Angiogenic effect of saponin extract from Panax notoginseng on HUVECs in vitro and zebrafish in vivo.
Angiogenesis plays an important role in a wide range of physiological processes such as wound healing and fetal development. In fact, many diseases are associated with imbalance in the regulation of angiogenesis in which there is either excessive or insufficient blood vessel formation. Panax notoginseng, a blood circulation invigorating herb, is commonly used in traditional Chinese medicine to treat circulation-related diseases. However, the biological effects of saponin extract from Panax notoginseng (PNS) on angiogenesis and the underlying mechanisms are yet to be fully elucidated. This investigation describes the angiogenic effects of PNS on human umbilical vein endothelial cells (HUVECs) in vitro and zebrafish in vivo. The 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)5[(phenylamino)carbonyl]2H-tetrazolium hydroxide (XTT) assay and microscopic cell counting demonstrated that the extract was able to stimulate the proliferation of HUVECs. Meanwhile, the numbers of invaded cells and tube branches were significantly increased in PNS treatment groups. PNS was also shown to promote changes in the subintestinal vessels, a feature of angiogenesis, in zebrafish. In addition, by using real-time polymerase chain reaction (PCR), PNS was found to enhance vascular endothelial growth factor (VEGF) and kinase-domain region/fetal liver kinase-1 in mice (KDR/Flk-1) mRNA expression, and the PNS-induced HUVECs proliferation could be abolished by a KDR/Flk-1 inhibitor. Furthermore, the proliferation of HUVECs induced by PNS was significantly attenuated by inhibitors of PI3K-Akt-eNOS. All the results suggest that PNS can promote angiogenesis, and that the proangiogenic effects involve the VEGF-KDR/Flk-1 and PI3K-Akt-eNOS signaling pathways.
Hong
Si-Jia
SJ
Institute of Chinese Medical Sciences, University of Macau, Av. Padre Tomás Pereira SJ, Taipa, Macao, China.
Wan
Jian-Bo
JB
Zhang
Yi
Y
Hu
Guang
G
Lin
Hui-Chao
HC
Seto
Sai Wang
SW
Kwan
Yiu-Wa
YW
Lin
Zhi-Xiu
ZX
Wang
Yi-Tao
YT
Lee
Simon Ming-Yuen
SM
D043925:Angiogenesis Inducing Agents / Q000494:pharmacology*; D000818:Animals; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D004625:Embryo, Nonmammalian / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects; D006801:Humans; D051379:Mice; D015394:Molecular Structure; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D053723:Panax notoginseng / Q000737:chemistry*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D012503:Saponins / Q000494:pharmacology; D015398:Signal Transduction; D014471:Umbilical Veins / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D015027:Zebrafish / Q000378:metabolism*
D043925:Angiogenesis Inducing Agents; D010936:Plant Extracts; D012503:Saponins; D042461:Vascular Endothelial Growth Factor A; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D019869:Phosphatidylinositol 3-Kinases; D040301:Vascular Endothelial Growth Factor Receptor-2