Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, China.
Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou, China.
Aging (Albany NY). 2020 Apr 20;12(8):7015-7029. doi: 10.18632/aging.103059.
Studies have shown that diabetes is an important risk factor for cognitive dysfunction, also called diabetic encephalopathy (DE). Quercetin has been reported to be effective in improving cognitive dysfunction in DE. But its detailed mechanism is still ambiguous. In this study, we used db/db mice to investigate whether quercetin could activate SIRT1 and inhibit ER pathways to improve DE. Behavioral tests (Morris water maze and new objects) showed that quercetin (70 mg/kg) can effectively improve the learning and memory ability in db/db mice. OGTT and ITT tests indicated that quercetin could alleviate impaired glucose tolerance and insulin resistance in db/db mice. Western blot analysis and Nissl staining showed that quercetin can improve the expression of nerve and synapse-associated proteins (PSD93, PSD95, NGF and BDNF) and inhibit neurodegeneration. Meanwhile, quercetin up-regulates SIRT1 protein expression and inhibits the expression of ER signaling pathway-related proteins (PERK, IRE-1α, ATF6, eIF2α, BIP and PDI). In addition, oxidative stress levels were significantly reduced after quercetin treatment. In conclusion, current experimental results indicated that SIRT1/ER stress is a promising mechanism involved in quercetin-treated diabetic encephalopathy.
研究表明，糖尿病是认知功能障碍（又称糖尿病性脑病，DE）的一个重要危险因素。槲皮素已被报道可有效改善 DE 中的认知功能障碍。但其详细机制仍不清楚。在这项研究中，我们使用 db/db 小鼠来研究槲皮素是否可以通过激活 SIRT1 和抑制 ER 通路来改善 DE。行为学测试（Morris 水迷宫和新物体识别测试）表明，槲皮素（70mg/kg）可有效改善 db/db 小鼠的学习和记忆能力。OGTT 和 ITT 测试表明，槲皮素可改善 db/db 小鼠的葡萄糖耐量受损和胰岛素抵抗。Western blot 分析和尼氏染色显示，槲皮素可改善神经和突触相关蛋白（PSD93、PSD95、NGF 和 BDNF）的表达并抑制神经退行性变。同时，槲皮素上调 SIRT1 蛋白表达并抑制 ER 信号通路相关蛋白（PERK、IRE-1α、ATF6、eIF2α、BIP 和 PDI）的表达。此外，槲皮素处理后氧化应激水平显著降低。综上所述，目前的实验结果表明，SIRT1/ER 应激可能是槲皮素治疗糖尿病性脑病的一种有前途的机制。
