Molecules, Vol. 29, Pages 322: Hydroxylated Tetramethoxyflavone Affects Intestinal Cell Permeability and Inhibits Cytochrome P450 Enzymes

This study aims to provide insights into the chemical and biological properties of hydroxylated TMF and evaluates its effects on intestinal cell permeability and cytochrome P450 (CYP) inhibition. Liquid chromatography–mass spectrometry (LC-MS) and microsomes analyze the TMFs and hydroxylated TMFs, elucidating cell penetration and metabolic inhibition potential. 3H7-TMF shows the fastest (1-h) transport efficiency in intestinal cells. The Caco-2 cell model exhibits significant transport and absorption efficiency. Dissolved hydroxyl-TMF with hydrophilicity possibly permeates the gut. 3H7-TMF has higher transport efficiency (46%) 3H6-TMF (39%). IC50 values of TMFs (78-TMF, 57-TMF, 3H7-TMF, 3H6-TMF) against CYP enzymes (CYP1A2, CYP2D6, CYP2C9, CYP2C19, CYP3A4) range from 0.15 to 108 μM, indicating potent inhibition. Hydroxyl groups enhance TMF hydrophilicity and membrane permeability. TMFs display varied inhibitory effects due to hydroxyl and methoxy hindrance. This study underscores the strong CYP inhibitory capabilities in these TMFs, implying potential food–drug interactions if used in medicines or supplements. These findings can also help with food nutrition improvement and pharma food developments through innovative approaches for Citrus waste valorization.
Source: Molecules - Category: Chemistry Authors: Tags: Article Source Type: research