Mogroside IIIE Attenuates LPS-Induced Acute Lung Injury in Mice Partly Through Regulation of the TLR4/MAPK/NF-κB Axis via AMPK Activation

Phytother Res. 2017 Jul;31(7):1097-1106. doi: 10.1002/ptr.5833. Epub 2017 May 17.


Acute lung injury (ALI) often leads to high mortality, and there is as yet no effective drug treatment. The present study aimed to investigate protective effects of mogroside IIIE (MGIIIE, a cucurbitane-type triterpenoid from Siraitia grosvenorii Fruits) in experimental ALI and its underlying mechanism. MGIIIE (1, 10 0r 20 mg/kg) was orally administered for 1 h before a single intratracheal administration of lipopolysaccharide (LPS, 5 mg/kg). MGIIIE treatment dose-dependently suppressed pulmonary oedema, pro-inflammatory mediators (IL-1β, IL-6, TNF-α and HMGB1) release and higher MPO activity in lung tissues induced by LPS challenge. Molecular researches showed that mogroside IIIE (20 mg/kg) not only increased the phosphorylation of adenosine 5'-monophosphate-activated protein kinase (AMPK) but suppressed the over-expression of toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88). In addition, MGIIIE also inhibited the activation of MAPKs and nuclear factor κB (NF-κB) signalling in lung tissues from LPS-challenged mice. Similar antiinflammatory effects of MGIIIE were obtained in LPS-treated macrophages. Compound C (a pharmacological AMPK inhibitor) obviously reversed the antiinflammatory effect of MGIIIE in LPS-induced ALI mice. Taken together, AMPK activation plays a crucial role in the antiinflammatory effects of MGIIIE in LPS-induced ALI by down-regulating TLR4/MAPK/NF-κB signalling pathways. Copyright © 2017 John Wiley & Sons, Ltd.

Keywords: AMPK; TLR4; acute lung injury; lipopolysaccharide; mogroside IIIE.

MeSH terms

  • AMP-Activated Protein Kinases / metabolism*
  • Acute Lung Injury / chemically induced
  • Acute Lung Injury / drug therapy*
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Down-Regulation
  • Glucosides / pharmacology*
  • HMGB1 Protein
  • Interleukin-1beta / metabolism
  • Interleukin-6 / metabolism
  • Lipopolysaccharides
  • Lung / drug effects
  • Macrophages / drug effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mitogen-Activated Protein Kinases / metabolism*
  • Myeloid Differentiation Factor 88 / metabolism
  • NF-kappa B / metabolism*
  • Phosphorylation
  • Signal Transduction / drug effects
  • Toll-Like Receptor 4 / metabolism*
  • Triterpenes / pharmacology*
  • Tumor Necrosis Factor-alpha / metabolism


  • Anti-Inflammatory Agents
  • Glucosides
  • HMGB1 Protein
  • HMGB1 protein, mouse
  • IL1B protein, mouse
  • Interleukin-1beta
  • Interleukin-6
  • Lipopolysaccharides
  • Myd88 protein, mouse
  • Myeloid Differentiation Factor 88
  • NF-kappa B
  • Tlr4 protein, mouse
  • Toll-Like Receptor 4
  • Triterpenes
  • Tumor Necrosis Factor-alpha
  • interleukin-6, mouse
  • mogroside IIIE
  • Mitogen-Activated Protein Kinases
  • AMP-Activated Protein Kinases