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The increasing emergence of anticoccidial drug resistance has intensified the search for effective plant\u2010derived alternatives. This study evaluated the in\u00a0vivo anticoccidial activity of\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Citrus sinensis<\/jats:italic>\n                    <\/jats:styled-content>\n                    leaf extract (CSLE) against\n                    <jats:italic>Eimeria papillata<\/jats:italic>\n                    infection in mice and investigated its potential molecular mechanisms through integrated transcriptomic, molecular docking, and ADMET analyses. GC\u2013MS profiling identified 43 phytochemicals, from which major compounds were prioritized based on abundance, docking affinity, active\u2010site interactions, and pharmacokinetic safety predictions. In\u00a0vivo treatment of infected C57BL\/6 mice with CSLE (150, 300, and 600\u2009mg\/kg) significantly reduced oocyst shedding in a dose\u2010dependent manner, with the highest dose decreasing counts to 9.8\u2009\u00d7\u200910\n                    <jats:sup>6<\/jats:sup>\n                    oocysts\/g and improving body weight gain and jejunal histology. Transcriptomic analysis indicated that parasite persistence was associated with suppression of host IFN\u2010\u03b3 signaling, whereas CSLE partially restored immune responsiveness. Molecular docking demonstrated strong binding of Cholestan\u20103\u2010ol, Estra\u20101,3,5(10)\u2010trien\u201017\u03b2\u2010ol, and a secoyohimban derivative to CDPK1, PKG, and HSP90, exceeding amprolium affinity. ADMET analysis supported favorable safety and pharmacokinetic properties. Overall, CSLE showed strong dose\u2010dependent anticoccidial activity through multiple mechanisms, highlighting its potential as a natural alternative for coccidiosis control.\n                  <\/jats:p>","DOI":"10.1002\/bmc.70501","type":"journal-article","created":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T09:13:48Z","timestamp":1779959628000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrative In\u00a0Vivo and Transcriptomics\u2010Guided In Silico Profiling of\n                    <scp>\n                      <i>Citrus sinensis<\/i>\n                    <\/scp>\n                    Phytochemicals as Multi\u2010Target Anticoccidial Agents"],"prefix":"10.1002","volume":"40","author":[{"given":"Esam M.","family":"Al\u2010Shaebi","sequence":"first","affiliation":[{"name":"Department of Zoology, College of Science King Saud University  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-8043-3098","authenticated-orcid":false,"given":"Seifeldin","family":"Elabed","sequence":"additional","affiliation":[{"name":"Biotechnology and Genetic Engineering Department, Faculty of Science Helwan National University  Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simeon","family":"Santourlidis","sequence":"additional","affiliation":[{"name":"Epigenetics Core Laboratory, Institute of Transplantation Diagnostics and Cell Therapeutics, Medical Faculty Heinrich\u2010Heine University D\u00fcsseldorf  D\u00fcsseldorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hend M.","family":"Alharbi","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Science Princess Nourah Bint Abdulrahman University  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1869-5800","authenticated-orcid":false,"given":"Mohamed A.","family":"Dkhil","sequence":"additional","affiliation":[{"name":"Department of Zoology and Entomology, Faculty of Science Capital University (formerly Helwan University)  Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9263-6871","authenticated-orcid":false,"given":"Rewaida","family":"Abdel\u2010Gaber","sequence":"additional","affiliation":[{"name":"Department of Zoology, College of Science King Saud University  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,28]]},"reference":[{"key":"e_1_2_12_2_1","first-page":"61","article-title":"Comparative Efficacy of Selected Anticoccidial Drugs in Ambarorow Sheep Naturally Infected with Enteric Coccidia in South Darfur, Sudan","volume":"20","author":"Abakar A. 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