Food Science and Technology Program, Beijing Normal University-Hong Kong Baptist University United International College, Zhuhai, 519087, China; Laboratory and Clinical Research Institute for Pain, Department of Anaesthesiology, The University of Hong Kong, Hong Kong, China.
Life Science Division, SRM Research Institute, SRM Institute of Science and Technology, Kattankulathur, Tamilnadu, 603 203, India.
Eur J Pharmacol. 2020 Dec 5;888:173606. doi: 10.1016/j.ejphar.2020.173606. Epub 2020 Sep 24.
Chronic hyperglycemia induces pancreatic β-cell dysfunction through several cell signaling pathways. The β-cell loss by apoptosis appears to play a crucial role in the onset and progression of diabetes. This study was aimed to investigate the role of vitexin against high glucose-induced β-cells apoptosis and the underlying mechanisms involved therein. INS-1 cells were pretreated with vitexin (20 and 40 μM) followed by high glucose (33 mM) exposure and the cytotoxicity was assessed by MTT. The effect of vitexin on nuclear factor erythroid 2-related factor 2 (Nrf2) and NF-kB signaling molecules have been studied. Vitexin-mediated stimulation of Nrf2 was assessed. Vitexin protected the cells against high glucose toxicity in a concentration-dependent manner. Vitexin improved insulin signaling as analyzed by the levels of functional proteins in the insulin pathways, viz., insulin receptor (IR), insulin receptor substrate (IRS)-1 and IRS-2, glucose transporter -2, and glucose-stimulated insulin secretion. Vitexin improved the high glucose-induced nuclear transcription factor system by suppressing Rel A, Rel B, P50/p105, and IκB expression resulting in decreased cell apoptosis, further confirmed by the reduction in the percentage of Annexin-V positive cells. Our data suggest that vitexin improves insulin secretion by activating key proteins, including NF-κB and Nrf2 in β-cells regulating apoptosis.
慢性高血糖通过多种细胞信号通路诱导胰岛β细胞功能障碍。细胞凋亡导致的β细胞丢失似乎在糖尿病的发生和进展中起着关键作用。本研究旨在探讨圣草素（vitexin）对高糖诱导的β细胞凋亡的作用及其潜在机制。用圣草素（20 和 40 μM）预处理 INS-1 细胞，然后暴露于高葡萄糖（33 mM）下，通过 MTT 评估细胞毒性。研究了圣草素对核因子红细胞 2 相关因子 2（Nrf2）和 NF-κB 信号分子的影响。评估了圣草素介导的 Nrf2 刺激作用。圣草素以浓度依赖的方式保护细胞免受高葡萄糖毒性。圣草素通过增加胰岛素信号通路中功能性蛋白的水平来改善胰岛素信号，这些蛋白包括胰岛素受体（IR）、胰岛素受体底物（IRS）-1 和 IRS-2、葡萄糖转运体-2 和葡萄糖刺激的胰岛素分泌。圣草素通过抑制 Rel A、Rel B、P50/p105 和 IκB 的表达，抑制核转录因子系统，从而减少细胞凋亡，进一步通过减少 Annexin-V 阳性细胞的百分比得到证实。我们的数据表明，圣草素通过激活 NF-κB 和 Nrf2 等关键蛋白，改善β细胞中调节细胞凋亡的胰岛素分泌。
