Alpinae Oxyphyllae Fructus alleviated LPS-induced cognitive impairments via PI3K/AKT/NF-κB signaling pathway

Environ Toxicol. 2022 Mar;37(3):489-503. doi: 10.1002/tox.23415. Epub 2021 Dec 7.

Abstract

Herein, we aim to investigate the effect of Alpinae Oxyphyllae Fructus (AOF) on cognitive impairments and neuroinflammation in a lipopolysaccharide (LPS)-induced models of AD. Mice were injected intracerebroventricularly with LPS, and then administrated AOF using a gavage for 6 weeks. Spatial working memory was assessed using the Y-maze and Morris water maze test, whereas the levels of PI3K, AKT, p-AKT, p-GSK3β, GSK3β, NF-κB, IL-1β, IL-6, and TNF-α were evaluated using western blot and ELISA assay. Our data showed that AOF was able to significantly alleviate the memory decline in LPS-induced AD mice. Moreover, AOF was able to protect neurons through the PI3K/AKT signaling pathway and significantly decrease NF-κB, IL-6, IL-1β, and TNF-α levels in the hippocampal and cortex tissues, which were reversed through the use of LY294002. Additionally, we discovered that AOF could significantly decrease the high expression of cytokines as well as the expression and translocation of NF-κB induced by LPS in PC12 cells. These results demonstrate the anti-neuroinflammatory effect of AOF in both cell and animal models of AD, thereby slowing down the process and development of the disease.

Keywords: Alpinae Oxyphyllae Fructus; Alzheimer's disease; LPS; PI3K/AKT/NF-κB; inflammatory cytokines.

MeSH terms

  • Animals
  • Cognitive Dysfunction* / chemically induced
  • Lipopolysaccharides* / toxicity
  • Mice
  • NF-kappa B / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rats
  • Signal Transduction

Substances

  • Lipopolysaccharides
  • NF-kappa B
  • Proto-Oncogene Proteins c-akt