Anti-inflammatory activities of isorhamnetin-3-O-galactoside against HMGB1-induced inflammatory responses in both HUVECs and CLP-induced septic mice

Tae Hoon Kim, Sae Kwang Ku, Jong Sup Bae

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

High mobility group box 1 (HMGB1) protein is a crucial nuclear cytokine that elicits severe vascular inflammatory diseases. Oenanthejavanica (water dropwort) extract has anti-arrhythmic, neuroprotective and anti-diabetic activity. However, isorhamnetin-3-O-galactoside (I3G), an active compound from O. javanica, is not researched well for its biological activity. Here, we investigated the anti-inflammatory activities of I3G by monitoring the effects of I3G on the lipopolysaccharide (LPS) or cecal ligation and puncture (CLP)-mediated release of HMGB1 and HMGB1 or CLP-mediated modulation of inflammatory responses. I3G potently inhibited the release of HMGB1 and down-regulated HMGB1-dependent inflammatory responses in human endothelial cells. I3G also inhibited HMGB1-mediated hyperpermeability and leukocyte migration in mice. Further studies revealed that I3G suppressed the production of tumor necrosis factor-α and activation of nuclear factor-κB by HMGB1. In addition, I3G reduced CLP-inducedHMGB1 release and sepsis-related mortality. Given these results, I3G should be viewed as a candidate therapeutic agent for the treatment of severe vascular inflammatory diseases such as sepsis or septic shock via inhibition of the HMGB1 signaling pathway.

Original languageEnglish
Pages (from-to)336-345
Number of pages10
JournalJournal of Cellular Biochemistry
Volume114
Issue number2
DOIs
StatePublished - Feb 2013

Keywords

  • Barrier integrity
  • HMGB1
  • Inflammation
  • Isorhamnetin-3-O-galactoside
  • Sepsis

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