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Quercetin protects against diabetic encephalopathy via SIRT1/NLRP3 pathway in db/db mice
Authors:Tian Hu  Xin-Yi Lu  Jing-Jing Shi  Xiao-Qi Liu  Qu-Bo Chen  Qi Wang  Yun-Bo Chen  Shi-Jie Zhang
Institution:1. Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, China

Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou, China;2. Biological Resource Center, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China;3. Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, China;4. Department of Neurology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China

Abstract:Epidemiological studies have found that diabetes and cognitive dysfunction are closely related. Quercetin has been certified with the effect on improving diabetes mellitus (DM) and cognitive impairment. However, the effect and related mechanism of quercetin on diabetic encephalopathy (DE) are still ambiguous. In this study, we used the db/db mice (diabetic model) to discover whether quercetin could improve DE through the Sirtuin1/NLRP3 (NOD-, LRR- and pyrin domain-containing 3) pathway. Behavioural results (Morris water maze and new object recognition tests) showed that quercetin (70 mg/kg) improved the learning and memory. Furthermore, quercetin alleviated insulin resistance and the level of fasting blood glucose. Besides, Western blot analysis also showed that quercetin increased the protein expressions of nerve- and synapse-related protein, including postsynapticdensity 93 (PSD93), postsynapticdensity 95 (PSD95), brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in the brain of db/db mice. Quercetin also increased the protein expression of SIRT1 and decreased the expression of NLRP3 inflammation-related proteins, including NLRP3, the adaptor protein ASC and cleaved Caspase-1, the pro-inflammatory cytokines IL-1β and IL-18. In conclusion, the present results indicate that the SIRT1/NLRP3 pathway may be a crucial mechanism for the neuroprotective effect of quercetin against DE.
Keywords:diabetic encephalopathy  NLRP3 inflammasome  quercetin  SIRT1
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