Paeoniflorin Promotes Angiogenesis in A Vascular Insufficiency Model of Zebrafish in vivo and in Human Umbilical Vein Endothelial Cells in vitro.
OBJECTIVE
To investigate the pro-angiogenic effects of paeoniflorin (PF) in a vascular insufficiency model of zebrafish and in human umbilical vein endothelial cells (HUVECs).


METHODS
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.


RESULTS
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.


CONCLUSIONS
PF could promote angiogenesis in a vascular insufficiency model of zebrafish in vivo and in HUVECs in vitro.
Clinical Medical College, Beijing University of Chinese Medicine, Beijing, 100029, China.|State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao SAR, 999078, China.|Laboratory of Cardiovascular Diseases, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China.
Qi-Qi
QQ
Xin
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao SAR, 999078, China.
Bin-Rui
BR
Yang
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao SAR, 999078, China.
He-Feng
HF
Zhou
Clinical Medical College, Beijing University of Chinese Medicine, Beijing, 100029, China.|Laboratory of Cardiovascular Diseases, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China.
Yan
Y
Wang
Department of Pharmaceutical Preparation, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China.
Bo-Wen
BW
Yi
Laboratory of Cardiovascular Diseases, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China.
Wei-Hong
WH
Cong
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao SAR, 999078, China.
Simon Ming-Yuen
SM
Lee
Laboratory of Cardiovascular Diseases, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China. kjchenvip@163.com.
Ke-Ji
KJ
Chen
D043925:Angiogenesis Inducing Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D030801:Animals, Genetically Modified; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use; D004625:Embryo, Nonmammalian; D005960:Glucosides / Q000494:pharmacology / Q000627:therapeutic use*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D039821:Monoterpenes / Q000494:pharmacology / Q000627:therapeutic use*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D008517:Phytotherapy; D014652:Vascular Diseases / Q000188:drug therapy* / Q000473:pathology*; D015027:Zebrafish; D006027:Glycosides
D043925:Angiogenesis Inducing Agents; D004365:Drugs, Chinese Herbal; D005960:Glucosides; D039821:Monoterpenes; C015423:peoniflorin; D006027:Glycosides
angiogenesis; human umbilical vein endothelial cell; paeoniflorin; zebrafish