Ampelopsin attenuates lipopolysaccharide-induced inflammatory response through the inhibition of the NF-κB and JAK2/STAT3 signaling pathways in microglia

Int Immunopharmacol. 2017 Mar:44:1-8. doi: 10.1016/j.intimp.2016.12.018. Epub 2016 Dec 18.

Abstract

Increasing evidence suggests that microglia are a major cellular contributor to neuroinflammation. The present study investigated whether Ampelopsin (Amp), a type of flavanonol derivative from Ampelopsis grossedentata, may exert an anti-inflammatory effect on lipopolysaccharide (LPS)-induced BV2 and primary microglia cells. We found that pre-treatment of microglia cells with Amp before LPS with a non-cytotoxic concentration range decreased the production of nitric oxide (NO) and prostaglandin E2 (PGE2). Amp also suppressed the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) at the mRNA and protein levels. In addition, LPS-induced production of pro-inflammatory cytokines such as interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) was obviously reduced by Amp. Our mechanistic study indicated that Amp suppressed LPS-induced activation of the IκB/NF-κB inflammation pathway without affecting changes in the phosphorylation levels of mitogen-activated protein kinases (MAPKs) in BV2 cells. Further studies revealed that Amp markedly reduced the phosphorylation levels of JAK2-STAT3 and STAT3 nuclear translocation. Overall, our data suggest that Amp can suppress the LPS-induced inflammatory response of microglial cells, indicating that Amp has potential for the treatment of inflammation-mediated neurodegenerative diseases.

Keywords: Ampelopsin·microglia·neuroinflammation·lipopolysaccharide·NF-κB·JAK2/STAT3.

MeSH terms

  • Ampelopsis / immunology*
  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Cells, Cultured
  • Cytokines / metabolism
  • Dinoprostone / metabolism
  • Flavonoids / pharmacology*
  • Humans
  • Inflammation Mediators / metabolism
  • Janus Kinase 2 / metabolism*
  • Lipopolysaccharides / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Microglia / drug effects*
  • Microglia / immunology
  • NF-kappa B / metabolism*
  • Neurogenic Inflammation / drug therapy*
  • Neurogenic Inflammation / immunology
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type II / metabolism
  • STAT3 Transcription Factor / metabolism*
  • Signal Transduction / drug effects

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Flavonoids
  • Inflammation Mediators
  • Lipopolysaccharides
  • NF-kappa B
  • STAT3 Transcription Factor
  • Stat3 protein, mouse
  • ampelopsin
  • Nitric Oxide
  • Nitric Oxide Synthase Type II
  • Jak2 protein, mouse
  • Janus Kinase 2
  • Dinoprostone