{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T05:18:34Z","timestamp":1787894314478,"version":"build-2784847793"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Ulcerative colitis (UC) is a chronic relapsing inflammatory bowel disease characterized by mucosal immune imbalance, epithelial barrier disruption, and intestinal dysbiosis. Curcumol (CUR) possesses anti-inflammatory and immunomodulatory activities; however, the multilevel mechanisms underlying its protective effects against dextran sulfate sodium (DSS)-induced UC remain incompletely understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A mouse model of UC was established in C57BL\/6J mice using 3% DSS. CUR or 5-aminosalicylic acid (5-ASA) was administered once daily beginning on the first day of DSS exposure, with 5-ASA serving as a phenotypic positive control. The protective effects of CUR were evaluated based on body weight change, disease activity index (DAI), colon length, histopathological alterations, inflammatory cytokine levels, and barrier-related molecules. Based on the pharmacodynamic and phenotypic evaluation, the high-dose CUR group was selected for subsequent mechanistic studies, including fecal 16S rRNA gene sequencing, fecal untargeted metabolomics, colonic transcriptome sequencing, analysis of public human UC transcriptomic datasets, and integrative network pharmacology, followed by experimental validation of key candidate molecules.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>CUR significantly ameliorated DSS-induced body weight loss, reduced DAI scores, preserved colon length, and alleviated histopathological injury. CUR also decreased the levels of TNF-\u03b1, IL-1\u03b2, IL-6, and IL-17, restored goblet cell abundance, and partially restored the protein expression of MUC2, claudin-1, ZO-1, and occludin. Moreover, these protective effects were generally more pronounced in the high-dose CUR group, with significant between-dose differences observed for selected endpoints (P &amp;lt; 0.05). Further exploratory analyses showed that high-dose CUR partially restored gut microbial diversity and reshaped community structure while partially reversing DSS-induced metabolic disturbances. Integrative analysis of mouse colonic transcriptomics, public human UC transcriptomic datasets, and network pharmacology converged on SPP1 and CD44 as candidate hub genes and implicated the PI3K\/Akt signaling pathway as a key candidate pathway altered by DSS exposure and modulated by CUR. Experimental validation further demonstrated that high-dose CUR reduced the expression of SPP1, CD44, and PIK3CB and decreased the p-p85\/p85 and p-Akt\/Akt ratios. Multiplex immunofluorescence further showed a reduction in the macrophage-associated fraction of SPP1-positive cells after high-dose CUR intervention.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Concurrent administration of CUR exerted protective effects in a DSS-induced mouse model of UC by reducing inflammation and mucosal barrier injury and partially normalizing gut microbial and fecal metabolic profiles. These effects were associated with attenuation of SPP1\/CD44\/PI3K\/Akt-related signaling, suggesting that this signaling network may contribute to CUR-mediated protection against DSS-induced UC.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1852138","type":"journal-article","created":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T04:33:34Z","timestamp":1787891614000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrated multi-omics, network pharmacology, and experimental validation reveal the protective mechanisms of curcumol against DSS-induced ulcerative colitis"],"prefix":"10.3389","volume":"17","author":[{"given":"Fu","family":"Shu","sequence":"first","affiliation":[{"name":"College of Pharmaceutical Sciences, Southwest University","place":["Chongqing, 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