Evaluation of the Effects of Maytenus ilicifolia on the Activities of Cytochrome P450 3A and P-glycoprotein.
ATP Binding Cassette Transporter, Subfamily B, Member 1
/ agonists
Animals
Caco-2 Cells
Cell Line
Cytochrome P-450 CYP3A
/ metabolism
Cytochrome P-450 CYP3A Inhibitors
/ pharmacology
Drug Interactions
Humans
Ketoconazole
/ pharmacology
Male
Maytenus
/ chemistry
Midazolam
/ pharmacokinetics
Plant Extracts
/ pharmacology
Quinolines
/ pharmacology
Rats
Rats, Wistar
Terfenadine
/ analogs & derivatives
Caco-2
Maytenus ilicifolia
P-glycoprotein
cytochrome P4503A
herbal-drug interaction
midazolam.
Journal
Current drug metabolism
ISSN: 1875-5453
Titre abrégé: Curr Drug Metab
Pays: Netherlands
ID NLM: 100960533
Informations de publication
Date de publication:
2020
2020
Historique:
received:
10
11
2019
revised:
16
02
2020
accepted:
16
03
2020
pubmed:
13
5
2020
medline:
11
5
2021
entrez:
13
5
2020
Statut:
ppublish
Résumé
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. This study aimed to evaluate the effects of M. ilicifolia extracts on Cytochrome P450 3A (CYP3A) and P-glycoprotein (P-gp) activities. 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 MI. 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. 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.
Sections du résumé
BACKGROUND
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
OBJECTIVE
This study aimed to evaluate the effects of M. ilicifolia extracts on Cytochrome P450 3A (CYP3A) and P-glycoprotein (P-gp) activities.
METHODS
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 MI.
RESULTS
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
CONCLUSIONS
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.
Identifiants
pubmed: 32394829
pii: CDM-EPUB-106564
doi: 10.2174/1389200221666200512112718
doi:
Substances chimiques
ATP Binding Cassette Transporter, Subfamily B, Member 1
0
Cytochrome P-450 CYP3A Inhibitors
0
Plant Extracts
0
Quinolines
0
Terfenadine
7BA5G9Y06Q
fexofenadine
E6582LOH6V
Cytochrome P-450 CYP3A
EC 1.14.14.1
tariquidar
J58862DTVD
Midazolam
R60L0SM5BC
Ketoconazole
R9400W927I
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
281-290Informations de copyright
Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.