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

Samaria Lisdeth Gutiérrez-Pacheco, Etna Aida Peña-Ramos, Rebeca Santes-Palacios, Martin Valenzuela-Melendres, Adrián Hernández-Mendoza, Armando Burgos-Hernández, Ramón Enrique Robles-Zepeda, Jesús Javier Espinosa-Aguirre*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

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 (IC50) for unheated ASE was 353.6 µg/mL and 75.9 µg/mL for heated ASE in EROD assay. An IC40 value of 288.4 ± 5.8 µg/mL was calculated for non-heated ASE in MROD assay. However, after heat treatment, the IC50 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.

Original languageEnglish
Article number2354
JournalPlants
Volume12
Issue number12
DOIs
StatePublished - Jun 2023

Bibliographical note

Publisher Copyright:
© 2023 by the authors.

Keywords

  • CYP inhibition
  • antimutagens
  • chemoprotection
  • heterocyclic amines
  • medicinal plant
  • xenobiotics

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