Anti-inflammatory effects of vicenin-2 and scolymoside in vitro and in vivo

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. 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. 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-alpha (TNF-alpha) or Interleukin (IL)-6 and the activation of nuclear factor-kappa B (NF-kappa B) or extracellular regulated kinases (ERK) 1/2 by LPS. Moreover, post-treatment with each compound resulted in reduced LPS-induced lethal endotoxemia. 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.