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.