{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T13:08:08Z","timestamp":1788872888731,"version":"build-2803163510"},"reference-count":100,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T00:00:00Z","timestamp":1770940800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T00:00:00Z","timestamp":1770940800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Phytotherapy Research"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Crocin (CRO) is an antioxidant carotenoid extracted from the\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Crocus sativus<\/jats:italic>\n                    <\/jats:styled-content>\n                    plant. CRO impacts many biological pathways related to inflammation, but its activity as an antioxidant and anti\u2010inflammatory agent against ferritinophagy\u2010associated oxidative damage and cell death in colonic mucosa is little understood. Therefore, this study predicted CRO\u2010driven protective targets and processes against ulcerative colitis (UC) using network pharmacology, docking, and experimental analysis. Network analysis and molecular docking were used to analyze CRO and UC targets and pathways. To test the pharmacological efficacy of CRO in\u00a0vivo, 24 rats were separated into four groups: Cont, UC, mesalazine (100\u2009mg\/kg), and CRO (40\u2009mg\/kg). Rats received oral treatments for 8\u2009days before UC induction. A single intrarectal injection of 2\u2009mL acetic acid (AA) caused UC in rats. Estimated DAI and colonic protein content. Oxidant\/antioxidant status and inflammatory markers ULK1, FTH\u20101, Beclin\u20101, GPX4, NCOA4, and SLC7A11 were also evaluated. Additionally, western blot was used to measure mTOR, AKT, and LC3B protein. Both histopathological and immunohistochemical studies were done. The network showed 228 CRO\u2010UC targets, including CASP3 in the top 10 targets. AKT2 and MAP1LC3B were 56th and 63rd, respectively. The top 30 markedly enhanced KEGG pathways included \u201cPathways in cancer\u201d and \u201cKaposi sarcoma\u2010associated herpesvirus infection\u201d. Docking confirmed CRO's significant binding affinity for ULK1, FRIH, GPX4, and SLC7A11. In\u00a0vivo, CRO pre\u2010treatment diminished ULK1, autophagic proteins (Beclin\u20101 and LC3B\u2010II\/LC3B\u2010I), and ferritinophagy\u2010related protein (NCOA4), while elevating Akt\/mTORC1, FTH\u20101, SLC7A11, and GPX4, thereby mitigating iron overload, ROS, and ferroptosis. Changing AKT\/mTORC1\/ULK1 pathway in UC pathogeneses improved colonic morphological and macroscopic abnormalities in CRO\u2010treated rats. This study suggests that CRO may reduce ferritinophagy\u2010induced colonic oxidative damage in rats via modulating AKT\/mTORC1\/ULK1. Ferritinophagy as an attractive therapeutic target in different experimental and clinical conditions deserves further investigation.\n                  <\/jats:p>","DOI":"10.1002\/ptr.70189","type":"journal-article","created":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T03:12:38Z","timestamp":1771038758000},"page":"2288-2315","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Crocin Modulates\n                    <scp>AKT<\/scp>\n                    \/\n                    <scp>mTORC1<\/scp>\n                    \/\n                    <scp>ULK1<\/scp>\n                    Cascade to Attenuate Ferritinophagy\u2010Induced Colonic Oxidative Injury in Ulcerative Colitis: Network Pharmacology, Molecular Docking, and Experimental Validation"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9058-1800","authenticated-orcid":false,"given":"Mamdouh A.","family":"Oraby","sequence":"first","affiliation":[{"name":"Pharmacology and Toxicology Department, Faculty of Pharmacy Badr University in Cairo (BUC)  Badr Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sherif S.","family":"Abdel Mageed","sequence":"additional","affiliation":[{"name":"Pharmacology and Toxicology Department, Faculty of Pharmacy Badr University in Cairo (BUC)  Badr Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2759-1001","authenticated-orcid":false,"given":"Mohammed S.","family":"Elballal","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Pharmacy Badr University in Cairo (BUC)  Badr Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanallah","family":"El\u2010Bahrawy","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Veterinary Medicine University of Sadat City  Menoufia Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henwa M.","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Pharmacy Badr University in Cairo (BUC)  Badr Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menna M.","family":"Ayoub","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy Egyptian Russian University  Badr Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasser M.","family":"Moustafa","sequence":"additional","affiliation":[{"name":"Pharmacology and Toxicology Department, Faculty of Pharmacy Badr University in Cairo (BUC)  Badr Cairo Egypt"},{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy Suez Canal University  Ismailia Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1462-0716","authenticated-orcid":false,"given":"Maram Mohammed","family":"El Tabaa","sequence":"additional","affiliation":[{"name":"Department of Medical Physiology, Faculty of Medicine Tanta University  Gharbia Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3607-770X","authenticated-orcid":false,"given":"Manar Mohammed","family":"El Tabaa","sequence":"additional","affiliation":[{"name":"Pharmacology &amp; Environmental Toxicology, Environmental Studies &amp; Research Institute (ESRI) University of Sadat City  Menoufia Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,13]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.INTIMP.2023.110138"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/1472\u20106882\u201014\u201049"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.TAAP.2020.114919"},{"key":"e_1_2_12_5_1","volume-title":"Bancroft's Theory and Practice of Histological Techniques","author":"Bancroft J. 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