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  • Orientin inhibits HMGB1-induced inflammatory responses in HUVECs and in murine polymicrobial sepsis.

Orientin inhibits HMGB1-induced inflammatory responses in HUVECs and in murine polymicrobial sepsis.

Inflammation (2014-04-29)
Hayoung Yoo, Sae-Kwang Ku, Taeho Lee, Jong-Sup Bae
ABSTRACT

High mobility group box-1 (HMGB1) protein acts as a late mediator of severe vascular inflammatory conditions. Orientin has been known to have anxiolytic and antioxidative activities. However, the effect of orientin on HMGB1-induced inflammatory response has not been studied. We assessed this question by monitoring the effects of post-treatment orientin and its derivatives on lipopolysaccharide (LPS) and cecal ligation and puncture (CLP)-mediated release of HMGB1 and HMGB1-mediated regulation of pro-inflammatory responses in human umbilical vein endothelial cells (HUVECs) and septic mice. Post-treatment orientin was found to suppress LPS-mediated release of HMGB1 and HMGB1-mediated cytoskeletal rearrangements. Orientin inhibited HMGB1-mediated hyperpermeability and leukocyte migration in septic mice. Orientin also induced down-regulation of CLP-induced release of HMGB1 and mortality. Collectively, these results suggest that orientin may be regarded as a candidate therapeutic agent for treatment of vascular inflammatory diseases via inhibition of the HMGB1 signaling pathway.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Lipopolysaccharides from Escherichia coli O111:B4, Ready Made solution, 1 mg/mL
Sigma-Aldrich
2-Mercaptoethanol, BioUltra, for molecular biology, ≥99.0% (GC)
Sigma-Aldrich
2-Mercaptoethanol, ≥99.0%
Sigma-Aldrich
Rat Interleukin-6 ELISA Kit, for for cell lysate and tissue lysate
Sigma-Aldrich
Rat IL-6 ELISA Kit, for serum, plasma and cell culture supernatants
Sigma-Aldrich
Mouse IL-6 R ELISA Kit, for serum, plasma and cell culture supernatant
Isoorientin, primary reference standard
Supelco
2-Mercaptoethanol, for HPLC derivatization, LiChropur, ≥99.0% (GC)
Sigma-Aldrich
Isoorientin, ≥98% (HPLC)
Sigma-Aldrich
2-Mercaptoethanol, for molecular biology, suitable for electrophoresis, suitable for cell culture, BioReagent, 99% (GC/titration)
Sigma-Aldrich
Isovitexin, ≥98.0% (HPLC)
Supelco
Vitexin, analytical standard
Sigma-Aldrich
Fluorescein, for fluorescence, free acid
Sigma-Aldrich
HMG-1 human, lyophilized powder, ≥90% (SDS-PAGE), Histidine-tagged, recombinant, expressed in E. coli
Isovitexin, primary reference standard
Sigma-Aldrich
Mouse IL-6 ELISA Kit, for serum, plasma and cell culture supernatant
Sigma-Aldrich
Mouse IL-6 ELISA Kit, for cell and tissue lysates
Vitexin, primary reference standard
Fluorescein, European Pharmacopoeia (EP) Reference Standard