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Inhibiting the NLRP3 Inflammasome Activation with MCC950 Ameliorates Diabetic Encephalopathy in db/db Mice

by 1,2,3,4, 1,2,3,4, 1,2,3,4, 1,2,3,4, 1,2,3,4,* and 1,2,3,4,*
1
Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100193, China
2
Key Laboratory of Bioactive Substances and Resource Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing 100193, China
3
Key Laboratory of Efficacy Evaluation of Chinese Medicine against Glycolipid Metabolic Disorders, State Administration of Traditional Chinese Medicine, Beijing 100193, China
4
Zhongguancun Open Laboratory of the Research and Development of Natural Medicine and Health Products, Beijing 100193, China
*
Authors to whom correspondence should be addressed.
Molecules 2018, 23(3), 522; https://doi.org/10.3390/molecules23030522
Received: 9 January 2018 / Revised: 3 February 2018 / Accepted: 5 February 2018 / Published: 27 February 2018
Diabetes is associated with a high risk of developing cognitive dysfunction and neuropsychiatric disabilities, and these disease symptomsare termed diabetic encephalopathy (DEP). Inflammation is involved in the development of DEP. The cleavage and maturation of the proinflammatory cytokine interleukin (IL)-1β is regulated by the NLRP3 inflammasome. Obese and type 2 diabetic db/db mice show anxiety- and depression-like behaviors and cognitive disorders associated with hippocampal inflammation. The purpose of this study was to explore the role of NLRP3 inflammasome in DEP. Results showed that expression levels of inflammasome components including NLRP3, apoptosis-associated speck-like protein (ASC), and caspase-1, as well as IL-1β in the hippocampus of diabetic db/db mice were higher than those of non-diabetic db/m mice. Treatment of db/db mice with NLRP3 inflammasome inhibitor MCC950 ameliorated anxiety- and depression-like behaviors as well as cognitive dysfunction, and reversed increased NLRP3, ASC, and IL-1βexpression levels and caspase-1 activity in hippocampus. Moreover, MCC950 treatment significantly improved insulin sensitivity in db/db mice. These results demonstrate that inhibition of NLRP3 inflammasome activation may prove to be a potential therapeutic approach for DEP treatment. View Full-Text
Keywords: diabetic encephalopathy; NLRP3 inflammasome; MCC950; interleukin-1β diabetic encephalopathy; NLRP3 inflammasome; MCC950; interleukin-1β
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MDPI and ACS Style

Zhai, Y.; Meng, X.; Ye, T.; Xie, W.; Sun, G.; Sun, X. Inhibiting the NLRP3 Inflammasome Activation with MCC950 Ameliorates Diabetic Encephalopathy in db/db Mice. Molecules 2018, 23, 522. https://doi.org/10.3390/molecules23030522

AMA Style

Zhai Y, Meng X, Ye T, Xie W, Sun G, Sun X. Inhibiting the NLRP3 Inflammasome Activation with MCC950 Ameliorates Diabetic Encephalopathy in db/db Mice. Molecules. 2018; 23(3):522. https://doi.org/10.3390/molecules23030522

Chicago/Turabian Style

Zhai, Yadong, Xiangbao Meng, Tianyuan Ye, Weijie Xie, Guibo Sun, and Xiaobo Sun. 2018. "Inhibiting the NLRP3 Inflammasome Activation with MCC950 Ameliorates Diabetic Encephalopathy in db/db Mice" Molecules 23, no. 3: 522. https://doi.org/10.3390/molecules23030522

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