Vascular barrier protective effects of pellitorine in LPS-induced inflammation in vitro and in vivo

Pellitorine (PT), an active amide compound, is well known to possess insecticidal, antibacterial and anticancer properties. In this study, we first investigated the possible barrier protective effects of pellitorine against pro-inflammatory responses induced by lipopolysaccharide (LPS) and the associated signaling pathways in vitro and in vivo. The barrier protective activities of PT were determined by measuring permeability, monocyte adhesion and migration, and activation of pro-inflammatory proteins in LPS-activated human umbilical vein endothelial cells (HUVECs) and in mice. We found that PT inhibited LPS-induced barrier disruption, expression of cell adhesion molecules (CAMs) and adhesion/transendothelial migration of monocytes to human endothelial cells. PT also suppressed LPS-induced hyperpermeability and leukocyte migration in vivo. Further studies revealed that PT suppressed the production of tumor necrosis factor-alpha (TNF-alpha) or Interleukin (IL)-6 and activation of nuclear factor-kappa B (NF-kappa B) or extracellular regulated kinases (ERK) 1/2 by LPS. Moreover, treatment with PT resulted in reduced LPS-induced lethal endotoxemia. These results suggest that PT protects vascular barrier integrity by inhibiting hyperpermeability, expression of CAMs, and adhesion and migration of leukocytes, thereby endorsing its usefulness as a therapy for vascular inflammatory diseases. (C) 2013 Elsevier B.V. All rights reserved.