Wang Changyin, Zou Shibo, Cui Zhengjun, Guo Pengfei, Meng Qingnan, Shi Xun, Gao Ya, Yang Gaoyuan, Han Zhaofeng
The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
Biochem Biophys Res Commun. 2015 May 1;460(2):205-9. doi: 10.1016/j.bbrc.2015.03.009. Epub 2015 Mar 11.
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.
本研究旨在探讨从红球姜（Zingiber zerumbet Smith）中分离出的天然倍半萜姜酮对高糖诱导的胰腺β细胞毒性作用的影响。用33 mM葡萄糖处理INS-1大鼠胰腺β细胞，同时添加或不添加不同浓度的姜酮，评估细胞活力和凋亡情况。检测了活性氧（ROS）和丝裂原活化蛋白激酶（MAPK）信号通路在姜酮作用中的参与情况。值得注意的是，姜酮显著（P < 0.05）阻止了高糖诱导的细胞活力降低。这种保护作用在姜酮浓度高达60 μM时呈浓度依赖性。膜联蛋白V/碘化丙啶染色分析表明，姜酮削弱了高糖处理的INS-1细胞的凋亡反应，同时伴随着裂解的半胱天冬酶-3和半胱天冬酶-9的显著下降。用ROS抑制剂N-乙酰半胱氨酸预处理可消除高糖诱导的p38和JNK磷酸化。姜酮显著（P < 0.05）降低了高糖处理的INS-1细胞中ROS的生成以及p38和JNK MAPKs的磷酸化。用茴香霉素对p38和JNK进行药理学激活可逆转姜酮的抗凋亡作用。此外，同时抑制p38和JNK可显著（P < 0.05）降低高糖处理的INS-1细胞的凋亡反应。总之，姜酮可保护INS-1胰腺β细胞免受高糖诱导的凋亡，主要是通过干扰ROS的产生以及p38和JNK的激活。姜酮可能对糖尿病中高血糖诱导的β细胞损伤具有潜在的治疗作用。
