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Ligustilide, a major component derived from\n                    <jats:italic toggle=\"yes\">Angelica sinensis<\/jats:italic>\n                    (Oliv.) Diels, exerts anti-inflammation effect. However, its impact and molecular mechanism on colitis remain obscure. In this study, in\u00a0vivo and in\u00a0vitro experiments verified that ligustilide protected against colitis by suppressing macrophage-mediated inflammation and repairing intestinal barrier. Of note, we utilized a thermal proteome profiling strategy to preliminarily find early growth response factor 1 (EGR1) as a target of ligustilide. Cellular thermal shift assay, drug affinity responsive target stability, and surface plasmon resonance analysis revealed that ligustilide directly targeted His386 to bind to EGR1. Furthermore, RNA-sequencing, dual luciferase reporter gene assay, and rescue experiments illustrated that ligustilide disturbed the nuclear translocation of EGR1 and broke its combination with a disintegrin and metalloproteinase 17 (ADAM17) promoter, thereby inhibiting ADAM17 transcription and downstream tumor necrosis factor-\u03b1 (TNF-\u03b1) production, as well as expression of inflammatory proteins cyclooxygenase 2 and inducible nitric oxide synthase. Finally, the in\u00a0vivo experiment with EGR1 overexpression proved that EGR1 was essential for the protective effects of ligustilide on colitis mice. Taken together, our study demonstrates that ligustilide targets EGR1 to inhibit the EGR1-ADAM17-TNF\u03b1 pathway, thus alleviating macrophage-mediated intestinal inflammation and restoring gut barrier.\n                  <\/jats:p>","DOI":"10.34133\/research.0864","type":"journal-article","created":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T05:06:02Z","timestamp":1754543162000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark_01","source":"Crossref","is-referenced-by-count":9,"title":["Ligustilide Suppresses Macrophage-Mediated Intestinal Inflammation and Restores Gut Barrier via EGR1-ADAM17-TNF-\u03b1 Pathway in Colitis Mice"],"prefix":"10.34133","volume":"8","author":[{"given":"Yanyang","family":"Li","sequence":"first","affiliation":[{"name":"School of Pharmaceutical Sciences, \rGuangzhou University of Chinese Medicine, Guangzhou 510006, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yequn","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, \rGuangzhou University of Chinese Medicine, Guangzhou 510006, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Liang","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, \rGuangzhou University of Chinese Medicine, Guangzhou 510006, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peiqi","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, \rGuangzhou University of Chinese Medicine, Guangzhou 510006, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shihua","family":"Xu","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, \rGuangzhou University of Chinese Medicine, Guangzhou 510006, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumei","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, \rGuangzhou University of Chinese Medicine, Guangzhou 510006, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Perioperative Research Centre of Chinese Medicine, \rthe Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510120, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xudong","family":"Zhu","sequence":"additional","affiliation":[{"name":"Markey Cancer Center, \rUniversity of Kentucky, Lexington, KY 40536, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaozhan","family":"Lin","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, \rGuangzhou University of Chinese Medicine, Guangzhou 510006, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Yu","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, \rGuangzhou University of Chinese Medicine, Guangzhou 510006, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3206-782X","authenticated-orcid":true,"given":"Hailin","family":"Tang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, \rSun Yat-sen University Cancer Center, Guangzhou 510060, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","published-online":{"date-parts":[[2025,9,2]]},"reference":[{"issue":"9","key":"e_1_3_4_2_2","doi-asserted-by":"crossref","first-page":"2211","DOI":"10.1016\/j.cgh.2022.06.030","article-title":"Global hospitalization trends for Crohn\u2019s disease and ulcerative colitis in the 21st century: A systematic review with temporal analyses","volume":"21","author":"Buie MJ","year":"2023","unstructured":"Buie MJ, Quan J, Windsor JW, Coward S, Hansen TM, King JA, Kotze PG, Gearry RB, Ng SC, Mak JWY, et al. 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