Pyranochromones with Anti-Inflammatory Activities in Arthritis from Calophyllum membranaceum.
J Nat Prod
; 85(5): 1374-1387, 2022 05 27.
Article
em En
| MEDLINE
| ID: mdl-35503996
Eleven new pyranochromones, calomembranone A-K (1-11), two new pyranocoumarins, calopolyanolide E and F (12 and 13), together with six known analogues (14-19) were isolated from the leaves of Calophyllum membranaceum. Their structures and absolute configurations were elucidated by analysis of spectroscopic data, computational calculations, as well as X-ray crystallography of 4 and 9. The anti-inflammatory activities of all the isolates were evaluated by measuring their NO inhibitory effects in LPS-stimulated RAW 264.7 cells. Structure-activity relationships are also discussed. Compound 7 showed the strongest NO inhibition (IC50 = 0.92 µM). Oral administration of 7 dose-dependently reduced the paw swelling and downregulated neutrophil-to-lymphocyte ratio in the carrageenan-induced acute arthritis mice model. Molecular dynamics simulation and cellular thermal shift assay results indicated that 7 participated in a robust and stable interaction with the active site of TLR4. Compound 7 also suppressed the inflammation in arthritis through the regulation of TLR4 mediated signal transduction via IKK/NF-κB signaling pathway and the consequent reduction of IL-2, IL-4, and IL-5.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Artrite
/
Calophyllum
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Nat Prod
Ano de publicação:
2022
Tipo de documento:
Article