{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T05:22:51Z","timestamp":1792041771167,"version":"4.4.0"},"reference-count":54,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T00:00:00Z","timestamp":1772755200000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"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":["Archiv der Pharmazie"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Indicaxanthin, a prominent betalain pigment known for its bioactivity and safety, has long been valued in traditional medicine for its antioxidant and anti\u2010inflammatory effects. The leading cause of liver failure and dysfunction is hepatic ischemia\u2013reperfusion (I\/R) injury, which frequently happens during hemorrhagic shock, hepatectomy, and liver transplantation. Given the increasing global incidence of hepatic disorders, especially those involving ischemic damage and inflammation\u2010mediated apoptosis, there is a pressing need for therapeutic agents that can target key molecular pathways. Liver ischemia and injury often result in the upregulation of inflammatory cascades, notably involving NF\u2010\u03baB p65, and pro\u2010apoptotic markers such as caspase\u20103, both of which play central roles in hepatocellular injury. We constructed a protein\u2013protein interaction (PPI) network integrating predicted indicaxanthin targets with liver ischemia\u2010related proteins. The network identified NF\u2010\u03baB p65 and caspase\u20103 as central hubs, functionally associated with pro\u2010inflammatory and apoptotic pathways. Gene Ontology and KEGG enrichment analyses further implicated TNF, IL\u201017, and Toll\u2010like receptor pathways, highlighting the broader regulatory role of indicaxanthin in hepatic stress signaling. Molecular docking against NF\u2010\u03baB p65 (RelA) revealed a strong binding affinity (\u22126.89\u2009kcal\/mol), with key hydrogen bond interactions involving Lys221, Arg246, Val244, and Gln241. Subsequent molecular dynamics (MD) simulations confirmed the structural stability of the complex, showing low RMSD drift, consistent hydrogen bonding, compact ligand behavior, and favorable energy profiles over 100\u2009ns. Furthermore, hepatic IRI was induced in male Wistar rats, and then the hepatoprotective effect of indicaxanthin was studied at histopathological, molecular, and biochemical levels.<\/jats:p>","DOI":"10.1002\/ardp.70219","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T12:24:00Z","timestamp":1772972640000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Indicaxanthin Mitigates Hepatic Ischemia Reperfusion Injury in Rats via Bax\/Bcl\u20102 Modulation: Experimental Evidence Supported by Molecular Docking and Dynamics Simulation"],"prefix":"10.1002","volume":"359","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7008-1836","authenticated-orcid":false,"given":"Mahmoud","family":"Abdelnaser","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Faculty of Pharmacy Deraya University Minia Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abeer H.","family":"Elmaidomy","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy Beni\u2010Suef University Beni\u2010Suef Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mina Ezzat","family":"Attya","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Medicine Minia University Minia Egypt"},{"name":"Department of Pathology, Faculty of Medicine Minia National University New Minia Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1746-1631","authenticated-orcid":false,"given":"Faisal H.","family":"Altemani","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences University of Tabuk Tabuk Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naseh A.","family":"Algehainy","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences University of Tabuk Tabuk Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad A.","family":"Alanazi","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences University of Tabuk Tabuk Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdullah H.","family":"Altemani","sequence":"additional","affiliation":[{"name":"Department of Family and Community Medicine, Faculty of Medicine University of Tabuk Tabuk Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Usama Ramadan","family":"Abdelmohsen","sequence":"additional","affiliation":[{"name":"Deraya Center for Scientific Research Deraya University Minia Egypt"},{"name":"Department of Pharmacognosy Faculty of Pharmacy, Minia University Minia 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