Discovery, Preliminary Structure-Activity Relationship, and Evaluation of Oleanane-Type Saponins from Pulsatilla chinensis for the Treatment of Ulcerative Colitis.
J Med Chem
; 66(5): 3635-3647, 2023 03 09.
Article
em En
| MEDLINE
| ID: mdl-36843292
ABSTRACT
To discover ulcerative colitis (UC) treatment agents, 28 oleanane-type triterpenoid saponins (1-28) including three new saponins, pulsatillosides P-R (1-3), were isolated from Pulsatilla chinensis. The isolated saponins could observably ameliorate UC by improving the intestinal epithelial cell barrier and intestinal flora in vivo. The structure-activity relationship indicated that the oligosaccharide chain at C-28 was essential for their anti-UC activities; the methyl group at the C-23 site of triterpene saponins showed important effects on anti-UC efficacy; the chain length of oligosaccharides at position C-28 had little effect on their anti-UC activities. In vivo investigation of representative saponins 1 and 13 further confirmed that 23-methyl-3,28-bisdesmosidic oleanane-type saponins inhibited the TNFα-NFκB-MLCK axis to improve the intestinal epithelial cell barrier of the colon in UC mice. These findings revealed the potential of 23-methyl-3,28-bisdesmosidic oleanane-type saponins from P. chinensis as promising candidates for the treatment of UC.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Saponinas
/
Colite Ulcerativa
/
Pulsatilla
Limite:
Animals
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article