{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T20:48:59Z","timestamp":1790023739725,"version":"4.0.1"},"reference-count":178,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,25]],"date-time":"2025-12-25T00:00:00Z","timestamp":1766620800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key R&D Program of China","doi-asserted-by":"crossref","award":["2023YFD1302004"],"award-info":[{"award-number":["2023YFD1302004"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Livestock and Poultry Breeding Industry Project of the Ministry of Agriculture and Rural Affairs","award":["19211162"],"award-info":[{"award-number":["19211162"]}]},{"name":"Horizontal Scientific Research Project of Liaocheng University","award":["K25LD167"],"award-info":[{"award-number":["K25LD167"]}]},{"name":"Liaocheng University scientific research fund","award":["318052339"],"award-info":[{"award-number":["318052339"]}]},{"name":"Shandong Province Agricultural Major Technology Collaborative Promotion Plan","award":["SDNYXTTG-2024-13"],"award-info":[{"award-number":["SDNYXTTG-2024-13"]}]},{"name":"Deanship of Research and Graduate Studies at King Khalid University for funding this work through Large Research Project","award":["RGP.2\/731\/46"],"award-info":[{"award-number":["RGP.2\/731\/46"]}]},{"name":"Liaocheng Municipal Bureau of Science and Technology, High-talented Foreign Expert Introduction Program","award":["GDWZ202401"],"award-info":[{"award-number":["GDWZ202401"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Veterinary Sciences"],"abstract":"<jats:p>This review synthesizes research on nuclear factor erythroid 2-related factor 2 (Nrf2) in intestinal health across human, livestock, and mouse models. The Nrf2 signaling pathway serves as a master regulator of cellular antioxidant defenses and a key therapeutic target for intestinal inflammatory disorders, including ulcerative colitis and Crohn\u2019s disease. The interplay between oxidative stress, Nrf2 signaling, and NF-\u03baB inflammatory cascades represents a critical axis in the pathogenesis and resolution of intestinal inflammation. Under normal physiological conditions, Nrf2 remains sequestered in the cytoplasm by Kelch-like ECH-associated protein 1 (Keap1), which facilitates its ubiquitination and proteasomal degradation. However, during oxidative stress, reactive oxygen species (ROS) and electrophilic compounds modify critical cysteine residues on Keap1, disrupting the Keap1-Nrf2 interaction and enabling Nrf2 nuclear translocation. Once in the nucleus, Nrf2 binds to antioxidant response elements (ARE) in the promoter regions of genes encoding phase II detoxifying enzymes and antioxidant proteins, including heme oxygenase-1 (HO-1), NAD(P)H quinone oxidoreductase 1 (NQO1), and glutamate-cysteine ligase. This comprehensive review synthesizes current evidence demonstrating that activation of Nrf2 signaling confers protection against intestinal inflammation through multiple interconnected mechanisms: suppression of NF-\u03baB-mediated pro-inflammatory cascades, enhancement of cellular antioxidant capacity, restoration of intestinal barrier integrity, modulation of immune cell function, and favorable alteration of gut microbiota composition. We systematically examine a diverse array of therapeutic agents targeting Nrf2 signaling, including bioactive peptides, natural polyphenols, flavonoids, terpenoids, alkaloids, polysaccharides, probiotics, and synthetic compounds. The mechanistic insights and therapeutic evidence presented underscore the translational potential of Nrf2 pathway modulation as a multi-targeted strategy for managing intestinal inflammatory conditions and restoring mucosal homeostasis.<\/jats:p>","DOI":"10.3390\/vetsci13010025","type":"journal-article","created":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T00:50:21Z","timestamp":1766710221000},"page":"25","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Therapeutic Agents Targeting the Nrf2 Signaling Pathway to Combat Oxidative Stress and Intestinal Inflammation in Veterinary and Translational Medicine"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5890-2996","authenticated-orcid":false,"given":"Muhammad Zahoor","family":"Khan","sequence":"first","affiliation":[{"name":"College of Agriculture and Biology, Liaocheng University, Liaocheng 252000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuhuan","family":"Li","sequence":"additional","affiliation":[{"name":"College of Agriculture and Biology, Liaocheng University, Liaocheng 252000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6839-7849","authenticated-orcid":false,"given":"Abd","family":"Ullah","sequence":"additional","affiliation":[{"name":"College of Agriculture and Biology, Liaocheng University, Liaocheng 252000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Li","sequence":"additional","affiliation":[{"name":"College of Agriculture and Biology, Liaocheng University, Liaocheng 252000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed","family":"Abohashrh","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences, College of Applied Medical Sciences, King Khalid University, Abha 61421, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6930-5214","authenticated-orcid":false,"given":"Fuad M.","family":"Alzahrani","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratories Sciences, College of Applied Medical Sciences, Taif University, Taif 21944, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6688-0106","authenticated-orcid":false,"given":"Khalid J.","family":"Alzahrani","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratories Sciences, College of Applied Medical Sciences, Taif University, Taif 21944, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8156-2069","authenticated-orcid":false,"given":"Khalaf F.","family":"Alsharif","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratories Sciences, College of Applied Medical Sciences, Taif University, Taif 21944, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changfa","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Agriculture and Biology, Liaocheng University, Liaocheng 252000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingshan","family":"Ma","sequence":"additional","affiliation":[{"name":"College of Agriculture and Biology, Liaocheng University, Liaocheng 252000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S71","DOI":"10.1093\/ibd\/izae020.155","article-title":"Inflammatory bowel disease in youth under 20 from 1990\u20132019: A global perspective on regional and national variations from the gbd 2019 analysis","volume":"30","author":"Patel","year":"2024","journal-title":"Inflamm. 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