Laboratory of Neurochemistry and Cell Biology, Department of Biochemistry and Biophysics, Institute of Health Sciences, Federal University of Bahia, Salvador, Bahia, 40110-060, Brazil.
Sheffield Institute for Translational Neuroscience (SITraN), The University of Sheffield, 385a Glossop Road, Sheffield, S10 2HQ, UK.
Mol Biol Rep. 2021 Feb;48(2):1475-1483. doi: 10.1007/s11033-021-06145-y. Epub 2021 Jan 25.
Rutin is an important flavonoid consumed in the daily diet. It is also known as vitamin P and has been extensively investigated due to its pharmacological properties. On the other hand, neuronal death induced by glutamate excitotoxicity is present in several diseases including neurodegenerative diseases. The neuroprotective properties of rutin have been under investigation, although its mechanism of action is still poorly understood. We hypothesized that the mechanisms of neuroprotection of rutin are associated with the increase in glutamate metabolism in astrocytes. This study aimed to evaluate the protective effects of rutin with a focus on the modulation of glutamate detoxification. We used brain organotypic cultures from post-natal Wistar rats (P7-P9) treated with rutin to evaluate neural cell protection and levels of proteins involved in the glutamate metabolism. Moreover, we used cerebral cortex slices from adult Wistar rats to evaluate glutamate uptake. We showed that rutin inhibited the cell death and loss of glutamine synthetase (GS) induced by glutamate that was associated with an increase in glutamate-aspartate transporter (GLAST) in brain organotypic cultures from post-natal Wistar rats. Additionally, it was observed that rutin increased the glutamate uptake in cerebral cortex slices from adult Wistar rats. We conclude that rutin is a neuroprotective agent that prevents glutamate excitotoxicity and thereof suggest that this effect involves the regulation of astrocytic metabolism.
芦丁是一种在日常饮食中摄入的重要类黄酮。它也被称为维生素 P，由于其药理学特性，已被广泛研究。另一方面，谷氨酸兴奋性毒性诱导的神经元死亡存在于包括神经退行性疾病在内的几种疾病中。芦丁的神经保护特性一直在研究中，尽管其作用机制仍不清楚。我们假设芦丁的神经保护机制与星形胶质细胞中谷氨酸代谢的增加有关。本研究旨在评估芦丁的保护作用，重点关注谷氨酸解毒的调节。我们使用来自出生后第 7-9 天 Wistar 大鼠的脑器官型培养物来评估神经细胞保护和参与谷氨酸代谢的蛋白质水平。此外，我们使用来自成年 Wistar 大鼠的大脑皮质切片来评估谷氨酸摄取。我们表明，芦丁抑制了谷氨酸诱导的细胞死亡和谷氨酰胺合成酶（GS）的丢失，这与脑器官型培养物中谷氨酸-天冬氨酸转运蛋白（GLAST）的增加有关。此外，还观察到芦丁增加了成年 Wistar 大鼠大脑皮质切片中的谷氨酸摄取。我们得出结论，芦丁是一种神经保护剂，可预防谷氨酸兴奋性毒性，这表明这种作用涉及星形胶质细胞代谢的调节。
