Angelicae Gigantis Radix Regulates LPS-Induced Neuroinflammation in BV2 Microglia by Inhibiting NF-κB and MAPK Activity and Inducing Nrf-2 Activity

Molecules. 2019 Oct 18;24(20):3755. doi: 10.3390/molecules24203755.

Abstract

Angelicae Gigantis Radix (AGR) has been widely used as a traditional medicine in East Asia. The effects of AGR on neuroinflammation have not previously been studied in detail. In the study presented here, we investigated the antineuroinflammatory properties of this herb and its mechanism of operation. The effects of AGR on neuroinflammation were studied by measuring the production of inflammatory factors and related enzymes, and analyzing the expression levels of proteins and genes involved its activity, in lipopolysaccharide (LPS)-stimulated BV2 microglia. We found that AGR pretreatment strongly inhibits the production of nitric oxide (NO), cytokines, and the enzymes inducible nitric oxide synthase (iNOS), and cyclooxygenase (COX)-2, and effectively induces the activation of heme oxygenase (HO)-1 and its regulator, nuclear factor erythroid 2-related factor 2 (Nrf-2). We also found that AGR effectively regulates the activation of nuclear factor (NF)-κB and mitogen-activated protein kinase (MAPK). We confirmed the antineuroinflammatory effects of the main constituents of the plant as identified by high-performance liquid chromatography (HPLC). Our results indicate that the neuroinflammation inhibitory activity of AGR occurs through inhibition of NF-κB and MAPK and activation of Nrf-2.

Keywords: Angelicae Gigantis Radix; MAPK; NF-κB; Nrf-2; antineuroinflammation.

MeSH terms

  • Angelica / chemistry*
  • Animals
  • Cell Line
  • Cell Survival / drug effects
  • Chromatography, High Pressure Liquid
  • Ethanol / chemistry
  • Ethanol / pharmacology*
  • Gene Expression Regulation / drug effects
  • Lipopolysaccharides / adverse effects*
  • Medicine, East Asian Traditional
  • Mice
  • Microglia / cytology*
  • Microglia / drug effects
  • Microglia / metabolism
  • Mitogen-Activated Protein Kinases / metabolism
  • NF-E2-Related Factor 2 / metabolism*
  • NF-kappa B / metabolism
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology
  • Plant Roots / chemistry
  • Signal Transduction

Substances

  • Lipopolysaccharides
  • NF-E2-Related Factor 2
  • NF-kappa B
  • Nfe2l2 protein, mouse
  • Plant Extracts
  • Ethanol
  • Mitogen-Activated Protein Kinases