Inhibitory Potential of the Drimane Sesquiterpenoids Isotadeonal and Polygodial in the NF-kB Pathway
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 t...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-03-01
|
| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/30/7/1555 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849730180107468800 |
|---|---|
| author | Víctor Marín Cecilia Villegas Ayorinde Víctor Ogundele Jaime R. Cabrera-Pardo Bernd Schmidt Cristian Paz Viviana Burgos |
| author_facet | Víctor Marín Cecilia Villegas Ayorinde Víctor Ogundele Jaime R. Cabrera-Pardo Bernd Schmidt Cristian Paz Viviana Burgos |
| author_sort | Víctor Marín |
| collection | DOAJ |
| description | 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 <i>Drimys winteri</i>, a medicinal tree of the Mapuche people in Chile. Isotadeonal, or epi-polygodial, was obtained from polygodial by epimerization in basic media (60% yield, Na<sub>2</sub>CO<sub>3</sub>, 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. |
| format | Article |
| id | doaj-art-6a16d173f6284920afa6ee791a433bc3 |
| institution | DOAJ |
| issn | 1420-3049 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj-art-6a16d173f6284920afa6ee791a433bc32025-08-20T03:08:57ZengMDPI AGMolecules1420-30492025-03-01307155510.3390/molecules30071555Inhibitory Potential of the Drimane Sesquiterpenoids Isotadeonal and Polygodial in the NF-kB PathwayVíctor Marín0Cecilia Villegas1Ayorinde Víctor Ogundele2Jaime R. Cabrera-Pardo3Bernd Schmidt4Cristian Paz5Viviana Burgos6Laboratory of Natural Products & Drug Discovery, Center CEBIM, Department of Basic Sciences, Faculty of Medicine, Universidad de La Frontera, Temuco 4780000, ChileDepartamento de Ciencias Biológicas y Químicas, Facultad de Recursos Naturales, Universidad Católica de Temuco, Rudecindo Ortega, Temuco 4780000, ChileLaboratory of Natural Products & Drug Discovery, Center CEBIM, Department of Basic Sciences, Faculty of Medicine, Universidad de La Frontera, Temuco 4780000, ChileLaboratorio de Química Aplicada y Sustentable (LabQAS), Departamento de Química, Universidad del Bío-Bío, Avenida Collao 1202, Concepcion 4051381, ChileInstitut für Chemie, Universität Potsdam, Karl-Liebknecht-Str. 24-25, D-14476 Potsdam, GermanyLaboratory of Natural Products & Drug Discovery, Center CEBIM, Department of Basic Sciences, Faculty of Medicine, Universidad de La Frontera, Temuco 4780000, ChileEscuela de Tecnología Médica, Facultad de Salud, Universidad Santo Tomás, Temuco 4780000, ChileInflammation 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 <i>Drimys winteri</i>, a medicinal tree of the Mapuche people in Chile. Isotadeonal, or epi-polygodial, was obtained from polygodial by epimerization in basic media (60% yield, Na<sub>2</sub>CO<sub>3</sub>, 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.https://www.mdpi.com/1420-3049/30/7/1555drimane sesquiterpenoidspolygodialisotadeonal<i>Drimys winteri</i>NF-κB |
| spellingShingle | Víctor Marín Cecilia Villegas Ayorinde Víctor Ogundele Jaime R. Cabrera-Pardo Bernd Schmidt Cristian Paz Viviana Burgos Inhibitory Potential of the Drimane Sesquiterpenoids Isotadeonal and Polygodial in the NF-kB Pathway Molecules drimane sesquiterpenoids polygodial isotadeonal <i>Drimys winteri</i> NF-κB |
| title | Inhibitory Potential of the Drimane Sesquiterpenoids Isotadeonal and Polygodial in the NF-kB Pathway |
| title_full | Inhibitory Potential of the Drimane Sesquiterpenoids Isotadeonal and Polygodial in the NF-kB Pathway |
| title_fullStr | Inhibitory Potential of the Drimane Sesquiterpenoids Isotadeonal and Polygodial in the NF-kB Pathway |
| title_full_unstemmed | Inhibitory Potential of the Drimane Sesquiterpenoids Isotadeonal and Polygodial in the NF-kB Pathway |
| title_short | Inhibitory Potential of the Drimane Sesquiterpenoids Isotadeonal and Polygodial in the NF-kB Pathway |
| title_sort | inhibitory potential of the drimane sesquiterpenoids isotadeonal and polygodial in the nf kb pathway |
| topic | drimane sesquiterpenoids polygodial isotadeonal <i>Drimys winteri</i> NF-κB |
| url | https://www.mdpi.com/1420-3049/30/7/1555 |
| work_keys_str_mv | AT victormarin inhibitorypotentialofthedrimanesesquiterpenoidsisotadeonalandpolygodialinthenfkbpathway AT ceciliavillegas inhibitorypotentialofthedrimanesesquiterpenoidsisotadeonalandpolygodialinthenfkbpathway AT ayorindevictorogundele inhibitorypotentialofthedrimanesesquiterpenoidsisotadeonalandpolygodialinthenfkbpathway AT jaimercabrerapardo inhibitorypotentialofthedrimanesesquiterpenoidsisotadeonalandpolygodialinthenfkbpathway AT berndschmidt inhibitorypotentialofthedrimanesesquiterpenoidsisotadeonalandpolygodialinthenfkbpathway AT cristianpaz inhibitorypotentialofthedrimanesesquiterpenoidsisotadeonalandpolygodialinthenfkbpathway AT vivianaburgos inhibitorypotentialofthedrimanesesquiterpenoidsisotadeonalandpolygodialinthenfkbpathway |