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
Coordinación de Tecnología de Alimentos de Origen Animal, Centro de Investigación en Alimentación y Desarrollo, A.C. Carretera Gustavo Enrique Astiazarán Rosas No. 46, La Victoria, Hermosillo 83304, Mexico.
Laboratorio de Toxicología Genética, Instituto Nacional de Pediatría, Insurgentes Sur 3700-C, Insurgentes Cuicuilco, Coyoacán, Ciudad de México 04530, Mexico.
Plants (Basel). 2023 Jun 17;12(12):2354. doi: 10.3390/plants12122354.
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 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 -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) for unheated ASE was 353.6 µg/mL and 75.9 µg/mL for heated ASE in EROD assay. An IC value of 288.4 ± 5.8 µg/mL was calculated for non-heated ASE in MROD assay. However, after heat treatment, the IC value was 232.1 ± 7.4 µg/mL. Molecular docking of corotoxigenin-3--glucopyranoside, one of the main components of ASE, with CYP1A1/2 structure, was performed. Results show that the interaction of corotoxigenin-3--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.
植物提取物先前已证明对熟肉中常见的杂环芳香胺（HAA）具有抗增殖活性和抗诱变活性。本研究的目的是评估药用植物提取物（ASE）的乙醇提取物在未加热和加热（180℃）条件下体外抑制CYP1A1和CYP1A2活性的能力，这两种酶在很大程度上负责HAA的生物活化。在暴露于ASE（0.002 - 960μg/mL）的大鼠肝微粒体中进行乙氧基试卤灵和甲氧基试卤灵脱烷基化试验。ASE以剂量依赖性方式发挥抑制作用。在EROD试验中，未加热的ASE的半抑制浓度（IC）为353.6μg/mL，加热的ASE为75.9μg/mL。在MROD试验中，未加热的ASE的IC值计算为288.4±5.8μg/mL。然而，热处理后，IC值为232.1±7.4μg/mL。对ASE的主要成分之一毒毛旋花子苷元-3-β-葡萄糖苷与CYP1A1/2结构进行了分子对接。结果表明，毒毛旋花子苷元-3-β-葡萄糖苷与CYP1A1/2的α-螺旋相互作用，而α-螺旋与活性位点和血红素辅因子相关，这可能解释了植物提取物的抑制特性。结果表明，ASE抑制CYP1A酶亚家族，并可能通过抑制促诱变膳食HAA的生物活化而潜在地作为一种化学预防剂。
