vicenin-ii and Pulmonary-Edema

Transforming growth factor β-induced protein (TGFBIp) is an extracellular matrix protein whose expression in several cell types is greatly increased by TGF-β. TGFBIp is released by the human umbilical vein endothelial cells (HUVECs) and functions as a mediator of experimental sepsis. Cyclopia subternata is a medicinal plant commonly used in traditional medicine to relieve pain in biological processes. In this study, we investigated the antiseptic effects and underlying mechanisms of vicenin-2 and scolymoside, two active compounds in C. subternata against TGFBIp-mediated septic responses in HUVECs and mice. The anti-inflammatory activities of vicenin-2 or scolymoside were determined by measuring permeability, human neutrophils adhesion and migration, and activation of pro-inflammatory proteins in TGFBIp-activated HUVECs and mice. According to the results, vicenin-2 or scolymoside effectively inhibited lipopolysaccharide-induced release of TGFBIp and suppressed TGFBIp-mediated septic responses, such as hyperpermeability, adhesion and migration of leukocytes, and expression of cell adhesion molecules. In addition, vicenin-2 or scolymoside suppressed the production of tumor necrosis factor-α and interleukin 6 and activation of nuclear factor-κB and extracellular regulated kinases 1/2 by TGFBIp. Vicenin-2 or scolymoside reduced cecal ligation and puncture (CLP)-induced septic mortality and pulmonary injury. Collectively, these results indicate that vicenin-2 and scolymoside could be a potential therapeutic agent for treatment of various severe vascular inflammatory diseases via inhibition of the TGFBIp signaling pathway.

Topics: Animals; Anti-Inflammatory Agents; Apigenin; Capillary Permeability; Cell Adhesion; Cell Adhesion Molecules; Cells, Cultured; Chemotaxis, Leukocyte; Cyclopia Plant; Disease Models, Animal; Dose-Response Relationship, Drug; Enzyme Activation; Extracellular Matrix Proteins; Extracellular Signal-Regulated MAP Kinases; Glucosides; Human Umbilical Vein Endothelial Cells; Inflammation Mediators; Luteolin; Male; Mice, Inbred C57BL; Neutrophils; Phytotherapy; Plant Extracts; Plants, Medicinal; Pulmonary Edema; Sepsis; Time Factors; Transforming Growth Factor beta