Ethanol extract of Elephantopus scaber Linn. Attenuates inflammatory response via the inhibition of NF-κB signaling by dampening p65-DNA binding activity in lipopolysaccharide-activated macrophages

J Ethnopharmacol. 2020 Mar 25:250:112499. doi: 10.1016/j.jep.2019.112499. Epub 2019 Dec 23.

Abstract

Ethnopharmacological relevance: Elephantopus scaber Linn. (E.scaber) is a widely-used traditional herb whose use has been documented for various inflammatory diseases such as fever, sore throat, dysentery, carbuncle and so on. However, the effect and mechanism of E.scaber in LPS-activated macrophages remain unclear.

Aim: This study aims to investigate the anti-inflammatory mechanism of the ethanol extract of E.scaber (ESE) in lipopolysaccharide (LPS)-induced inflammatory models.

Materials and methods: Griess reagent was used to determine NO production, and the levels of TNF-α, IL-6, MCP-1 and IL-1β were determined by ELISA kits. The molecular mechanism research was performed by RT-PCR, Western blot, and electrophoretic mobility shift assay (EMSA). LPS-induced endotoxemia mouse model was used for evaluating the in vivo anti-inflammatory action of ESE.

Results: ESE suppressed LPS-induced iNOS, TNF-α, IL-6, MCP-1 and IL-1β transcription as well as supernatant NO, TNF-α, IL-6, MCP-1 and IL-1β production in macrophages. Although ESE inhibited NF-κB activation, it did not affect the IκBα phosphorylation and degradation and the NF-κB p65 nuclear translocation. The result of EMSA revealed that ESE inhibited the NF-κB p65-DNA binding activity. Additionally, ESE also decreased the proinflammatory cytokines in serum and peritoneal lavage fluid of LPS-induced endotoxemic mice.

Conclusion: ESE has a potently anti-inflammatory effect through inhibiting the NF-κB p65-DNA binding activity in LPS-activated macrophages.

Keywords: DNA binding; Elephantopus scaber Linn.; Inflammation; Macrophage; NF-κB; Proinflammatory mediators.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / isolation & purification
  • Anti-Inflammatory Agents / pharmacology*
  • Asteraceae / chemistry*
  • Cytokines / metabolism
  • DNA / metabolism
  • Inflammation / drug therapy*
  • Inflammation / pathology
  • Inflammation Mediators / metabolism
  • Lipopolysaccharides
  • Macrophages / drug effects
  • Macrophages / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred ICR
  • NF-kappa B / metabolism
  • Plant Extracts / pharmacology*
  • RAW 264.7 Cells
  • Transcription Factor RelA / metabolism

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Inflammation Mediators
  • Lipopolysaccharides
  • NF-kappa B
  • Plant Extracts
  • Transcription Factor RelA
  • DNA