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autoimmune diseases. Phytochemical compounds in soy (Glycine max) foods, such as isoflavones, have been reported for their anti-inflammatory properties. Aim: the anti-inflammatory activity of DZ (daidzein) and EQ (equol) were investigated in an ex vivo model of LPS-stimulated murine peritoneal macrophages and by molecular docking correlation. Methods: Cells were pre-treated with DZ (25, 50, and 100 \u00b5M) or EQ (5, 10, and 25 \u00b5M), followed by LPS stimulation. The levels of PGE2, NO, TNF-\u03b1, IL-6, and IL-1\u03b2 were analyzed by ELISA, whereas the expressions of COX-2, iNOS, NLRP3, ASC, caspase 1, and IL-18 were measured by Western blotting. Also, the potential for transcriptional modulation by targeting NF-\u03baB, COX-2, iNOS, NLRP3, ASC, and caspase 1 was investigated by molecular docking. Results: The anti-inflammatory responses observed may be due to the modulation of NF-\u03baB due to the binding of DZ or EQ, which is translated into decreased TNF-\u03b1, COX-2, iNOS, NLRP3, and ASC levels. Conclusion: This study establishes that DZ and EQ inhibit LPS-induced inflammatory responses in peritoneal murine macrophages via down-regulation of NO and PGE2 generation, as well as the inhibition of the canonical inflammasome pathway, regulating NLRP3, and consequently decreasing IL-1\u03b2 and IL-18 activation.<\/jats:p>","DOI":"10.3390\/ph17050647","type":"journal-article","created":{"date-parts":[[2024,5,16]],"date-time":"2024-05-16T11:26:17Z","timestamp":1715858777000},"page":"647","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Daidzein and Equol: Ex Vivo and In Silico Approaches Targeting COX-2, iNOS, and the Canonical Inflammasome Signaling Pathway"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0132-3149","authenticated-orcid":false,"given":"Yazm\u00edn K.","family":"M\u00e1rquez-Flores","sequence":"first","affiliation":[{"name":"Departamento de Farmacia, Escuela Nacional de Ciencias Biol\u00f3gicas, Campus Zacatenco, Instituto Polit\u00e9cnico Nacional, Av. Wilfrido Massieu s\/n Col. Zacatenco, Mexico City C.P. 07738, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizdath","family":"Mart\u00ednez-Galero","sequence":"additional","affiliation":[{"name":"Departamento de Farmacia, Escuela Nacional de Ciencias Biol\u00f3gicas, Campus Zacatenco, Instituto Polit\u00e9cnico Nacional, Av. Wilfrido Massieu s\/n Col. Zacatenco, Mexico City C.P. 07738, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9","family":"Correa-Basurto","sequence":"additional","affiliation":[{"name":"Laboratorio de Dise\u00f1o y Desarrollo de Nuevos F\u00e1rmacos y Productos Biotecnol\u00f3gicos, Escuela Superior de Medicina, Instituto Polit\u00e9cnico Nacional, Plan de San Luis y D\u00edaz Mir\u00f3n s\/n, Col. Santo Tomas, Mexico City C.P. 11340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8903-3834","authenticated-orcid":false,"given":"Yudibeth","family":"Sixto-L\u00f3pez","sequence":"additional","affiliation":[{"name":"Laboratorio de Dise\u00f1o y Desarrollo de Nuevos F\u00e1rmacos y Productos Biotecnol\u00f3gicos, Escuela Superior de Medicina, Instituto Polit\u00e9cnico Nacional, Plan de San Luis y D\u00edaz Mir\u00f3n s\/n, Col. Santo Tomas, Mexico City C.P. 11340, Mexico"},{"name":"Departamento de Qu\u00edmica Farmac\u00e9utica y Org\u00e1nica, Facultad de Farmacia, Campus de Cartuja, Universidad de Granada, 18071 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9111-6740","authenticated-orcid":false,"given":"Isabel","family":"Villegas","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy, University of Seville, Professor Garc\u00eda Gonz\u00e1lez Street 2, 41012 Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda \u00c1.","family":"Rosillo","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy, University of Seville, Professor Garc\u00eda Gonz\u00e1lez Street 2, 41012 Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"C\u00e1rdeno","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy, University of Seville, Professor Garc\u00eda Gonz\u00e1lez Street 2, 41012 Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6625-3818","authenticated-orcid":false,"given":"Catalina","family":"Alarc\u00f3n-de-la-Lastra","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy, University of Seville, Professor Garc\u00eda Gonz\u00e1lez Street 2, 41012 Seville, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1038\/s41421-020-0167-x","article-title":"Inflammasome Activation and Regulation: Toward a Better Understanding of Complex Mechanisms","volume":"6","author":"Zheng","year":"2020","journal-title":"Cell Discov."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1097\/MOG.0b013e32836157a4","article-title":"Inflammasomes in Inflammatory Bowel Disease Pathogenesis","volume":"29","author":"Hao","year":"2013","journal-title":"Curr. 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