Ameliorative Effects of the White Jade Snail Secretion on DSS-Induced Ulcerative Colitis in Mice

Ulcerative colitis (UC) is a chronic relapsing inflammatory bowel disease with limited effective treatment options. The White Jade Snail Secretion (WJSS) is a biologically rich natural product with considerable therapeutic potential. UPLC–MS/MS analysis of WJSS against a standard compound spectral library and LC–MS/MS characterization of its purified protein fraction led to the identification of 88 small-molecule compounds and 782 peptide sequences, respectively. Network pharmacology analysis uncovered 240 common targets between WJSS and UC, enriched in key inflammatory pathways. A Dextran Sulfate Sodium (DSS)-induced mouse model of ulcerative colitis was employed to evaluate WJSS efficacy. WJSS treatment dose-dependently attenuated body weight loss, disease activity index elevation, and colon shortening, alongside significantly reduced histopathological scores. Mechanistically, WJSS suppressed NF-κB signaling, downregulating pro-inflammatory cytokines IL-6, TNF-α, and IL-1β. Furthermore, WJSS restored the expression of tight junction proteins (Occludin, ZO-1) and the mucin MUC2, thereby preserving intestinal barrier integrity. 16S rRNA sequencing revealed that WJSS reshaped the gut microbiota by enriching beneficial taxa (Unclassified-f-Lachnospiraceae) and reducing pathogenic taxa (Campylobacter, Helicobacter). Overall, WJSS alleviates DSS-induced UC through anti-inflammatory, barrier-protective, and microbiota-modulatory action, mediated by its peptides and small-molecule constituents. This study provides a multi-target mechanistic foundation for WJSS as a promising natural therapeutic candidate for UC, facilitating its clinical translation and natural product development.