Total saponins from Albizia julibrissin inhibit vascular endothelial growth factor-mediated angiogenesis in vitro and in vivo.

Abstract

Dried stem bark from Albizia julibrissin (AJ) is a highly valued Traditional Chinese Medicine, which has been shown to suppress tumor growth and angiogenesis. Total saponins from AJ (TSAJ) are one of the most bioactive components of AJ extract. The present study evaluated the anti-tumor and anti-angiogenic effects of TSAJ in vitro and in vivo. The anti-angiogenic activity of TSAJ was investigated by measuring the effects on vascular endothelial growth factor (VEGF)-induced proliferation, migration and tube formation of Ea.hy926 endothelial cells in vitro. The expression levels of proteins associated with VEGF-induced angiogenesis were determined by western blotting. Furthermore, in vivo Matrigel™ plug and H22 hepatoma tumor models were used to verify the anti-angiogenic effects of TSAJ. The present study demonstrated that TSAJ significantly inhibited VEGF-mediated endothelial cell proliferation, migration and tube formation of Ea.hy926 cells in vitro. The anti-angiogenic effects of TSAJ were modulated by suppression of phosphorylated-(p-) focal adhesion kinase, p-Akt, and p-extracellular signal-regulated kinase in the VEGF/VEGF receptor 2 (R2) signaling pathway. Furthermore, oral administration of TSAJ significantly inhibited tumor growth and tumor-induced angiogenesis, as well as the formation of functional vessels, in the Matrigel™ plug model. These results suggest that TSAJ may be a potential anti-angiogenic agent that targets the VEGF/VEGFR2 signaling pathway, and inhibits tumor-induced angiogenesis.