Discovery, Preliminary Structure–Activity Relationship, and Evaluation of Oleanane-Type Saponins from Pulsatilla chinensis for the Treatment of Ulcerative Colitis

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.