title: Zerumbone protects INS-1 rat pancreatic beta cells from high glucose-induced apoptosis through generation of reactive oxygen species.
abstract: 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.
authors.affiliation: The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
authors.forename: Changyin
authors.initials: C
authors.lastname: Wang
authors.affiliation: The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
authors.forename: Shibo
authors.initials: S
authors.lastname: Zou
authors.affiliation: The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China. Electronic address: zhengjuncuichina@163.com.
authors.forename: Zhengjun
authors.initials: Z
authors.lastname: Cui
authors.affiliation: The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Guo
authors.affiliation: The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
authors.forename: Qingnan
authors.initials: Q
authors.lastname: Meng
authors.affiliation: The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
authors.forename: Xun
authors.initials: X
authors.lastname: Shi
authors.affiliation: The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Gao
authors.affiliation: The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
authors.forename: Gaoyuan
authors.initials: G
authors.lastname: Yang
authors.affiliation: The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
authors.forename: Zhaofeng
authors.initials: Z
authors.lastname: Han
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D005947:Glucose / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012717:Sesquiterpenes / Q000494:pharmacology*
chemical_list: D017382:Reactive Oxygen Species; D012717:Sesquiterpenes; C403304:zerumbone; D020928:Mitogen-Activated Protein Kinases; D005947:Glucose
keywords: Hyperglycemia; Oxidative stress; Pancreatic β cells; Survival; Zerumbone