Background: Maytenus ilicifolia is a Brazilian popular medicine commonly used to treat ulcer and
gastritis. Despite the absence of toxicity regarding its consumption, possible interactions when co-administrated with
conventional drugs, are unknown.
Objective: This study aimed to evaluate the effects of M. ilicifolia extracts on Cytochrome P450 3A (CYP3A) and
P-glycoprotein (P-gp) activities.
Methods: The extracts were obtained by infusion (MI) or turbo-extraction using hydro-acetonic solvent (MT70). The
content of polyphenols in each extract was determined. To assess the modulation of M. ilicifolia on P-gp activity, the
uptake of fexofenadine (FEX) by Caco-2 cells was investigated in the absence or presence of MI or MT70. The effect
on CYP3A activity was evaluated by the co-administration of midazolam (MDZ) with each extract in male Wistar
rats. The pharmacokinetic parameters of the drug were determined and compared with those from the control group.
The content of total phenolic compounds, tannins, and flavonoids on MT70 extract was about double of that found in
Results: In the presence of the extracts, the uptake of the P-gp marker (FEX) by Caco-2 cells increased from
1.7 ± 0.4 ng.mg-1 protein (control) to 3.5 ± 0.2 ng.mg-1 protein (MI) and 4.4 ± 0.5 ng.mg-1 protein (MT70),
respectively. When orally co-administrated with MDZ (substrate of CYP3A), the extracts augmented the AUC(0-∞)
(Control: 911.7 ± 215.7 ng.h.mL-1; MI: 1947 ± 554.3 ng.h.mL-1; MT70: 2219.0 ± 506.3 ng.h.mL-1) and the
Cmax (Control: 407.7 ± 90.4 ng.mL-1; MI: 1770.5 ± 764.5 ng.mL-1; MT70: 1987.2 ± 544.9 ng.mL-1) of the drug in rats
indicating a 50% reduction of the oral Cl. No effect was observed when midazolam was given intravenously.
Conclusion: The results suggest that M. ilicifolia can inhibit the intestinal metabolism and transport of drugs
mediated by CYP3A and P-gp, respectively, however, the involvement of other transporters and the clinical
relevance of such interaction still need to be clarified.