Enhancement of glyoxalase 1, a polyfunctional defense enzyme, by quercetin in the brain in streptozotocin-induced diabetic rats

Xia Zhu, Ya-qin Cheng, Qian Lu, Lei Du, Xiao-xing Yin, Yao-wu Liu

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.