Daidzein and Equol: Ex Vivo and In Silico Approaches Targeting COX-2, iNOS, and the Canonical Inflammasome Signaling Pathway

• Published in: Pharmaceuticals (Basel, Switzerland) Vol. 17; no. 5; p. 647
• Main Authors: Márquez-Flores, Yazmín K, Martínez-Galero, Elizdath, Correa-Basurto, José, Sixto-López, Yudibeth, Villegas, Isabel, Rosillo, María Á, Cárdeno, Ana, Alarcón-de-la-Lastra, Catalina
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01-05-2024
• Subjects: Adapter proteins; Analysis; Anti-inflammatory drugs; Arthritis; Autoimmunity; Cellular signal transduction; Chemokines; Cytokines; daidzein; Diabetes; Disease; docking; Enzymes; equol; Homeostasis; Identification and classification; inflammasome; inflammation; Inflammatory bowel disease; Isoflavones; Nitric oxide; Physiological aspects; Protein expression; Rheumatoid arthritis; Rheumatoid factor; soy; Testing; Type 2 diabetes; Canada; Germany; Spain; Mexico; daidzein; docking; equol; soy; inflammation; inflammasome
• ISSN: 1424-8247; 1424-8247
• DOI: 10.3390/ph17050647

The inflammasome is a cytosolic multiprotein complex associated with multiple autoimmune diseases. Phytochemical compounds in soy (
) foods, such as isoflavones, have been reported for their anti-inflammatory properties.
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.
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 PGE
, 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.
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.
This study establishes that DZ and EQ inhibit LPS-induced inflammatory responses in peritoneal murine macrophages via down-regulation of NO and PGE
generation, as well as the inhibition of the canonical inflammasome pathway, regulating NLRP3, and consequently decreasing IL-1β and IL-18 activation.