon some key ADME targets. In this study, we assess non-toxic concentrations (up to100 μg/ml) of their infusions for ability to modulate CYP3A4 mRNA gene expression and intracellular glutathione levels in HepG2 cells, as well as P-glycoprotein (P-gp) activity in vincristine-resistant Caco-2 cells (Caco-2 VCR). We further investigated the activation of human pregnane X receptor (hPXR) in transiently co-transfected HeLa cells and the inhibition of Gamma-glutamyl transferase (GGT) in HepG2 cells. Our results demonstrate and can significantly increase CYP3A4 mRNA gene expression in HepG2 cells. Only shown to do so likely via hPXR activation. P-gp activity was affected by and . Total intracellular glutathione levels were significantly depleted by exposure to all extracts except and This was accompanied by a lower GGT activity in the case of and , whilst , and increased it. Surprisingly, aqueous extract drastically decreased GGT activity (-48%, < 0.01). In conclusion, this preclinical study shows that the administration of some of these herbal medicines causes disturbances to key drug metabolism mechanisms. We recommend active pharmacovigilance for (Mart.) L. P. Queiroz, Cooper, Raddi, and L. which were able to alter all targets in our preclinical study.