{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T21:45:06Z","timestamp":1781559906774,"version":"3.54.5"},"reference-count":74,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T00:00:00Z","timestamp":1742342400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Research Funding Center at Assiut University, Egypt"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diseases"],"abstract":"<jats:p>Background: Chronic inflammation and immune dysregulation are key drivers of diabetes complications. Rivaroxaban (RX) and sitagliptin (SITA) are established therapies for thromboembolism and glycemic control, respectively. This study evaluated the novel therapeutic potential of nano-rivaroxaban (NRX) alone and in combination with sitagliptin (SITA) in mitigating inflammation and restoring immune balance in streptozotocin (STZ)-induced diabetic rats. Methods: Type 2 diabetes was induced in rats using a single injection of STZ (60 mg\/kg). Animals were divided into five groups: control, STZ-diabetic, RX-treated (5 mg\/kg), NRX-treated (5 mg\/kg), and NRX+SITA-treated (5 mg\/kg + 10 mg\/kg). After 4 weeks of treatment, blood glucose, coagulation markers, pro-inflammatory cytokines (TNF-\u03b1, IL-1\u03b2, IL-6), and anti-inflammatory cytokines (IL-35, TGF-\u03b21, IL-10) were analyzed. Histopathological examination of the liver, kidney, pancreas, and spleen was conducted. Immunohistochemistry was used to assess hepatic NF-\u03baB expression. Results: STZ significantly elevated pro-inflammatory cytokines (IL-1\u03b2, TNF-\u03b1, IL-6) and anti-inflammatory cytokines (IL-35, TGF-\u03b21, IL-10), along with increased hepatic NF-\u03baB expression and histopathological abnormalities in immune organs. NRX significantly reduced inflammatory cytokines, improved histopathological changes in organs, and decreased hepatic NF-\u03baB expression. The combination therapy (NRX + SITA) achieved superior immune modulation, with enhanced cytokine profile restoration, reduced hepatic NF-\u03baB expression, and near-complete histopathological normalization. Conclusions: This study underscores the promise of combining nanoparticle-based drug delivery with established therapies like sitagliptin to achieve superior immune modulation and inflammation control, presenting a potential therapeutic strategy for managing diabetes complications.<\/jats:p>","DOI":"10.3390\/diseases13030087","type":"journal-article","created":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T07:48:37Z","timestamp":1742370517000},"page":"87","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Immunomodulatory Effect of Rivaroxaban Nanoparticles Alone and in Combination with Sitagliptin on Diabetic Rat Model"],"prefix":"10.3390","volume":"13","author":[{"given":"Mohamed M.","family":"Elbadr","sequence":"first","affiliation":[{"name":"Department of Medical Pharmacology, Faculty of Medicine, Assiut University, Assiut 71515, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heba A.","family":"Galal","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Veterinary Medicine, Assiut University, Assiut 71515, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helal F.","family":"Hetta","sequence":"additional","affiliation":[{"name":"Division of Microbiology, Immunology and Biotechnology, Department of Natural Products and Alternative Medicine, Faculty of Pharmacy, University of Tabuk, Tabuk 71491, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7964-1294","authenticated-orcid":false,"given":"Hassabelrasoul","family":"Elfadil","sequence":"additional","affiliation":[{"name":"Division of Microbiology, Immunology and Biotechnology, Department of Natural Products and Alternative Medicine, Faculty of Pharmacy, University of Tabuk, Tabuk 71491, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fawaz E.","family":"Alanazi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Tabuk, Tabuk 71491, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shereen","family":"Fawzy","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Faculty of Medicine, University of Tabuk, Tabuk 71491, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5333-6956","authenticated-orcid":false,"given":"Hashim M.","family":"Aljohani","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taibah University, Madina 41477, Saudi Arabia"},{"name":"Department of Pathology and Laboratory Medicine, College of Medicine, University of Cincinnati, Cincinnati, OH 45221, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noura H.","family":"Abd Ellah","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Badr University in Assiut, Naser City 2014101, Assiut, Egypt"},{"name":"Department of Pharmaceutics, Faculty of Pharmacy, Assiut University, Assiut 71515, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marwa F.","family":"Ali","sequence":"additional","affiliation":[{"name":"Department of Pathology and Clinical Pathology, Faculty of Veterinary Medicine, Assiut University, Assiut 71515, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4021-7904","authenticated-orcid":false,"given":"Ahmed K.","family":"Dyab","sequence":"additional","affiliation":[{"name":"Department of Medical Parasitology, Faculty of Medicine, Assiut University, Assiut 71515, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esraa A.","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Medical Pharmacology, Faculty of Medicine, Assiut University, Assiut 71515, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/j.thromres.2011.11.052","article-title":"Diabetes mellitus and thrombosis","volume":"129","author":"Vazzana","year":"2012","journal-title":"Thromb. 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