Cargando…

Inhibition of the CYP Enzymatic System Responsible of Heterocyclic Amines Bioactivation by an Asclepias subulata Extract

Asclepias subulata plant extract has previously demonstrated antiproliferative activity and antimutagenicity against heterocyclic aromatic amines (HAAs) commonly found in cooked meat. The objective of this work was to evaluate the in vitro ability of an ethanolic extract from the medicinal plant Asc...

Descripción completa

Detalles Bibliográficos
Autores principales: Gutiérrez-Pacheco, Samaria Lisdeth, Peña-Ramos, Etna Aida, Santes-Palacios, Rebeca, Valenzuela-Melendres, Martin, Hernández-Mendoza, Adrián, Burgos-Hernández, Armando, Robles-Zepeda, Ramón Enrique, Espinosa-Aguirre, Jesús Javier
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10305697/
https://www.ncbi.nlm.nih.gov/pubmed/37375979
http://dx.doi.org/10.3390/plants12122354
_version_ 1785065794919464960
author Gutiérrez-Pacheco, Samaria Lisdeth
Peña-Ramos, Etna Aida
Santes-Palacios, Rebeca
Valenzuela-Melendres, Martin
Hernández-Mendoza, Adrián
Burgos-Hernández, Armando
Robles-Zepeda, Ramón Enrique
Espinosa-Aguirre, Jesús Javier
author_facet Gutiérrez-Pacheco, Samaria Lisdeth
Peña-Ramos, Etna Aida
Santes-Palacios, Rebeca
Valenzuela-Melendres, Martin
Hernández-Mendoza, Adrián
Burgos-Hernández, Armando
Robles-Zepeda, Ramón Enrique
Espinosa-Aguirre, Jesús Javier
author_sort Gutiérrez-Pacheco, Samaria Lisdeth
collection PubMed
description Asclepias subulata plant extract has previously demonstrated antiproliferative activity and antimutagenicity against heterocyclic aromatic amines (HAAs) commonly found in cooked meat. The objective of this work was to evaluate the in vitro ability of an ethanolic extract from the medicinal plant Asclepias subulata extract (ASE), non-heated and heated (180 °C), to inhibit the activity of CYP1A1 and CYP1A2, which are largely responsible for HAAs bioactivation. Ethoxyresorufin and methoxyresorufin O-dealkylation assays were performed in rat liver microsomes exposed to ASE (0.002–960 µg/mL). ASE exerted an inhibitory effect in a dose-dependent manner. The half inhibitory concentration (IC(50)) for unheated ASE was 353.6 µg/mL and 75.9 µg/mL for heated ASE in EROD assay. An IC(40) value of 288.4 ± 5.8 µg/mL was calculated for non-heated ASE in MROD assay. However, after heat treatment, the IC(50) value was 232.1 ± 7.4 µg/mL. Molecular docking of corotoxigenin-3-O-glucopyranoside, one of the main components of ASE, with CYP1A1/2 structure, was performed. Results show that the interaction of corotoxigenin-3-O-glucopyranoside with CYP1A1/2s’ α-helices, which are related with the active site and the heme cofactor, may explain the plant extract’s inhibitory properties. Results showed that ASE inhibits CYP1A enzymatic subfamily and may potentially act as a chemopreventive agent by inhibiting bioactivation of promutagenic dietary HAAs.
format Online
Article
Text
id pubmed-10305697
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-103056972023-06-29 Inhibition of the CYP Enzymatic System Responsible of Heterocyclic Amines Bioactivation by an Asclepias subulata Extract Gutiérrez-Pacheco, Samaria Lisdeth Peña-Ramos, Etna Aida Santes-Palacios, Rebeca Valenzuela-Melendres, Martin Hernández-Mendoza, Adrián Burgos-Hernández, Armando Robles-Zepeda, Ramón Enrique Espinosa-Aguirre, Jesús Javier Plants (Basel) Article Asclepias subulata plant extract has previously demonstrated antiproliferative activity and antimutagenicity against heterocyclic aromatic amines (HAAs) commonly found in cooked meat. The objective of this work was to evaluate the in vitro ability of an ethanolic extract from the medicinal plant