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.