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东莨菪内酯通过降低氧化应激和细胞凋亡保护 INS-1 胰腺β细胞免受糖毒性损伤。

Scopoletin protects INS-1 pancreatic β cells from glucotoxicity by reducing oxidative stress and apoptosis.

机构信息

Department of Food Science and Nutrition & Kimchi Research Institute, Pusan National University, Busan 46241, Republic of Korea.

Department of Food Science and Nutrition & Kimchi Research Institute, Pusan National University, Busan 46241, Republic of Korea.

出版信息

Toxicol In Vitro. 2023 Dec;93:105665. doi: 10.1016/j.tiv.2023.105665. Epub 2023 Aug 23.

DOI:10.1016/j.tiv.2023.105665
PMID:37619648
Abstract

This study investigated whether scopoletin could protect INS-1 pancreatic β cells from apoptosis and oxidative stress caused by high glucose. Cells were pretreated with glucose (5.5 or 30 mM) and then treated with 0, 5, 10, 25, or 50 μM Scopoletin. Cell viability and insulin secretion were measured in addition to ROS, TBARS, NO and antioxidant enzymes. Western blot analysis and flow cytometric assessment of apoptosis were also carried out. High glucose of 30 mM caused glucotoxicity and cell death in INS-1 pancreatic β cells. However, 5, 10, 25 or 50 μM scopoletin increased the level of cell viability as concentrations increased. The levels of ROS, TBARS, and NO increased by high glucose were significantly decreased after scopoletin treatment. Scopoletin also raised antioxidant enzyme activities up against oxidative stress produced by high glucose. These effects influenced the apoptosis pathway, raising levels of anti-apoptotic protein, Bcl-2, and reducing levels of pro-apoptotic proteins, including JNK, Bax, cytochrome C, and caspase 9. Annexin V/propidium staining indicated that scopoletin significantly lowered high glucose-produced apoptosis. These results indicate that scopoletin can protect INS-1 pancreatic β cells from glucotoxicity caused by high glucose and have potential as a pharmaceutical material to protect the pancreatic β cells.

摘要

本研究旨在探讨瑞香素是否能保护 INS-1 胰岛β细胞免受高糖引起的细胞凋亡和氧化应激。将细胞用葡萄糖(5.5 或 30 mM)预处理,然后用 0、5、10、25 或 50 μM 瑞香素处理。除了测定 ROS、TBARS、NO 和抗氧化酶外,还测定细胞活力和胰岛素分泌。还进行了 Western blot 分析和细胞凋亡的流式细胞术评估。30 mM 的高葡萄糖导致 INS-1 胰岛β细胞发生葡萄糖毒性和细胞死亡。然而,5、10、25 或 50 μM 瑞香素随着浓度的增加提高了细胞活力水平。瑞香素处理后,高葡萄糖引起的 ROS、TBARS 和 NO 水平显著降低。瑞香素还提高了抗氧化酶活性,对抗高葡萄糖产生的氧化应激。这些作用影响了细胞凋亡途径,提高了抗凋亡蛋白 Bcl-2 的水平,降低了促凋亡蛋白 JNK、Bax、细胞色素 C 和 caspase 9 的水平。Annexin V/PI 染色表明,瑞香素显著降低了高糖诱导的细胞凋亡。这些结果表明,瑞香素可以保护 INS-1 胰岛β细胞免受高糖引起的细胞毒性,并具有作为保护胰岛β细胞的药物的潜力。

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