Structural elucidation of an active pectin against inflammatory bowel disease from the roots of Sanguisorba officinalis and its protection effect.

Inflammatory bowel disease (IBD) induces irreversible intestinal damage and is a pivotal risk factor for colorectal cancer. Sanguisorba officinalis extracts have been shown to alleviate intestinal inflammation, yet their underlying structural basis is still elusive. Hence, we proposed that the polysaccharide from Sanguisorba officinalis may exert a potential anti-inflammation activity for IBD. Herein, the structure of an active pectin 147-02-S2 (88.37 kDa), featuring a backbone of rhamnogalacturonan-I and xylogalacturonan, isolated from Sanguisorba officinalis roots was elucidated. Its branches, composed of 5-α-Araf, 3, 5-α-Araf, 2, 4-α-Rhap, 4-β-Galp, 6-β-Galp, 3, 6-β-Galp, terminal (t)-β-Manp, t-α-Araf, t-α-GalpA, and t-β-Galp were substituted at O-4 of rhamnose, while t-β-Xylp was located at O-3 of galacturonic acid. In vitro bioactivity assays revealed that 147-02-S2 suppressed the release of TNF-α and IL-1β in LPS-stimulated NCM460 cells. And 147-02-S2 further alleviated symptoms in mice with DSS-induced colitis. Mechanistically, 147-02-S2 inhibited the activation of TLR4/MyD88 and p38/ERK signaling cascades, while simultaneously blocking the nuclear translocation of NF-κB, thereby suppressing the secretion of pro-inflammatory cytokines. These findings suggest that 147-02-S2 might serve as a lead compound in the pursuit of novel IBDs therapies.