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-1 beta and IL-6. In the present study, we generated the rat model of AD by injecting A beta(1-42) 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 A beta(1-42) induction. NLD also attenuated activation of microglia and astrocytes induced by A beta(1-2.) Subsequently, NLD dose-dependently reduced levels TNF-alpha, IL-1 beta and IL-6 by inhibiting the NF-B-K 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.