peoniflorin and Vascular-Diseases

To investigate the pro-angiogenic effects of paeoniflorin (PF) in a vascular insufficiency model of zebrafish and in human umbilical vein endothelial cells (HUVECs).. In vivo, the pro-angiogenic effects of PF were tested in a vascular insufficiency model in the Tg(fli-1:EGFP)y1 transgenic zebrafish. The 24 h post fertilization (hpf) embryos were pretreated with vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor II (VRI) for 3 h to establish the vascular insufficiency model and then post-treated with PF for 24 h. The formation of intersegmental vessels (ISVs) was observed with a fluorescence microscope. The mRNA expression of fms-like tyrosine kinase-1 (flt-1), kinase insert domain receptor (kdr), kinase insert domain receptor like (kdrl) and von Willebrand factor (vWF) were analyzed by real-time polymerase chain reaction (PCR). In vitro, the pro-angiogenic effects of PF were observed in HUVECs in which cell proliferation, migration and tube formation were assessed.. PF (6.25-100 μmol/L) could rescue VRI-induced blood vessel loss in zebrafish and PF (25-100 μmol/L), thereby restoring the mRNA expressions of flt-1, kdr, kdrl and vWF, which were down-regulated by VRI treatment. In addition, PF (0.001-0.03 μmol/L) could promote the proliferation of HUVECs while PF stimulated HUVECs migration at 1.0-10 μmol/L and tube formation at 0.3 μmol/L.. PF could promote angiogenesis in a vascular insufficiency model of zebrafish in vivo and in HUVECs in vitro.

Topics: Angiogenesis Inducing Agents; Animals; Animals, Genetically Modified; Cells, Cultured; Disease Models, Animal; Drugs, Chinese Herbal; Embryo, Nonmammalian; Glucosides; Human Umbilical Vein Endothelial Cells; Humans; Monoterpenes; Neovascularization, Physiologic; Phytotherapy; Vascular Diseases; Zebrafish

Paeoniflorin (PF) extracted from the root of Paeonia lactiflora pall, displays anti-inflammation properties in several animal models. Adhesion molecules are important for the recruitment of leucocyte to the vessel wall and involved in the pathogenesis of various autoimmune and inflammatory diseases. Herein, we investigate the effects of PF on adhesion molecule expression in a mouse model of cutaneous Arthus reaction and cultured human dermal microvascular endothelial cells (HDMECs). We showed that PF significantly ameliorated the immune complex (IC) induced vascular damage, leucocyte infiltrates and adhesion molecules expression. Furthermore, PF markedly blocked tumor necrosis factor-α (TNF-α)-induced E-selectin and intercellular adhesion molecule-1 (ICAM-1) expression in HDMECs at both mRNA and protein levels. PF also suppressed TNF-α-induced adhesion of polymorphonuclear leucocytes (PMNs) to HDMECs. Finally, western blot data revealed that PF can inhibit the phosphorylation of p38, JNK in TNF-α-treated HDMECs. These data suggest that PF, as an anti-inflammatory agent, can downregulate adhesion molecules expression. PF may be a candidate medicine for the treatment of IC-induced inflammatory response.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antigen-Antibody Complex; Arthus Reaction; Autoimmunity; Benzoates; Bridged-Ring Compounds; Cell Adhesion; Cells, Cultured; Disease Models, Animal; E-Selectin; Endothelial Cells; Gene Expression Regulation; Glucosides; Humans; Inflammation; Intercellular Adhesion Molecule-1; Leukocytes; Male; MAP Kinase Kinase 4; Mice; Mice, Inbred BALB C; Microcirculation; Monoterpenes; p38 Mitogen-Activated Protein Kinases; Real-Time Polymerase Chain Reaction; Skin; Tumor Necrosis Factor-alpha; Vascular Diseases