Abstract
Glyoxalase 1 (Glo-1) is an ubiquitous cellular enzyme that participates in the detoxification of methylglyoxal (MG), a cytotoxic byproduct of glycolysis that induces protein modification (advanced glycation end products [AGEs]), oxidative stress, and inflammation. The concentration of MG is elevated under high-glucose conditions, such as diabetes. Therefore, Glo-1 and MG have been implicated in the pathogenesis of diabetic encephalopathy. We investigated the effect of quercetin on brain damage that was caused by diabetes in rats and the mechanisms associated with Glo-1. Streptozotocin-induced diabetic rats were treated orally with quercetin (30, 60, and 90 mg/kg) or distilled water for 14 weeks. The temporal cortex and hippocampus were harvested and analyzed for different indices assays. Quercetin, especially at a high dose, increased the levels of reduced glutathione and the activity of superoxide dismutase and decreased the levels of AGEs, the receptor for AGEs (RAGE), and malondialdehyde in the diabetic brain. Quercetin also significantly decreased the levels of inflammatory markers (cyclooxygenase-2, interleukin-1β, and tumor necrosis factor α) in diabetic brains. Most importantly, Glo-1 activity and protein expression were increased in quercetin-treated diabetic rat brains compared with untreated diabetic brains. These results indicate that quercetin exerts beneficial effects by decreasing protein glycation, oxidative stress, and inflammation through the upregulation of Glo-1, which may ameliorate diabetic encephalopathy.
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The work was supported through funding from the National Natural Science Foundation of China (81371210), China, and the Priority Academic Program Development of Jiangsu Higher Education Institutions, China.
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LY and YX conceived and designed research. ZX and LY were responsible for the data analysis and draft of the manuscript. ZX, CY, and LQ contributed to the acquisition of animal data. DL was responsible for purchasing reagents. All authors read and approved the manuscript.
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All animal experiments were performed in accordance with the license by Jiangsu Province Science and Technology Office (Nanjing, China) and the approval from the Animal Ethics Committee of Xuzhou Medical University (2014008). All experiments were conformed to the Guidelines for Ethical Conduct in the Care and Use of Animals. Every effort was made to minimize stress to the animals.
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Zhu, X., Cheng, Yq., Lu, Q. et al. Enhancement of glyoxalase 1, a polyfunctional defense enzyme, by quercetin in the brain in streptozotocin-induced diabetic rats. Naunyn-Schmiedeberg's Arch Pharmacol 391, 1237–1245 (2018). https://doi.org/10.1007/s00210-018-1543-z
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DOI: https://doi.org/10.1007/s00210-018-1543-z