14th Congress of the Middle East Society for Organ Transplantation and the 5th Middle East Transplant GamesIschemia-reperfusion injury5,7-Dihydroxy-3,4,6-Trimethoxyflavone Attenuates Ischemic Damage and Apoptosis in Mouse Islets

•5,7-dihydroxy-3,4,6-trimethoxyflavone (Eupatilin), one of the major pharmacologically active compounds found in the Artemisia species, has been reported to exert antioxidative, anti-inflammatory, and antiapoptotic activities, and it also enhances insulin secretion.•Eupatilin administration has not been applied to the islet transplant model.•Treatment with eupatilin enhanced glucose-induced insulin secretion. The GSH levels were significantly elevated in the eupatilin-treated group.•Eupatilin-treated islets attenuated expression of NO, iNOS, caspase-3, and apoptosis. These results suggest that preoperative eupatilin administration enhanced islet function before transplantation and attenuated cytokine-induced damage associated with NO production and apoptosis.

BackgroundThe transplantation of isolated pancreatic islets is a promising treatment for diabetes. 5,7-dihydroxy-3,4,6-trimethoxyflavone (Eupatilin), a pharmacologically active flavone derived from the Artemisia plant species, has been reported to have antioxidant and anti-inflammatory activities. This study examines the hypothesis that preoperative eupatilin treatment can attenuate ischemic damage and apoptosis before islet transplantation.MethodsIslets isolated from Balb/c mice were randomly divided into 2 groups, and cultured in medium supplemented with or without eupatilin. In vitro islet viability and function were assessed. After treatment with a cytokine cocktail consisting of tumor necrosis factor (TNF)-α, interferon (INF)-γ, and interleukin (IL)-1β, islet cell viability, function, and apoptotic status were determined. The glutathione (GSH) and nitrous oxide (NO) levels were also measured. Proteins related to apoptosis were analyzed using Western blotting.ResultsThere was no difference in cell viability between the 2 groups. Islets cultured in the medium supplemented with eupatilin showed 1.4-fold higher glucose-induced insulin secretion than the islets cultured in the medium without eupatilin. After treatment with a cytokine cocktail, glucose-induced insulin release and the total insulin content of the islets were significantly improved in eupatilin-pretreated islets compared with islets not treated with eupatilin. Apoptosis was significantly decreased, and GSH levels were elevated in the eupatilin-pretreated group. Cytokine-only treated islets produced significantly higher levels of NO, iNOS, and caspase-3 than islets pretreated with eupatilin before cytokine treatment.ConclusionsThese results suggest that preoperative eupatilin administration enhances islet function before transplantation and attenuates the cytokine-induced damage associated with NO production and apoptosis.