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However, these effects may be associated with increased incidence of nephrotoxicity. This work aimed to the exploration of the impact of omarigliptin with or without shikonin on a rodent model of cyclosporine nephrotoxicity and the precise determination of the mechanisms that may represent the basis of these effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In a Wistar rat model of cyclosporine-elicited nephrotoxicity, the effect of omarigliptin and shikonin, each alone and in combination, was determined at the level of the biochemical parameters and the histomorphological changes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Omarigliptin and\/or shikonin administered to cyclosporine-injected animals induced a significant restoration of renal functions and glucagon-like peptide-1 (GLP-1) and augmentation of the antioxidant defenses, associated with increased sirtuin 1 expression and its related signaling changes in comparison to animals that received cyclosporine alone. Additionally, omarigliptin and\/or shikonin elicited a significant amelioration of the inflammatory response and cellular differentiation and a significant improvement of the renal tissue disruptive changes elicited by cyclosporine. These effects were evident with omarigliptin\/shikonin combination when compared to the groups treated with each agent alone.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Omarigliptin\/shikonin combination suggests potential therapeutic benefit for the mitigation of cyclosporine nephrotoxicity, possibly via their effects on dipeptidyl peptidase 4 activity and GLP-1 levels with subsequent modulation of the redox status, cellular proliferation, and the inflammatory pathways.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/09603271251394693","type":"journal-article","created":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T22:53:51Z","timestamp":1761951231000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":2,"title":["Omarigliptin\/shikonin combination alleviates cyclosporine-induced nephrotoxicity: The role of sirtuin 1, glucagon-like peptide-1, HMGB1\/RAGE\/TLR4 signaling, and p38\/ERK\/JNK MAPKs"],"prefix":"10.1177","volume":"44","author":[{"given":"Marwa H.","family":"Abdallah","sequence":"first","affiliation":[{"name":"University of Ha'il"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanan Abdelmawgoud","family":"Atia","sequence":"additional","affiliation":[{"name":"University of Ha'il"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hemat A.","family":"Elariny","sequence":"additional","affiliation":[{"name":"University of Ha'il"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amany M.","family":"Khalifa","sequence":"additional","affiliation":[{"name":"University of Ha'il"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asmaa","family":"Saleh","sequence":"additional","affiliation":[{"name":"Princess Nourah Bint Abdulrahman 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