Anti-inflammatory effects of vicenin-2 and scolymoside in vitro and in vivo.
OBJECTIVE
Two structurally related flavonoids found in Cyclopia subternata, namely vicenin-2 and scolymoside, were examined for its effects on inflammatory responses by monitoring the effects of vicenin-2 and scolymoside on lipopolysaccharide (LPS)-mediated vascular inflammatory responses.


METHODS
The anti-inflammatory activities of vicenin-2 and scolymoside were determined by measuring permeability,monocytes adhesion and migration, and activation of pro-inflammatory proteins in LPS-activated HUVECs and mice.


RESULTS
We found that post-treatment of each compound inhibited LPS-induced barrier disruption, expression of cell adhesion molecules (CAMs), and adhesion/transendothelial migration of human neutrophils to human endothelial cells. Each compound induced potent inhibition of phorbol-12-myristate 13-acetate (PMA) and LPS-induced endothelial cell protein C receptor (EPCR)shedding. It also suppressed LPS-induced hyperpermeability and leukocytes migration in vivo. Furthermore,each compound suppressed the production of tumor necrosis factor-α (TNF-α) or Interleukin (IL)-6 and the activation of nuclear factor-κB (NF-κB) or extracellular regulated kinases (ERK) 1/2 by LPS. Moreover, posttreatment with each compound resulted in reduced LPS-induced lethal endotoxemia.


CONCLUSIONS
Vicenin-2 and scolymoside possess anti-inflammatory functions by inhibiting hyperpermeability,expression of CAMs, and adhesion and migration of leukocytes, thereby endorsing its usefulness as a therapy for vascular inflammatory diseases.
Hyejin
H
Kang
Sae-Kwang
SK
Ku
Byeongjin
B
Jung
Jong-Sup
JS
Bae
D051722:ADAM Proteins / Q000096:biosynthesis / Q000235:genetics; D000072198:ADAM17 Protein; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D047310:Apigenin / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002463:Cell Membrane Permeability / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D005960:Glucosides / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D047311:Luteolin / Q000494:pharmacology*; D008262:Macrophage Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000037:antagonists & inhibitors
D000893:Anti-Inflammatory Agents; D005960:Glucosides; D015850:Interleukin-6; D008070:Lipopolysaccharides; C530449:apigenin-6,8-di-C-glycopyranoside; C577686:interleukin-6, mouse; C458139:scolymoside; D047310:Apigenin; D051722:ADAM Proteins; D000072198:ADAM17 Protein; D047311:Luteolin; D013755:Tetradecanoylphorbol Acetate