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穿心莲内酯衍生物AL-1对高糖诱导的RIN-m细胞氧化应激的保护作用

Protective effects of andrographolide derivative AL-1 on high glucose-induced oxidative stress in RIN-m cells.

作者信息

Yan Hui, Li Yongmei, Yang Yali, Zhang Zaijun, Zhang Gaoxiao, Sun Yewei, Yu Pei, Wang Yuqiang, Xu Lipeng

机构信息

Institute of New Drug Research and Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine, Jinan University College of Pharmacy, Guangzhou 510632, China.

出版信息

Curr Pharm Des. 2016;22(4):499-505. doi: 10.2174/1381612821666150921110716.

Abstract

AL-1 is a novel andrographolide derivative synthesized by conjugating andrographolide and alpha lipoic acid. AL-1 has been found to increase insulin secretion, decrease blood glucose level and protect β-cell mass and function in alloxan-induced diabetic mouse model. However, the protective mechanism of AL-1 on high glucose-induced pancreatic β-cell injury is still not clear. In the present study, we found that AL-1 reduced reactive oxygen species (ROS) and nitric oxide (NO) generation induced by high glucose in RIN-m cells, and which elevated the activities of superoxide dismutase (SOD) and catalase (CAT). In addition, AL-1 increased the expression of NF-E2-related factor 2 (Nrf2), thioredoxin-1 (Trx-1) and heme oxygenase-1 (HO- 1) proteins in RIN-m cells. These results suggest that AL-1 prevented RIN-m cells from high glucose-induced oxidative damage via upregulation of Nrf2 signaling pathway.

摘要

AL-1是一种通过将穿心莲内酯与α硫辛酸共轭合成的新型穿心莲内酯衍生物。在四氧嘧啶诱导的糖尿病小鼠模型中,已发现AL-1可增加胰岛素分泌、降低血糖水平并保护β细胞数量和功能。然而,AL-1对高糖诱导的胰腺β细胞损伤的保护机制仍不清楚。在本研究中,我们发现AL-1可减少高糖在RIN-m细胞中诱导产生的活性氧(ROS)和一氧化氮(NO),并提高超氧化物歧化酶(SOD)和过氧化氢酶(CAT)的活性。此外,AL-1可增加RIN-m细胞中NF-E2相关因子2(Nrf2)、硫氧还蛋白-1(Trx-1)和血红素加氧酶-1(HO-1)蛋白的表达。这些结果表明,AL-1通过上调Nrf2信号通路来防止RIN-m细胞受到高糖诱导的氧化损伤。

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