Abstract: In this study, Zizania latifolia shell extract (Zlse) was obtained by ethanol extraction and silica gel chromatography, and its effect on ulcerative colitis in mice was evaluated. The underlying mechanism was analyzed by network pharmacology. Six groups of mice were established: normal control (NC), model control (MC), positive control (PC), low-dose Zlse (Zlse-L), medium-dose Zlse (Zlse-M) and high-dose Zlse (Zlse-H). Ulcerative colitis was induced by intragastric administration of 3.5% sodium dextran sulfate solution in the MC, PC and Zlse groups. The PC and Zlse groups were intragastrically administrated with mesalazine and Zlse, respectively. The NC and MC groups were intragastrically administrated with 0.5% sodium carboxymethylcellulose (CMC-Na) solution. The health status of mice was recorded daily, and the disease activity index (DAI) score was calculated. The percentage body mass change, DAI score, colon length, hematoxylin and eosin (HE)-stained colonic sections, colonic histopathology score, serum inflammatory factors (IL-6, IL-8, IL-1β, and TNF-α) levels, and the activities of colonic myeloperoxidase (MPO) and superoxide dismutase (SOD) were compared between the six groups. Based on the key targets and the important Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways obtained from the GeneCards, OMIM, TTD and DAVID databases, a ‘active ingredient-target-KEGG pathway’ network diagram was constructed. The results showed that compared with the MC group, the trend of body mass loss in the Zlse treatment groups was significantly slowed down (P < 0.05), the colon length was restored, and the colon injury was reduced. In addition, the levels of serum proinflammatory factors in the Zlse groups were significantly decreased (P < 0.05); colonic MPO activity was significantly decreased (P < 0.05), while SOD activity was increased (P < 0.05). Eight active components, 77 intersection targets and 119 KEGG pathways were obtained by network pharmacology analysis. The key active components were tricin and tricin-4’-O-syringyl alcohol, and the important pathways included the P13K/Akt signaling pathway, receptor activation and reactive oxygen species accumulation, which were confirmed by animal experiments. The results showed that Zlse can concentration-dependently prevent DSS-induced ulcerative colitis in mice by inhibiting the release of proinflammatory factors and regulating the antioxidant defense capacity of the colon.

Key words: Zizania latifolia shell; network pharmacology; tricin; ulcerative colitis