Objective: Diets rich in quercitrin show a neuroprotective effect, but the mechanism is not very clear at present. The objective of this study is to explore the effect and mechanism of quercitrin in the treatment of alzheimer’s disease (AD). Methods: 5XFAD transgenic mice were fed with a diet supplemented with quercitrin for three consecutive months. Behavioral experiments were conducted to assess the cognitive ability, luminex liquid chip technology was used to assess the production of proinflammatory cytokines and immunohistochemistry was used to elucidate the activation of microglia. Results: Quercitrin increased the frequency in exploring new objects, shortened the escape latency and increased the frequency crossing the platform in AD model mice. Quercitrin inhibited the activation and proliferation of microglia, inhibited the secretion of inflammatory cytokines and chemokines and reduced the accumulation of amyloid-β plaques in AD model mice. Conclusion: Quercitrin improved mice cognitive impairment through alleviating the intensity of inflammatory response and is a promising medicinal plant extract in the treatment of AD.

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 anti-inflammatory 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-κB 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 Aβ plaques. AS-IV cut down the mRNA expression of IL-1β, COX-2, iNOS and TNF-α in LPS-stimulated BV-2 cells by suppressing the phosphorylation of IκB 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.

Inflammatory reaction in the brain activates glial cells, and over-activated glial cells secrete inflammatory mediators, which aggravates the inflammatory response in the brain and accelerates the development of Alzheimer's disease (AD) in turn. Numerous natural compounds from herbs can alleviate inflammation, and it is very promising to find anti-neuroinflammatory natural compounds. Micheliolide (MCL) is an asesquiterpene lactone. Studies have proved that MCL showed an obvious anti-inflammatory property. Nevertheless, whether MCL can treat AD has not been determined. In this research, AD model mice were fed with a diet supplemented MCL for 3 months, the cognitive ability and inflammatory state of mice were detected. We found that MCL raised the frequency of touching novel objects, cut down the escape latency, raised the number of crossing platform, inhibited the infiltration of inflammatory cells and the secretion of interleukin-1α (IL-1α), IL-12p40, IL-13, IL-17A, tumor necrosis factor-α (TNF-α), granulocyte colony stimulating factor (G-CSF), macrophage inflammatory protein-1α (MIP-1α) and monocyte chemotactic protein-1 (MCP-1) in peripheral blood samples, inhibited the hyperplasia of glial cells and the production of IL-1α, IL-4, G-CSF, granulocyte-macrophage colony stimulating factor (GM-CSF), MIP-1α and MIP-1β, and reduced the deposition of Aβ peptides in the brain of AD mice. We also concluded that MCL dropped the expression of IL-1β, TNF-α, cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and the phosphorylation of IκB, p65 and Akt in BV-2 cells. In conclusion, MCL alleviates the intensity of systemic inflammatory reaction via inhibiting nuclear transcription factor κ gene binding (NF-κB) and phosphoinositide-3-kinase/serine/threonine kinase (PI3K/Akt) pathways in glial cells, and improves the cognitive impairment of AD mice. Therefore, MCL could be a therapeutic candidate for AD.