Euterpe oleracea Mart. (açaí) is a widely consumed botanical supplement marketed for antioxidant, anti-inflammatory, and antiproliferative properties. Despite its popularity, limited data exist on its ability to modulate drug-metabolizing enzymes and transporters-critical determinants of pharmacokinetic botanical-drug interactions. This study evaluated the cytotoxicity and induction potential of açaí extracts on cytochrome P450 (CYP450) enzymes and drug transporters using physiologically relevant in vitro models. Test samples included aqueous, acidic methanol, methanol, and ethanol extracts of açaí berry powder (Mountain Rose) and commercial capsules (Nature's Way, Natrol), selected to reflect consumer products and enhance translational relevance. Cytotoxicity was assessed using CellTiter-Glo® luminescent assay in sandwich-cultured human hepatocytes. Induction of CYP1A2, CYP2B6, CYP3A4, P-glycoprotein (P-gp), and organic anion transporting polypeptides (OATP1B1/B3) was evaluated at the mRNA level via RT-qPCR in the same hepatocyte model. Functional transporter activity was assessed using intracellular probe accumulation assays in LS174T human colon carcinoma cells, a complementary model for preliminary screening. A time- and dose-dependent reduction in hepatocyte viability occurred with specific extracts, notably MRAC (acidic methanol), MRME (methanol), MRET (ethanol), and F4AC (acidic methanol, Natrol). However, none significantly induced CYP450 or transporter expression. Preliminary functional assays also showed minimal impact on P-gp and OATP activity. While preliminary, this study provides a comprehensive evaluation of açaí-mediated modulation of key pharmacokinetic pathways and underscores the need for rigorous assessment of botanical extracts to better predict potential botanical-drug interactions.
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