{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:08:12Z","timestamp":1785434892069,"version":"3.56.0"},"reference-count":240,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical University of Silesia, Katowice, Poland"},{"id":[{"id":"https:\/\/ror.org\/005k7hp45","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Colitis involves both local intestinal damage and systemic dysfunction, driven by oxidative stress and immune imbalance. Histamine, acting through its receptors, influences these processes, yet its therapeutic relevance in colitis remains unclear. This review systematically examines histamine-mediated signaling in colitic inflammation and evaluates preclinical and clinical data on antihistamines to assess their potential as a mechanism-based treatment. Methods: A structured literature search was conducted using PubMed and Google Scholar to identify studies addressing histamine signaling and the use of antihistamines in colitis, using keywords such as \u201ccolitis,\u201d \u201chistamine,\u201d \u201chistamine receptors,\u201d and \u201cantihistamines.\u201d Relevant experimental and clinical studies were screened and critically analyzed to provide an integrated overview of mechanistic and therapeutic insights. This review was designed as a mechanistic narrative synthesis based on a structured search and qualitative appraisal rather than a formal systematic review with quantitative risk-of-bias grading. Results: Findings from preclinical investigations consistently indicate that pharmacological manipulation of histamine signaling\u2014especially through H3 and H4 receptor subtypes\u2014reduces inflammatory activity and modulates oxidative balance in animal models of colitis. Conversely, clinical evidence concerning H1 and H2 receptor antagonists remains scarce and discordant, lacking sufficient support for a definitive causal relationship or unambiguous therapeutic efficacy. Importantly, no clinical studies to date have assessed the effects of selective H3 or H4 receptor blockers in individuals with colitis, revealing a substantial disconnect between bench research and bedside application. Existing human trials have mainly concentrated on mucosal endpoints, with little attention paid to systemic manifestations or oxidative stress-related parameters. Conclusions: Histamine-dependent signaling constitutes a mechanistically credible target in colitis, connecting immune activation, impairment of the epithelial barrier, and oxidative injury. Although experimental data are encouraging, clinical corroboration remains absent. Antihistamines may hold greater promise for alleviating systemic oxidative stress than for directly ameliorating intestinal inflammation. Rigorously designed clinical trials that incorporate both gastrointestinal and systemic outcome measures are necessary to elucidate their therapeutic position.<\/jats:p>","DOI":"10.3390\/ph19071124","type":"journal-article","created":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T10:35:52Z","timestamp":1784630152000},"page":"1124","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Use of Antihistamine Drugs in Colitis: A Review"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-1574-8562","authenticated-orcid":false,"given":"Bartosz","family":"Bogielski","sequence":"first","affiliation":[{"name":"Branch in Bielsko-Bia\u0142a, Medical University of Silesia, 40-055 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3655-2461","authenticated-orcid":false,"given":"Dariusz","family":"Gach","sequence":"additional","affiliation":[{"name":"Scientific Research Facility, Branch in Bielsko-Bia\u0142a, Medical University of Silesia, 40-055 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1809-9531","authenticated-orcid":false,"given":"Katarzyna","family":"Michalczyk","sequence":"additional","affiliation":[{"name":"Branch in Bielsko-Bia\u0142a, Medical University of Silesia, 40-055 Katowice, Poland"},{"name":"Department of Physiology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 40-055 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bronis\u0142awa","family":"Skrzep-Poloczek","sequence":"additional","affiliation":[{"name":"Branch in Bielsko-Bia\u0142a, Medical University of Silesia, 40-055 Katowice, Poland"},{"name":"Scientific Research Facility, Branch in Bielsko-Bia\u0142a, Medical University of Silesia, 40-055 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8868-9495","authenticated-orcid":false,"given":"Mateusz","family":"Stojko","sequence":"additional","affiliation":[{"name":"Scientific Research Facility, Branch in Bielsko-Bia\u0142a, Medical University of Silesia, 40-055 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3879-6548","authenticated-orcid":false,"given":"Jolanta","family":"Zalejska-Fiolka","sequence":"additional","affiliation":[{"name":"Branch in Bielsko-Bia\u0142a, Medical University of Silesia, 40-055 Katowice, Poland"},{"name":"Department of Biochemistry, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 40-055 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8509-7507","authenticated-orcid":false,"given":"Dominika","family":"Stygar","sequence":"additional","affiliation":[{"name":"Branch in Bielsko-Bia\u0142a, Medical University of Silesia, 40-055 Katowice, Poland"},{"name":"Department of Physiology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 40-055 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,21]]},"reference":[{"key":"ref_1","first-page":"1795","article-title":"Colitides","volume":"16","author":"Tortora","year":"2012","journal-title":"Eur. 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