The use of medicinal plants concomitantly with conventional drugs can result in 
herb-drug interactions that cause fluctuations in drug bioavailability and 
consequent therapeutic failure and/or toxic effects. The CYP superfamily of 
enzymes plays an important role in herb-drug interactions. Among CYP enzymes, 
CYP3A4 and CYP2D6 are the most relevant since they metabolize about 50% and 30% 
of the drugs on the market, respectively. Thus, the main goal of this study was 
to evaluate the occurrence of in vitro interactions between medicinal plant 
extracts and drug substrates of CYP3A4 and CYP2D6 enzymes. Standardized extracts 
from nine medicinal plants (Bauhinia forficata, Cecropia glaziovii, Cimicifuga 
racemosa, Cynara scolymus, Echinacea sp., Ginkgo biloba, Glycine max, Ilex 
paraguariensis, and Matricaria recutita) were evaluated for their potential 
interactions mediated by CYP3A4 and CYP2D6 enzymes. Among the extracts tested, 
C. glaziovii (red embaúba) showed the most relevant inhibitory effects of CYP3A4 
and CYP2D6 activity, while I. paraguariensis (yerba mate) inhibited CYP3A4 
activity. Both extracts were chemically analyzed by UPLC-MS/MS, and these 
inhibitory effects could lead to clinically potential and relevant interactions 
with the drug substrates of these isoenzymes.