Andrographolide derivative Andro-III modulates neuroinflammation and attenuates neuropathological changes of Alzheimer's disease via GSK-3β/NF-κB/CREB pathway.

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 β-amyloid (Aβ) 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-3β (GSK-3β) 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 Aβ. The regulation of the GSK-3β/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-3β/NF-κB/CREB pathway.
Competing Interests: Declaration of competing interest The manuscript ‘Andrographolide derivative Andro-III can attenuates neuroinflammation via through GSK-3β/NF-κB/CREB pathway in both in vivo and vitro models of Alzheimer's disease’ has not been published before and is not being considered for publication elsewhere. All authors have contributed to the creation of this manuscript for important intellectual content and read and approved the final manuscript. We declare there is no conflict of interest.
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