Andrographolide ameliorates neuroinflammation in APP/PS1 transgenic mice

Int Immunopharmacol. 2021 Jul:96:107808. doi: 10.1016/j.intimp.2021.107808. Epub 2021 May 30.

Abstract

Alzheimer's disease is a devastating neurodegenerative disorder, with no disease-modifying treatment available yet. There is increasing evidence that neuroinflammation plays a critical role in the pathogenesis of AD. Andrographolide (Andro), a labdane diterpene extracted from the herb Andrographis paniculata, has been reported to exhibit neuroprotective property in central nervous system diseases. However, its effects on Aβ and Aβ-induced neuroinflammation have not yet been studied. In the present study, we found that Andro administration significantly alleviated cognitive impairments, reduced amyloid-β deposition, inhibited microglial activation, and decreased the secretion of proinflammatory factors in APP/PS1 mice. Furthermore, transcriptome sequencing analysis revealed that Andro could significantly decrease the expression of Itgax, TLR2, CD14, CCL3, CCL4, TLR1, and C3ar1 in APP/PS1 mice, which was further validated by qRT-PCR. Our results suggest that Andro might be a potential therapeutic drug for AD by regulating neuroinflammation.

Keywords: APP/PS1; Alzheimer’s disease; Andrographolide; Neuroinflammation; RNA-seq.

MeSH terms

  • Amyloid beta-Peptides / metabolism
  • Amyloid beta-Protein Precursor / genetics
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Behavior, Animal / drug effects
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism
  • Cognitive Dysfunction / drug therapy*
  • Cognitive Dysfunction / genetics
  • Cognitive Dysfunction / metabolism
  • Diterpenes / pharmacology
  • Diterpenes / therapeutic use*
  • Encephalitis / drug therapy*
  • Encephalitis / genetics
  • Encephalitis / metabolism
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Male
  • Mice, Transgenic
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use*
  • Presenilin-1 / genetics
  • Transcriptome / drug effects

Substances

  • APP protein, mouse
  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor
  • Anti-Inflammatory Agents
  • Diterpenes
  • Neuroprotective Agents
  • Presenilin-1
  • presenilin 1, mouse
  • andrographolide