Astragaloside IV attenuates neuroinflammation and ameliorates cognitive impairment in Alzheimer's disease via inhibiting NF-κB signaling pathway

The inflammatory process plays a significant role in the pathophysiology of Alzheimer's disease (AD). Anti-neuroinflammatory cascade is now considered an important measure for AD treatment. Astragaloside IV (AS-IV), a saponin of Astragali radix, has shown significant antiinflammatory properties and protective effects against neurodegenerative diseases. However, the mechanisms of AS-IV in treating Alzheimer's disease (AD) have not been fully determined. The experiment research was carried out to comprehensively confirm the beneficial effects and underlying molecular mechanisms of AS-IV to AD. In this research, BV-2 cells were cultured in vitro and treated by AS-IV under the stimulation of LPS, qRT-PCR was adopted to analyze the mRNA expression level of inflammatory factors. Western-blot was carried out to analyze the phosphorylation level of NF-kappa B signaling pathway. 5xFAD mice were administrated AS-IV mixed in the diet for 3 months. Behavioral experiments were adopted to analyze learning and memory abilities. Immunohistochemical staining was adopted to observe the proliferation of microglias and the accumulation of A beta plaques. AS-IV cut down the mRNA expression of IL-1 beta, COX-2, iNOS and TNF- alpha in LPS-stimulated BV-2 cells by suppressing the phosphorylation of I.B and p65, and inhibited the phosphorylated p65 from entering the nucleus. AS-IV increased the frequency of recognizing new objects in the novel object recognition test, shortened the escape latency, raised the number of crossing platform in the Morris water maze, inhibited the hyperplasia of microglias, and reduced the production of senile plaques in 5xFAD mice. In brief, AS-IV ameliorates learning and memory impairment by relieving the intensity of neuroinflammatory response in AD. Therefore, AS-IV is very promising to be a herbal medicine for AD treatment.