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Neferine alleviates memory and cognitive dysfunction in diabetic mice through modulation of the NLRP3 inflammasome pathway and alleviation of endoplasmic-reticulum stress.
- Source :
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International immunopharmacology [Int Immunopharmacol] 2020 Jul; Vol. 84, pp. 106559. Date of Electronic Publication: 2020 May 08. - Publication Year :
- 2020
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Abstract
- Accumulating clinical and epidemiological evidence indicates a close relationship between diabetes mellitus and dysfunction in memory and cognition. Neferine (NE) is a unique bis-benzylisoquinoline alkaloid derived from the seed embryo of Nelumbo nucifera (Lotus), an herbal medicine with a long history of use in used in China. NE has been reported to ameliorate diabetes mellitus and exert considerable protective effects on the central nervous system. Thus, this study aimed to investigate the effects of NE on memory and cognitive dysfunction in db/db mouse model of diabetes. First, we found that NE treatments significantly ameliorated behavioral impairment and cognitive dysfunction in the Morris water maze, Y-maze, and fear conditioning test in db/db mice. Additionally, in these diabetic mice, NE decreased fasting glucose and insulin resistance while promoting lipid metabolism. Furthermore, NE treatments alleviated oxidative stress and inhibited inflammatory responses in the hippocampus. Further investigations showed that NE suppressed the NOD-like receptor protein 3 (NLRP3) inflammasome pathway via down-regulating the levels of thioredoxin-interacting protein (TXNIP), NLRP3 inflammasomes, apoptosis-associated speck-like protein containing a CARD (ASC), and mature interleukin-1β (IL-1β) in the hippocampus. Moreover, NE alleviated endoplasmic-reticulum (ER) stress via down-regulating the levels of immunoglobulin heavy-chain-binding protein (GRP78), C/EBP homologous protein (CHOP), proteins kinase R-like endoplasmic reticulum kinase (PERK), inositol-requiring enzyme 1 (IRE1), and activating transcription factor 6 (ATF6) in the hippocampus. In conclusion, these results suggest that NE ameliorated memory and cognitive dysfunction, possibly through modulating the NLRP3 inflammasome pathways and alleviating ER stress.<br />Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest regarding the publication of this paper.<br /> (Copyright © 2020 Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Benzylisoquinolines pharmacology
Cognitive Dysfunction metabolism
Cytokines metabolism
Diabetes Mellitus, Experimental metabolism
Endoplasmic Reticulum Chaperone BiP
Endoplasmic Reticulum Stress drug effects
Female
Hippocampus drug effects
Hippocampus metabolism
Inflammasomes metabolism
Lipid Metabolism drug effects
Memory drug effects
Memory Disorders metabolism
Mice
NLR Family, Pyrin Domain-Containing 3 Protein metabolism
Neuroprotective Agents pharmacology
Spatial Learning drug effects
Benzylisoquinolines therapeutic use
Cognitive Dysfunction drug therapy
Diabetes Mellitus, Experimental drug therapy
Memory Disorders drug therapy
Neuroprotective Agents therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1878-1705
- Volume :
- 84
- Database :
- MEDLINE
- Journal :
- International immunopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 32402951
- Full Text :
- https://doi.org/10.1016/j.intimp.2020.106559