Direito, RosaRocha, JoãoMelo, Inês Alves deGonçalves, MargaridaDuarte, Maria PaulaFernandes, AdelaideSepodes, BrunoFigueira, Maria-Eduardo2025-10-212025-10-212025-120367-326XPURE: 132574966PURE UUID: ce8174b8-119b-4a48-bed8-4db8eb90bfa8Scopus: 105016322959PubMed: 40962152WOS: 001583900300001ORCID: /0000-0002-0940-519X/work/194835199http://hdl.handle.net/10362/189590Publisher Copyright: © 2025Background: This study is the first to evaluate a phenolic extract of Salvia officinalis in the TNBS murine model of colitis. Inflammatory bowel disease (IBD) involves transmural oxidative and nitrosative stress that up-regulates inducible nitric-oxide synthase (iNOS) and cyclo‑oxygenase-2 (COX-2). Although phenolic constituents of S. officinalis are anti-inflammatory in vitro, their efficacy has never been tested in the trinitrobenzene-sulphonic acid (TNBS) model of colitis. Methods: Aqueous-ethanolic sage leaves were extracted and standardized [(total phenolics = 6208 ± 200 mg gallic acid equivalent (GAE) L−1; rosmarinic acid = 1.4 g/L). Male CD-1 mice received intracolonic TNBS (2.5 % w/v, 100 μL). Two hours later, and once daily for four days, they were gavaged with vehicle or sage extract (15 mg phenolic acids kg−1). Disease-activity index, colon length, macroscopic and histological scores, iNOS/COX-2 immunostaining, and survival (Kaplan-Meier) were recorded. Results: Extract markedly attenuated TNBS injury: diarrhea score fell from 3.0 ± 0.0 to 0.3 ± 0.2, ulcer length from 3.6 ± 0.1 cm to 0.8 ± 0.2 cm, and colon shortening was prevented (11.8 ± 0.2 to 12.9 ± 0.2 cm). Mortality dropped from 36 % to 0 %. Histology improved (score 3 to 1) and iNOS, COX-2 over-expression was normalized (4.25 to 2.19-fold and 2.48 to 1.03-fold, respectively). Ancillary paw-edema and cell-migration assays confirmed anti-inflammatory activity without indicating anti-metastatic effects. Conclusions: The extract given orally affords the first demonstrated protection against acute TNBS colitis, normalizing key inflammatory markers and abolishing procedure-related mortality. Sage phenolics indicate promising multitarget leads for IBD therapy, meriting chronic-model and pharmacokinetic evaluation.123104314engColitisCOX-2IBDiNOSProliferationRosmarinic acidPharmacologyPlant ScienceDrug DiscoveryHorticultureSDG 3 - Good Health and Well-beingjournal article10.1016/j.fitote.2025.106870https://www.scopus.com/pages/publications/105016322959https://www.webofscience.com/wos/woscc/full-record/WOS:001583900300001