{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T05:54:28Z","timestamp":1781848468628,"version":"3.54.5"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T00:00:00Z","timestamp":1781827200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background\/Objectives<\/jats:title>\n                    <jats:p>We have previously demonstrated that the natural alkaloid Cepharanthine (Ceph) reduces renal injury in streptozotocin (STZ)-induced insulin-deficient diabetic rats via antioxidant and anti-inflammatory mechanisms. However, the hypoglycemic mechanism of Ceph remains unclear. We hypothesize that Ceph reduces blood glucose in STZ-induced insulin-deficient diabetic rats via restoring pancreatic \u03b2-cells function and insulin secretion.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Diabetes was induced in male Sprague-Dawley rats by a single intraperitoneal injection of STZ (50\u00a0mg\/kg, i. p). Rats with blood glucose \u2265250\u00a0mg\/dL were confirmed to be diabetic. Rats were randomly assigned to four groups (n = 6\/group): Control, Control + Ceph, Diabetic, and Diabetic + Ceph. Rats were treated with either vehicle or Ceph (10\u00a0mg\/kg\/day, i. p) for 6\u00a0weeks. Pancreatic \u03b2-cell integrity was evaluated using TUNEL assay and pancreatic duodenal homeobox 1 (PDX-1) immunofluorescence. Aortic rings vascular reactivity was assessed using wire myography, and renal function was determined by measuring creatinine clearance, albuminuria, and podocalyxin excretion. Renal inflammation and fibrosis were quantified via ELISA assessment of ICAM-1 and TGF-\u03b2 and Masson\u2019s trichrome staining.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Ceph treatment significantly reduced blood glucose levels and increased plasma insulin levels in diabetic rats. The % TUNEL\n                      <jats:sup>+<\/jats:sup>\n                      cells were significantly elevated in the pancreas of diabetic rats, and Ceph treatment reduced these changes. Immunofluorescence analysis also revealed an increase in PDX-1 expression levels in Ceph treated vs. non treated diabetic rats. Ceph improved vascular endothelial function as it significantly attenuated the impairment in aortic ring relaxation to acetylcholine in diabetic rats. Moreover, Ceph significantly reduced markers of renal injury as evidenced by the reduction in albuminuria and podocalyxin excretion levels and the improvement in creatinine clearance in diabetic rats. Ceph also reduced renal oxidative stress, inflammation, and fibrosis as evidence by the reduction in Thiobarbituric Acid Reactive Substances (TBARs) excretion, and renal ICAM-1 and TGF-\u03b2 levels in diabetic rats, respectively.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These data suggest that Ceph halts the progression of diabetic nephropathy in rats not only via its antioxidant and anti-inflammatory properties but also via the reduction in pancreatic \u03b2-cells apoptosis and increased \u03b2-cells integrity in STZ-induced insulin-deficient diabetic male Sprague-Dawley rats.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1807706","type":"journal-article","created":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T05:46:06Z","timestamp":1781847966000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Cepharanthine improves blood glucose levels and mitigates renal injury in streptozotocin-induced diabetic rats via restoring pancreatic \u03b2-cell integrity and reducing inflammation"],"prefix":"10.3389","volume":"17","author":[{"given":"Mohamed A.","family":"Katary","sequence":"first","affiliation":[{"name":"Department of Oral Biology, Dental College of Georgia, Augusta University","place":["Augusta, GA, United States"]},{"name":"Department of Pharmacology & Toxicology, Faculty of Pharmacy, Damanhour University","place":["Damanhour, Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yara A.","family":"Samra","sequence":"additional","affiliation":[{"name":"Department of Oral Biology, Dental College of Georgia, Augusta University","place":["Augusta, GA, United States"]},{"name":"Department of Biochemistry, Faculty of Pharmacy, Mansoura University","place":["Mansoura, Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karim M.","family":"Saad","sequence":"additional","affiliation":[{"name":"Department of Oral Biology, Dental College of Georgia, Augusta University","place":["Augusta, GA, United States"]},{"name":"Department of Pharmacology & Toxicology, Faculty of Pharmacy, Mansoura University","place":["Mansoura, Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim","family":"Capehart","sequence":"additional","affiliation":[{"name":"Department of General Dentistry, Dental College of Georgia, Augusta University","place":["Augusta, GA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafik","family":"Abdelsayed","sequence":"additional","affiliation":[{"name":"Department of Pathology & Diagnostic Sciences, Dental College of Georgia, Augusta University","place":["Augusta, GA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed A.","family":"Elmarakby","sequence":"additional","affiliation":[{"name":"Department of Oral Biology, Dental College of Georgia, Augusta University","place":["Augusta, GA, United States"]},{"name":"Department of Pharmacology & Toxicology, Faculty of Pharmacy, Mansoura University","place":["Mansoura, Egypt"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,19]]},"reference":[{"key":"B1","first-page":"1445","article-title":"Diabetic nephropathy--a review of the natural history, burden, risk factors and treatment","volume":"96","author":"Ayodele","year":"2004","journal-title":"J. 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