Naoling decoction restores cognitive function by inhibiting the neuroinflammatory network in a rat model of Alzheimer's disease.

Neuroinflammation is central to the pathogenesis of Alzheimer's disease (AD). We previously showed that Naoling decoction (NLD), a traditional Chinese medicine, was effective against AD, acting by inhibiting expression of IL-1β and IL-6. In the present study, we generated the rat model of AD by injecting Aβ1-42 peptide intracerebroventricularly and evaluated the dose-dependent effects of NLD treatment. The NLD-treated rats exhibited significant improvements in cognitive function as evaluated by the Morris water maze test. Golgi-Cox staining revealed that NLD treatment dose-dependently increased dendritic spines in the CA1 region, which were diminished in vehicle-treated rats. Further, NLD treatment normalized hippocampal Chromogranin A levels, which were elevated by Aβ1-42 induction. NLD also attenuated activation of microglia and astrocytes induced by Aβ1-42. Subsequently, NLD dose-dependently reduced levels TNF-α, IL-1β and IL-6 by inhibiting the NF-κB signaling pathway and the ASC-dependent inflammasome in the hippocampus. These findings reveal that NLD is a promising therapeutic agent that exerts inhibitory effects at multiple sites within the neuroinflammatory network induced in AD.