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The key characteristics observed in UC patients involve fecal urgency, abdominal discomfort, and bloody diarrhea, all of which significantly lower their quality of life. Preclinical studies investigated the protective effect of minocycline in animal models of colitis. This study aimed to assess minocycline\u2019s potential efficacy and safety in mesalamine-treated UC patients. This randomized, controlled pilot clinical research included 46 individuals with mild to moderate UC who met the inclusion criteria. The mesalamine group (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200923) received 1\u00a0g of mesalamine three times a day for 6\u00a0months. The minocycline group (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200923) received minocycline 100\u00a0mg twice daily and mesalamine 1\u00a0g three times a day. Patients were evaluated by a gastroenterologist using the Short Inflammatory Bowel Disease Questionnaire (SIBDQ), Truelove and Witts Severity Index, Brief Pain Inventory (BPI), and the non-invasive Partial Mayo Score (PMS). Before and after 6\u00a0months of treatment, each patient\u2019s levels of nitric oxide (NO), matrix metalloproteinase-12 (MMP-12), and intracellular adhesion molecule 1 (ICAM-1) were measured. Serum levels of MMP-12, ICAM-1, and NO were statistically lower in the minocycline group than in the mesalamine group. In the minocycline group, the Truelove and Witts Severity Index, PMS, and BPI pain intensity all significantly dropped, whereas SIBDQ was substantially elevated compared to the mesalamine group. Minocycline could serve as a potential adjunctive remedy for enhancing clinical outcomes, improving quality of life, and modulating inflammation in patients with mild to moderate UC.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Trial registration<\/jats:bold>\n                    : ClinicalTrials.gov ID: NCT06201793. Trial registration date 22\u20131-2024.\n                  <\/jats:p>","DOI":"10.1007\/s00210-025-04662-2","type":"journal-article","created":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T07:18:45Z","timestamp":1761203925000},"page":"4555-4568","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Repurposing minocycline as an added-on treatment for ulcerative colitis patients on mesalamine: a randomized clinical pilot study"],"prefix":"10.1007","volume":"399","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-4224-8255","authenticated-orcid":false,"given":"Amira F.","family":"Mashaly","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sahar K.","family":"Hegazy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monir M.","family":"Bahgat","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,10,23]]},"reference":[{"key":"4662_CR1","doi-asserted-by":"publisher","first-page":"1162","DOI":"10.1016\/0016-5085(90)90329-Y","volume":"98","author":"I Ahnfelt-R\u00f8nne","year":"1990","unstructured":"Ahnfelt-R\u00f8nne I, Nielsen OH, Christensen A, Langholz E, Binder V, Riis P (1990) Clinical evidence supporting the radical scavenger mechanism of 5-aminosalicylic acid. 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