Abstract

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.

Highlights

  • Alzheimer’s disease (AD) is an irreversible neurodegenerative disease that is clinically characterized as a cognitive disorder and is the leading cause of dementia in the elderly [1]

  • Naoling decoction (NLD)-M that had no significant difference in pIκBα and cytoplasmic/nuclear p65 expression compared to the NLD-L group showed stronger reduction in ASC and caspase-1 p20 than NLD-L (p < 0.05; Figure 7D, 7E). These results suggested that NLD treatment inhibited the activated NF-κB signaling pathway and formation of ASCdependent inflammasome in the hippocampus in a dosedependent manner. This is the first study in our knowledge to have investigated the effects of traditional Chinese medicine (TCM) treatment on neuroinflammatory network in the AD brain

  • Our study in the AD rat model demonstrates that NLD has significant benefits

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Summary

Introduction

Alzheimer’s disease (AD) is an irreversible neurodegenerative disease that is clinically characterized as a cognitive disorder and is the leading cause of dementia in the elderly [1]. It is one of the big healthcare challenges of the 21st century with more than 40 million people affected worldwide and its incidence is expected to substantially increase [2]. By 2050, the AD patient cohort is expected to be 115 million, costing approximately €1.6 trillion per year [3] Inspite of this grave situation, no effective treatments are available for AD [1] and there is an urgent need for novel effective AD therapeutics [4]. Suppression of the neuroinflammation is a major therapeutic target for AD

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