Angiogenic pathway inhibition of Corydalis yanhusuo and berberine in human umbilical vein endothelial cells.
Corydalis yanhusuo, a well-known traditional Chinese medicine, is widely used in China as an analgesic for patients with terminal cancer. In this study, we want to expose the antiangiogenic effects and the underlying mechanisms of C. yanhusuo and the alkaloids obtained from this plant. The constituents of C. yanhusuo were first investigated for their inhibitory effects on angiogenesis, using several bioassays, including vascular endothelial growth factor (VEGF)-induced human umbilical vein endothelial cell (HUVEC) proliferation, migration, invasion, and tube formation. To determine the active antiangiogenic compounds in C. yanhusuo, we studied the antiproliferative activities of several main constituents of C. yanhusuo, which belong to a group of protoberberine alkaloids, on HUVECs and identified berberine as a powerful angiogenesis inhibitor in C. yanhusuo. Both C. yanhusuo extract and its active compound berberine significantly suppressed the VEGF-induced upregulation of matrix metalloproteinase 2 (MMP2) at both mRNA and protein levels. Their functional effects, including the inhibition of MMP2, were shown to be involved VEGF-triggered ERK1/2 pathways. Our findings provide novel insights into the antiangiogenic effects of C. yanhusuo and berberine, and offer scientific evidence for their traditional clinical application as a cancer treatment.
Gao
Jian-Li
JL
Institute of Chinese Medical Sciences, University of Macau, Macao, China. jianligao@gmail.com
Shi
Jun-Min
JM
Lee
Simon Ming-yuen
SM
Zhang
Qing-Wen
QW
Wang
Yi-Tao
YT
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D001599:Berberine / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D031311:Corydalis; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D042783:Endothelial Cells / Q000187:drug effects* / Q000502:physiology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D014471:Umbilical Veins; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology
D020533:Angiogenesis Inhibitors; D004365:Drugs, Chinese Herbal; D010936:Plant Extracts; D042461:Vascular Endothelial Growth Factor A; D001599:Berberine; D016222:Fibroblast Growth Factor 2; D048049:Extracellular Signal-Regulated MAP Kinases; D020778:Matrix Metalloproteinase 2