1. Academic Validation
  2. Inhibiting the NLRP3 Inflammasome Activation with MCC950 Ameliorates Diabetic Encephalopathy in db/db Mice

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

  • Molecules. 2018 Feb 27;23(3):522. doi: 10.3390/molecules23030522.
Yadong Zhai 1 2 3 4 Xiangbao Meng 5 6 7 8 Tianyuan Ye 9 10 11 12 Weijie Xie 13 14 15 16 Guibo Sun 17 18 19 20 Xiaobo Sun 21 22 23 24
Affiliations

Affiliations

  • 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. [email protected].
  • 2 Key Laboratory of Bioactive Substances and Resource Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing 100193, China. [email protected].
  • 3 Key Laboratory of Efficacy Evaluation of Chinese Medicine against Glycolipid Metabolic Disorders, State Administration of Traditional Chinese Medicine, Beijing 100193, China. [email protected].
  • 4 Zhongguancun Open Laboratory of the Research and Development of Natural Medicine and Health Products, Beijing 100193, China. [email protected].
  • 5 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. [email protected].
  • 6 Key Laboratory of Bioactive Substances and Resource Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing 100193, China. [email protected].
  • 7 Key Laboratory of Efficacy Evaluation of Chinese Medicine against Glycolipid Metabolic Disorders, State Administration of Traditional Chinese Medicine, Beijing 100193, China. [email protected].
  • 8 Zhongguancun Open Laboratory of the Research and Development of Natural Medicine and Health Products, Beijing 100193, China. [email protected].
  • 9 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. [email protected].
  • 10 Key Laboratory of Bioactive Substances and Resource Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing 100193, China. [email protected].
  • 11 Key Laboratory of Efficacy Evaluation of Chinese Medicine against Glycolipid Metabolic Disorders, State Administration of Traditional Chinese Medicine, Beijing 100193, China. [email protected].
  • 12 Zhongguancun Open Laboratory of the Research and Development of Natural Medicine and Health Products, Beijing 100193, China. [email protected].
  • 13 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. [email protected].
  • 14 Key Laboratory of Bioactive Substances and Resource Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing 100193, China. [email protected].
  • 15 Key Laboratory of Efficacy Evaluation of Chinese Medicine against Glycolipid Metabolic Disorders, State Administration of Traditional Chinese Medicine, Beijing 100193, China. [email protected].
  • 16 Zhongguancun Open Laboratory of the Research and Development of Natural Medicine and Health Products, Beijing 100193, China. [email protected].
  • 17 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. [email protected].
  • 18 Key Laboratory of Bioactive Substances and Resource Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing 100193, China. [email protected].
  • 19 Key Laboratory of Efficacy Evaluation of Chinese Medicine against Glycolipid Metabolic Disorders, State Administration of Traditional Chinese Medicine, Beijing 100193, China. [email protected].
  • 20 Zhongguancun Open Laboratory of the Research and Development of Natural Medicine and Health Products, Beijing 100193, China. [email protected].
  • 21 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. [email protected].
  • 22 Key Laboratory of Bioactive Substances and Resource Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing 100193, China. [email protected].
  • 23 Key Laboratory of Efficacy Evaluation of Chinese Medicine against Glycolipid Metabolic Disorders, State Administration of Traditional Chinese Medicine, Beijing 100193, China. [email protected].
  • 24 Zhongguancun Open Laboratory of the Research and Development of Natural Medicine and Health Products, Beijing 100193, China. [email protected].
Abstract

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.

Keywords

MCC950; NLRP3 inflammasome; diabetic encephalopathy; interleukin-1β.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-12815A
    99.61%, NLRP3 Inhibitor