Research Paper Volume 12, Issue 8 pp 7015—7029
Quercetin ameliorates diabetic encephalopathy through SIRT1/ER stress pathway in db/db mice
- 1 Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, China
- 2 Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou, China
- 3 Department of Neurology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
Received: November 3, 2019 Accepted: January 27, 2020 Published: April 20, 2020https://doi.org/10.18632/aging.103059
How to Cite
Copyright © 2020 Hu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.