Inhibitory Potential of the Drimane Sesquiterpenoids Isotadeonal and Polygodial in the NF-kB Pathway
2025
Marin, Victor | Villegas, Cecilia | Ogundele, Ayorinde Victor | Cabrera-Pardo, Jaime R. | Schmidt, Bernd | Paz, Cristian | Burgos, Viviana
Inflammation contributes to the onset and development of many diseases, including neurodegenerative diseases, caused by the activation of microglia, leading to neurological deterioration. Nuclear factor-κB (NF-κB) is one of the most relevant pathways for identifying anti-inflammatory molecules. In this study, polygodial and isotadeonal, two drimane sesquiterpene dialdehydes, were isolated from Drimys winteri, a medicinal tree of the Mapuche people in Chile. Isotadeonal, or epi-polygodial, was obtained from polygodial by epimerization in basic media (60% yield, Na₂CO₃, r/t, 24 h). Both sesquiterpenoids were evaluated on the NF-κB pathway, with the result that isotadeonal inhibited the phosphorylation of IκB-α at 10 µM with higher potency by Western blotting. The final inhibition of the pathway was evaluated using a SEAP reporter (secreted alkaline phosphatase) on THP-1 cells. Isotadeonal inhibited SEAP with higher potency than polygodial, quercetin, and CAPE (phenethyl ester of caffeic acid). In silico analysis suggests that the α-aldehyde of isotadeonal adopts a more stable conformation in the active pocket of IκB-α than polygodial. © 2025 Elsevier B.V., All rights reserved.
Show more [+] Less [-]polygodial, isotadeonal, pathway, diseases, drimane, were, sesquiterpenoids
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