Asclepias subulata extract (ASE), non-heated and heated (180 °C), to inhibit the activity of CYP1A1 and CYP1A2, which are largely responsible for HAAs bioactivation. Ethoxyresorufin and methoxyresorufin O-dealkylation assays were performed in rat liver microsomes exposed to ASE (0.002–960 µg/mL). ASE exerted an inhibitory effect in a dose-dependent manner. The half inhibitory concentration (IC(50)) for unheated ASE was 353.6 µg/mL and 75.9 µg/mL for heated ASE in EROD assay. An IC(40) value of 288.4 ± 5.8 µg/mL was calculated for non-heated ASE in MROD assay. However, after heat treatment, the IC(50) value was 232.1 ± 7.4 µg/mL. Molecular docking of corotoxigenin-3-O-glucopyranoside, one of the main components of ASE, with CYP1A1/2 structure, was performed. Results show that the interaction of corotoxigenin-3-O-glucopyranoside with CYP1A1/2s’ α-helices, which are related with the active site and the heme cofactor, may explain the plant extract’s inhibitory properties. Results showed that ASE inhibits CYP1A enzymatic subfamily and may potentially act as a chemopreventive agent by inhibiting bioactivation of promutagenic dietary HAAs. MDPI 2023-06-17 /pmc/articles/PMC10305697/ /pubmed/37375979 http://dx.doi.org/10.3390/plants12122354 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Gutiérrez-Pacheco, Samaria Lisdeth
Peña-Ramos, Etna Aida
Santes-Palacios, Rebeca
Valenzuela-Melendres, Martin
Hernández-Mendoza, Adrián
Burgos-Hernández, Armando
Robles-Zepeda, Ramón Enrique
Espinosa-Aguirre, Jesús Javier
Inhibition of the CYP Enzymatic System Responsible of Heterocyclic Amines Bioactivation by an Asclepias subulata Extract
title Inhibition of the CYP Enzymatic System Responsible of Heterocyclic Amines Bioactivation by an Asclepias subulata Extract
title_full Inhibition of the CYP Enzymatic System Responsible of Heterocyclic Amines Bioactivation by an Asclepias subulata Extract
title_fullStr Inhibition of the CYP Enzymatic System Responsible of Heterocyclic Amines Bioactivation by an Asclepias subulata Extract
title_full_unstemmed Inhibition of the CYP Enzymatic System Responsible of Heterocyclic Amines Bioactivation by an Asclepias subulata Extract
title_short Inhibition of the CYP Enzymatic System Responsible of Heterocyclic Amines Bioactivation by an Asclepias subulata Extract
title_sort inhibition of the cyp enzymatic system responsible of heterocyclic amines bioactivation by an asclepias subulata extract
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10305697/
https://www.ncbi.nlm.nih.gov/pubmed/37375979
http://dx.doi.org/10.3390/plants12122354
work_keys_str_mv AT gutierrezpachecosamarialisdeth inhibitionofthecypenzymaticsystemresponsibleofheterocyclicaminesbioactivationbyanasclepiassubulataextract
AT penaramosetnaaida inhibitionofthecypenzymaticsystemresponsibleofheterocyclicaminesbioactivationbyanasclepiassubulataextract
AT santespalaciosrebeca inhibitionofthecypenzymaticsystemresponsibleofheterocyclicaminesbioactivationbyanasclepiassubulataextract
AT valenzuelamelendresmartin inhibitionofthecypenzymaticsystemresponsibleofheterocyclicaminesbioactivationbyanasclepiassubulataextract
AT hernandezmendozaadrian inhibitionofthecypenzymaticsystemresponsibleofheterocyclicaminesbioactivationbyanasclepiassubulataextract
AT burgoshernandezarmando inhibitionofthecypenzymaticsystemresponsibleofheterocyclicaminesbioactivationbyanasclepiassubulataextract
AT robleszepedaramonenrique inhibitionofthecypenzymaticsystemresponsibleofheterocyclicaminesbioactivationbyanasclepiassubulataextract
AT espinosaaguirrejesusjavier inhibitionofthecypenzymaticsystemresponsibleofheterocyclicaminesbioactivationbyanasclepiassubulataextract