Marine Natural Product Honaucin A Attenuates Inflammation by Activating the Nrf2-ARE Pathway.
J Nat Prod
; 81(3): 506-514, 2018 03 23.
Article
en En
| MEDLINE
| ID: mdl-29215273
ABSTRACT
The cyanobacterial marine natural product honaucin A inhibits mammalian innate inflammation in vitro and in vivo. To decipher its mechanism of action, RNA sequencing was used to evaluate differences in gene expression of cultured macrophages following honaucin A treatment. This analysis led to the hypothesis that honaucin A exerts its anti-inflammatory activity through activation of the cytoprotective nuclear erythroid 2-related factor 2 (Nrf2)-antioxidant response element/electrophile response element (ARE/EpRE) signaling pathway. Activation of this pathway by honaucin A in cultured human MCF7 cells was confirmed using an Nrf2 luciferase reporter assay. In vitro alkylation experiments with the natural product and N-acetyl-l-cysteine suggest that honaucin A activates this pathway through covalent interaction with the sulfhydryl residues of the cytosolic repressor protein Keap1. Honaucin A presents a potential therapeutic lead for diseases with an inflammatory component modulated by Nrf2-ARE.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Productos Biológicos
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Transducción de Señal
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Factor 2 Relacionado con NF-E2
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Organismos Acuáticos
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Inflamación
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Antiinflamatorios
Límite:
Animals
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Female
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Humans
Idioma:
En
Revista:
J Nat Prod
Año:
2018
Tipo del documento:
Article