Engeletin Alleviates Lipopolysaccharide-Induced Endometritis in Mice by Inhibiting TLR4-mediated NF-κB Activation

J Agric Food Chem. 2016 Aug 10;64(31):6171-8. doi: 10.1021/acs.jafc.6b02304. Epub 2016 Jul 28.

Abstract

Engeletin (dihydrokaempferol 3-rhamnoside) is a flavanonol glycoside. It can be found in the skin of white grapes and white wine and is widely distributed in southeast Asia, and the leaves are used in a tea. Here, we explored the impact of engeletin against the inflammatory reaction in a lipopolysaccharide (LPS)-induced endometritis mouse model. Engeletin treatment significantly attenuated uterus damage and decreased myeloperoxidase activity. ELISA and qPCR assays showed that engeletin dose-dependently suppressed the expression of TNF-α, IL-1β, and IL-6. Molecular studies also demonstrated that the levels of iNOS, COX-2, and TLR4, along with their downstream molecules MyD88, IRAK1, TRAF6, and TAK1, were also suppressed by engeletin. In addition, engeletin treatment inhibited NF-κB signaling-pathway activation. Moreover, immunofluorescence analysis demonstrated that engeletin suppressed NF-κB-p65 nuclear translocation. These data indicated the protective action of engeletin against LPS-stimulated endometritis in mice via negative regulation of pro-inflammatory mediators via the TLR4-regulated NF-κB pathway.

Keywords: anti-inflammatory; dihydrokaempferol 3-rhamnoside; endometritis; engeletin; flavanonol glycoside.

MeSH terms

  • Animals
  • Endometritis / chemically induced
  • Endometritis / drug therapy*
  • Endometritis / genetics
  • Endometritis / metabolism
  • Female
  • Flavonols / administration & dosage*
  • Flavonols / chemistry
  • Glycosides / administration & dosage*
  • Glycosides / chemistry
  • Humans
  • Lipopolysaccharides / adverse effects
  • Mice
  • Mice, Inbred BALB C
  • NF-kappa B / genetics
  • NF-kappa B / metabolism*
  • Signal Transduction
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 4 / metabolism*

Substances

  • Flavonols
  • Glycosides
  • Lipopolysaccharides
  • NF-kappa B
  • Tlr4 protein, mouse
  • Toll-Like Receptor 4
  • engeletin