13,14-seco withaphysalins from Physalis minima and their inhibitory effects on NLRP3 inflammasome activation.
Bioorg Chem
; 151: 107630, 2024 Oct.
Article
en En
| MEDLINE
| ID: mdl-39059073
ABSTRACT
Seven new 13,14-seco withaphysalins including two new skeletons (1 and 9) were isolated from the whole plants of Physalis minima, together with three known analogues (6-8). Among them, compound 1 was an extremely rare steroid with a 6, 8-cyclo ring. Their structures were established by extensive analysis of spectroscopic data, experimental electronic circular dichroism measurements, and single-crystal X-ray crystallographic analysis. In Raw264.7 cells, compounds 1-3, 5, 6, and 8 demonstrated potent ability to reduce the NLRP3-dependent caspase-1 activation. Among these compounds, 1 and 2 showed a superior potential, consistently concentration-dependent downregulating NLRP3-dependent proinflammatory cytokine IL-1ß production in macrophage. Mechanistically, compounds 1 and 2 reduced the cleavage of caspase-1 and GSDMD, and exhibited no obvious impact both on the NF-κB activation and the expression of NLRP3 and IL-1ß, suggesting that the compounds target the activation of the NLRP3 pathway mainly by inhibiting the NLRP3 inflammasome activation step rather than the priming step.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Physalis
/
Inflamasomas
/
Proteína con Dominio Pirina 3 de la Familia NLR
Límite:
Animals
Idioma:
En
Revista:
Bioorg Chem
Año:
2024
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
Estados Unidos