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Cornuside ameliorates cognitive impairments via RAGE/TXNIP/NF-κB signaling in Aβ 1-42 induced Alzheimer's disease mice.
- Source :
-
Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology [J Neuroimmune Pharmacol] 2024 May 23; Vol. 19 (1), pp. 24. Date of Electronic Publication: 2024 May 23. - Publication Year :
- 2024
-
Abstract
- Cornuside has been discovered to improve learning and memory in AD mice, however, its underlying mechanism was not fully understood. In the present study, we established an AD mice model by intracerebroventricular injection of Aβ <subscript>1-42</subscript> , which were treated with cornuside (3, 10, 30 mg/kg) for 2 weeks. Cornuside significantly ameliorated cognitive function of AD mice in series of behavioral tests, including Morris water maze test, nest building test, novel object recognition test and step-down test. Additionally, cornuside could attenuate neuronal injury, and promote cholinergic synaptic transmission by restoring the level of acetylcholine (ACh) via inhibiting acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), as well as facilitating choline acetyltransferase (ChAT). Furthermore, cornuside inhibited oxidative stress levels amplified as decreased malondialdehyde (MDA), by inhibiting TXNIP expression, improving total anti-oxidative capacity (TAOC), raising activities of superoxide dismutase (SOD) and catalase (CAT). Cornuside also reduced the activation of microglia and astrocytes, decreased the level of proinflammatory factors TNF-α, IL-6, IL-1β, iNOS and COX2 via interfering RAGE-mediated IKK-IκB-NF-κB phosphorylation. Similar anti-oxidative and anti-inflammatory effects were also found in LPS-stimulated BV2 cells via hampering RAGE-mediated TXNIP activation and NF-κB nuclear translocation. Virtual docking revealed that cornuside could interact with the active pocket of RAGE V domain directly. In conclusion, cornuside could bind to the RAGE directly impeding the interaction of Aβ and RAGE, and cut down the expression of TXNIP inhibiting ROS production and oxidative stress, as well as hamper NF-κB p65 mediated the inflammation.<br /> (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
- Subjects :
- Animals
Mice
Male
Oxidative Stress drug effects
Alzheimer Disease drug therapy
Alzheimer Disease metabolism
Alzheimer Disease chemically induced
Amyloid beta-Peptides toxicity
Amyloid beta-Peptides metabolism
Peptide Fragments toxicity
Cognitive Dysfunction drug therapy
Cognitive Dysfunction metabolism
Cognitive Dysfunction chemically induced
Signal Transduction drug effects
Receptor for Advanced Glycation End Products metabolism
NF-kappa B metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1557-1904
- Volume :
- 19
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 38780885
- Full Text :
- https://doi.org/10.1007/s11481-024-10120-2