Article
Daidzein and Equol: Ex Vivo and In Silico Approaches Targeting COX-2, iNOS, and the Canonical Inflammasome Signaling Pathway
Author/s | Márquez Flores, Yazmín K.
Martínez Galero, Elizdath Correa Basurto, José Sixto López, Yudibeth Villegas Lama, Isabel Rosillo Ramírez, María de los Ángeles Cárdeno Galván, Ana Alarcón de la Lastra Romero, Catalina |
Department | Universidad de Sevilla. Departamento de Farmacología |
Publication Date | 2024-05-16 |
Deposit Date | 2024-06-10 |
Published in |
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Abstract | Background: The inflammasome is a cytosolic multiprotein complex associated with multiple autoimmune diseases. Phytochemical compounds in soy (Glycine max) foods, such as isoflavones, have been reported for their ... Background: The inflammasome is a cytosolic multiprotein complex associated with multiple 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 µM) or EQ (5, 10, and 25 µM), followed by LPS stimulation. The levels of PGE2, NO, TNF-α, IL-6, and IL-1β 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-κB, 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-κB due to the binding of DZ or EQ, which is translated into decreased TNF-α, 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-1β and IL-18 activation. |
Funding agencies | Ministerio de Economía y Competitividad (MINECO). España Junta de Andalucía Instituto Politécnico Nacional, Mexico Consejo Nacional de Ciencia y Tecnología (CONACYT). México |
Project ID. | AGL-2017-89342-P
CTS-259 20171085 20181622 20232041 20160204 CB254600 PDCPN-782 |
Citation | Márquez Flores, Y.K., Martínez Galero, E., Correa Basurto, J., Sixto López, Y., Villegas Lama, I., Rosillo Ramírez, M.d.l.Á.,...,Alarcón de la Lastra Romero, C. (2024). Daidzein and Equol: Ex Vivo and In Silico Approaches Targeting COX-2, iNOS, and the Canonical Inflammasome Signaling Pathway. Pharmaceuticals, 17 (5), 647. https://doi.org/10.3390/ph17050647. |
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