Abstract

We have previously demonstrated that Cepharanthine improves glycemic status and reduces renal injury in streptozotocin‐induced diabetic rats via antioxidant and anti‐inflammatory mechanisms. However, the hypoglycemic mechanism of Cepharanthine remains unclear. We hypothesize that Cepharanthine reduces blood glucose in steptozotocin‐induced diabetic rats via restoring pancreatic β‐cells mass and insulin secretion. Diabetes was induced by a single i.p. injection of streptozotocin (50 mg/kg) in male Sprague Dawley rats. Control and diabetic rats were treated with Cepharanthine (10 mg/kg/day, i.p.) for six weeks (n=6–8). Cepharanthine treatment significantly reduced blood glucose levels and increased plasma insulin levels in diabetic rats (blood glucose was 290± 67 in Cepharanthine treated diabetic rats vs. 550±17 mg/dl in non‐treated diabetic rats, P<0.05). The percentage of TUNEL positive cells was significantly elevated in the pancreas of diabetic rats and these changes was reduced by Cepharanthine treatment (P<0.05). Immunohistochemcial analysis revealed a decrease in pancreatic islet‐specific glucose‐6‐phosphatase catalytic subunit related protein (IGRP) and an increase in pancreatic and duodenal homeobox 1 (PDX‐1) expression levels in Cepharanthine treated vs. non treated diabetic rats (P<0.05). Cepharanthine also improved vascular endothelial function as it significantly attenuated the impairment in aortic ring relaxation to acetylcholine in diabetic rats. Moreover, Cepharanthine reduced markers of renal injury and inflammation and slowed the progression of renal fibrosis as evidenced by the reduction in levels of albuminuria, podocalyxin excretion, renal ICAM‐1 and TGF‐β in diabetic rats. The reduction in renal inflammation and injury was associated with decreased in renal caspase 3 expression in Cepharanthine treated diabetic rats. These data suggest that Cepharanthine halts the progression of streptozotocin‐induced diabetic complications in rats via reduced pancreatic β‐cells apoptosis and increased β‐cell s maturation and subsequently insulin release probably via the regulation of the PDX‐1 and IGRP transcription factors of pancreatic β‐cells. Support or Funding Information The work was supported by bridge funding grant from Augusta University, Augusta, Georgia to Dr. Ahmed A. Elmarakby This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .