Guaianolides from Achillea millefolium L. and their anti-inflammatory activity.
Phytochemistry
; 210: 113647, 2023 Jun.
Article
en En
| MEDLINE
| ID: mdl-36963706
ABSTRACT
Seven previously undescribed guaianolides, millefolactons A-G, and three known analogues, millefoliumins A-C, were isolated from the whole plant of Achillea millefolium L. growing in Xinjiang, China. Their structures were elucidated using the HR-ESI-MS and NMR data analyses. The absolute configurations of millefolactons A-G were determined by single-crystal X-ray crystallography, ECD data analysis, and quantum-chemical ECD calculations. Millefolactons A-E are rare 3-oxa-guaianolides. Millefolacton C, millefolacton E, millefoliumin A and millefoliumin B exhibited enzymatic inhibition of 15-LOX. Molecular docking simulations were conducted to visualize interactions between the four active compounds and 15-LOX and determine binding mechanisms. Moreover, a LPS-induced BV2 cell model was used to further investigate the anti-inflammatory mechanism of millefolacton C. As a result, millefolacton C significantly inhibited NO release, repressed levels of pro-inflammatory cytokines including TNF-α, IL-18, PGE2 and IL-6, and inhibited the protein expression of iNOS and COX2 proteins. In addition, millefolacton C could potently decreased the expression of NLRP3, ASC, and IL-1ß proteins in LPS-stimulated BV2 cells. These results indicate that the 3-oxa-guaianolides from A. millefolium L. offer great potential as leads for anti-inflammatory drug development.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Achillea
Idioma:
En
Revista:
Phytochemistry
Año:
2023
Tipo del documento:
Article