Zerumbone protects INS-1 rat pancreatic beta cells from high glucose-induced apoptosis through generation of reactive oxygen species

The aim of this study is to explore the effect of zerumbone, a natural sesquiterpene isolated from Zingiber zerumbet Smith, on high glucose-induced cytotoxicity in pancreatic β cells. INS-1 rat pancreatic β cells were treated with 33 mM glucose with or without different concentrations of zerumbone and cell viability and apoptosis were assessed. The involvement of reactive oxygen species (ROS) and mitogen-activated protein kinase (MAPK) signaling in the action of zerumbone was examined. Notably, zerumbone significantly (P < 0.05) prevented the reduction of cell viability induced by high glucose. Such protection was in a concentration-dependent fashion up to 60 μM of zerumbone. Annexin-V/propidium iodide staining analysis showed that zerumbone impaired the apoptotic response of high glucose-treated INS-1 cells, which was coupled with a significant decline in cleaved caspase-3 and caspase-9. Pretreatment with the ROS inhibitor N-acetylcysteine abrogated the phosphorylation of p38 and JNK induced by high glucose. Zerumbone significantly (P < 0.05) decreased the generation of ROS and the phosphorylation of p38 and JNK MAPKs in high glucose-treated INS-1 cells. Pharmacological activation of p38 and JNK with anisomycin reversed the anti-apoptotic effect of zerumbone. Additionally, simultaneous inhibition of p38 and JNK significantly (P < 0.05) reduced the apoptotic response in high glucose-treated INS-1 cells. In conclusion, zerumbone confers protection against high glucose-induced apoptosis of INS-1 pancreatic β cells, largely through interfering with ROS production and p38 and JNK activation. Zerumbone may have potential therapeutic effects against hyperglycemia-induced β cell damage in diabetes.