Evaluation of the Pharmacokinetic Interactions of Maytenus ilicifolia Mart. ex Reiss Extracts on Drug Intestinal Permeability and Hepatic Metabolism
Year: 2025
Type: article
Abstract: High Resolution Image Download MS PowerPoint Slide Maytenus ilicifolia Mart. ex Reiss is a plant native to South America, popularly used in the treatment of gastric disorders. The increase in the consumption of herbal products associated with conventional medications demands attention for the potential risks of interactions. The aim of the study was to evaluate potential pharmacokinetic interactions due to coadministration of M. ilicifolia extracts with drug substrates of P-glycoprotein (P-gp) and cytochrome P450 3A4 isoform (CYP3A4). Five extracts of M. ilicifolia were prepared, and the contents of the main secondary metabolites were determined. A high-performance liquid chromatography (HPLC) method was developed for the simultaneous quantitation of midazolam, nifedipine, and their respective metabolites and applied to assess the potential of M. ilicifolia extracts on hepatic metabolism mediated by the CYP3A4 enzyme. The influence of the extracts on the intestinal permeability of fexofenadine was evaluated by determining P-gp activity, using a Caco-2 cell model. The extracts were characterized in terms of total phenolic (1.77–11.46%), tannin (1.67–3.36%), and flavonoid (0.21–2.64%). The hydroacetonic extract (HAE1) exhibited a remaining activity (%RA) of 50.1% for the 1-hydroxylation of midazolam and 40.1% for the oxidation of nifedipine, indicating moderate inhibition of CYP3A4. HAE1 reduced the fexofenadine efflux ratio to an extent similar to that of verapamil (IC 50 = 20.42 μg/mL), suggesting an inhibitory effect on the P-gp activity. The extracts demonstrated the potential to inhibit both CYP3A4 and P-gp. Therefore, coadministration of M. ilicifolia -based preparations may potentially alter the pharmacokinetics of drugs that are substrates of these systems.
Source: ACS Omega
Authors: Sara Batista do Nascimento, Pedro Henrique Gomes dos Santos, Gustavo Henrique Oliveira Costa, Ícaro Salgado Perovani, Anderson Rodrigo Moraes de Oliveira, José Eduardo Gonçalves, Whocely Victor de Castro, Isabela da Costa César
Language: English
Subfield: Plant Science
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $1,935
Funders: Fundação de Amparo à Pesquisa do Estado de São Paulo, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Conselho Nacional de Desenvolvimento Científico e Tecnológico, Fundação de Amparo à Pesquisa do Estado de Minas Gerais, Universidade Federal de Minas Gerais, Pró-Reitoria de Pesquisa, Universidade Federal de Minas Gerais
Awards: Development of chromatographic / electrophoretic methods to be further applied in in vitro enzymatic inhibition studies and prediction of drug interactions of chiral pesticides - Phase 2, In vitro enantioselective evaluation of the effect of chiral pesticides on main human cytochrome P450 enzymes involved in drug metabolism: in vitro-in vivo correlation and prediction of pesticide-drug interaction, G1467195438, G2907441556, G3690646728, ENANTIOSSELETIVIDADE DE FITOFÁRMACOS EM PRODUTOS NATURAIS: AVALIAÇÃO DO PERFIL FARMACOCINÉTICO E BIODISTRIBUIÇÃO DE KAVAÍNA EM EXTRATOS DE KAVA-KAVA, G753403906, G8425984410
OpenAlex ID: W4414517848