Andrographolide derivative Andro-III modulates neuroinflammation and attenuates neuropathological changes of Alzheimer's disease via GSK-3ß/NF-κB/CREB pathway.
Eur J Pharmacol
; 965: 176305, 2024 Feb 15.
Article
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| MEDLINE
| ID: mdl-38160932
ABSTRACT
Andrographolide has anti-inflammatory and neuroprotective effects, making it a potential therapeutic option for Alzheimer's disease (AD). Our research group optimized its structure in a previous study to minimize the risk of renal toxicity, which would beneficial for future clinical research. This study aims to examine the impact of Andro-III on enhancing cognitive learning ability in 3xTg-AD mice, as well as the mechanisms involved. Andro-III improved spatial learning ability, prevented the loss of Nysted's vesicles, reduced the accumulation of ß-amyloid (Aß) and tau proteins, and suppressed microglial activation. Further research found that the expression of nuclear factor kappa-B RelA (NF-κB p65) expression and glycogen synthase kinase-3ß (GSK-3ß) activity were inhibited, while CREB was upregulated in brain tissue treated with Andro-III. Moreover, Andro-III downregulated the expression of IBA1 and inflammatory factors in microglial cells of mice induced by Aß. The regulation of the GSK-3ß/NF-κB/CREB pathway was similar to that observed in 3xTg-AD mice. Therefore, Andro-III modulates neuroinflammation and attenuates neuropathological changes of AD via the GSK-3ß/NF-κB/CREB pathway.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Diterpenos
/
Enfermedad de Alzheimer
Límite:
Animals
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En
Revista:
Eur J Pharmacol
Año:
2024
Tipo del documento:
Article