Use of Physiologically Based Kinetic Modeling-Based Reverse Dosimetry to Predict In Vivo Nrf2 Activation by EGCG and Its Colonic Metabolites in Humans.
J Agric Food Chem
; 70(43): 14015-14031, 2022 Nov 02.
Article
en En
| MEDLINE
| ID: mdl-36262111
ABSTRACT
(-)-Epigallocatechin gallate (EGCG) is prone to microbial metabolism when reaching the colon. This study aimed to develop a human physiologically based kinetic (PBK) model for EGCG, with sub-models for its colonic metabolites gallic acid and pyrogallol. Results show that the developed PBK model could adequately predict in vivo time-dependent blood concentrations of EGCG after either the single or repeated oral administration of EGCG under both fasting and non-fasting conditions. The predicted in vivo blood Cmax of EGCG indicates that the Nrf2 activation is limited, while concentrations of its metabolites in the intestinal tract may reach levels that are higher than that of EGCG and also high enough to activate Nrf2 gene transcription. Taken together, combining in vitro data with a human PBK model allowed the prediction of a dose-response curve for EGCG-induced Nrf2-mediated gene expression in humans and provided insights into the contribution of gut microbial metabolites to this effect.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Catequina
/
Factor 2 Relacionado con NF-E2
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
J Agric Food Chem
Año:
2022
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
EEUU
/
ESTADOS UNIDOS
/
ESTADOS UNIDOS DA AMERICA
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EUA
/
UNITED STATES
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UNITED STATES OF AMERICA
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US
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USA