Artemisiae Iwayomogii Herba inhibits lipopolysaccharide-induced neuroinflammation by regulating NF-κB and MAPK signaling pathways

Phytomedicine. 2021 Apr:84:153501. doi: 10.1016/j.phymed.2021.153501. Epub 2021 Feb 10.

Abstract

Background: Neuroinflammation plays a major role in the development of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. The regulation of microglia is an efficient therapeutic approach to controlling neuroinflammation.

Purpose: In this study, we aimed to determine whether Artemisiae Iwayomogii Herba (AIH), which is herbal medicine traditionally used for inflammation-related disorders, controls neuroinflammatory responses by regulating the microglia-mediated signaling pathway.

Methods: BV-2 microglial cells were treated with AIH and lipopolysaccharides (LPS), then various pro-inflammatory mediators were analyzed using griess reaction, quantitative reverse-transcription polymerase chain reaction, or western blotting. C57BL/6 J mice were orally administered by AIH for 17 days and intraperitoneally injected with LPS for the last 14 days. The brains were collected and the microglial activation and nucleotide-binding oligomerization domain-, leucine-rich repeat-, and pyrin domain-containing 3 (NLRP3) expression in the cortex and hippocampus were analyzed using immunohistochemistry or western blotting.

Results: In BV-2 microglial cells, we found that AIH inhibited nitric oxide (NO) production induced by LPS. AIH also suppressed the expressions of pro-inflammatory mediators, including inducible NO synthase, cyclooxygenase-2, tumor necrosis factor-α, and interleukin-6. The study also revealed that the effects of AIH are related to the regulation of the nuclear factor kappa B (NF-κB) and the mitogen-activated protein kinase (MAPK) signaling pathway. Additionally, we found that AIH prevented the formation of NLRP3 inflammasomes. Consistent with the results of in vitro studies on the brains of LPS-injected mice, we observed that AIH suppressed microglial activation and NLRP3 expression.

Conclusion: Taken together, these results suggest that AIH attenuates neuroinflammation by regulating the NF-κB and MAPK pathways, and it may be used for treating neurological diseases.

Keywords: Artemisia iwayomogi; Mitogen-activated protein kinases; NLRP3; Neuroinflammation; Nuclear factor kappa B.

MeSH terms

  • Animals
  • Artemisia / chemistry
  • Cell Line
  • Cyclooxygenase 2 / metabolism
  • Inflammation / chemically induced
  • Inflammation / drug therapy*
  • Inflammation / metabolism
  • Inflammation Mediators / metabolism
  • Lipopolysaccharides / toxicity
  • MAP Kinase Signaling System / drug effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microglia / drug effects*
  • Microglia / metabolism
  • Microglia / pathology
  • NF-kappa B / metabolism*
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type II / metabolism
  • Plant Preparations / chemistry
  • Plant Preparations / pharmacology*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Inflammation Mediators
  • Lipopolysaccharides
  • NF-kappa B
  • Plant Preparations
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2