Forsythoside A protects against lipopolysaccharide-induced acute lung injury through up-regulating microRNA-124

Clin Sci (Lond). 2020 Oct 16;134(19):2549-2563. doi: 10.1042/CS20200598.

Abstract

Acute lung injury (ALI) is a life-threatening disease without effective pharmacotherapies, so far. Forsythia suspensa is frequently used in the treatment of lung infection in traditional Chinese medicine. In search for natural anti-inflammatory components, the activity and the underlying mechanism of Forsythoside A (FA) from Forsythia suspensa were explored. In the present paper, BALB/c mice and murine RAW 264.7 cells were stimulated by LPS to establish inflammation models. Data showed that FA inhibited the production of TNF-α and IL-6 and the activation of STAT3 in LPS-stimulated RAW 264.7 cells. Additionally, FA increased the expression level of microRNA-124 (miR-124). Furthermore, the inhibitory effect of FA on STAT3 was counteracted by the treatment of miR-124 inhibitor. Critically, FA ameliorated LPS-induced ALI pathological damage, the increase in lung water content and inflammatory cytokine, cells infiltration and activation of the STAT3 signaling pathway in BALB/c mice. Meanwhile, FA up-regulated the expression of miR-124 in lungs, while administration with miR-124 inhibitor attenuated the protective effects of FA. Our results indicated that FA alleviates LPS-induced inflammation through up-regulating miR-124 in vitro and in vivo. These findings indicate the potential of FA and miR-124 in the treatment of ALI.

Keywords: Forsythoside A; STAT3; acute lung injury; lipopolysaccharide; miR-124.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Lung Injury / chemically induced*
  • Acute Lung Injury / genetics*
  • Animals
  • Glycosides / chemistry
  • Glycosides / pharmacology*
  • Inflammation / genetics
  • Inflammation / pathology
  • Interleukin-6 / metabolism
  • Lipopolysaccharides
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Male
  • Mice
  • Mice, Inbred BALB C
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Models, Biological
  • Protective Agents / chemistry
  • Protective Agents / pharmacology*
  • RAW 264.7 Cells
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction / drug effects
  • Tumor Necrosis Factor-alpha / metabolism
  • Up-Regulation / drug effects
  • Up-Regulation / genetics*

Substances

  • Glycosides
  • Interleukin-6
  • Lipopolysaccharides
  • MicroRNAs
  • Mirn124 microRNA, mouse
  • Protective Agents
  • STAT3 Transcription Factor
  • Tumor Necrosis Factor-alpha
  • forsythiaside