Inhibitory effects of Paeonia suffruticosa Andrews extracts on VEGF binding to VEGF receptor

Tumor angiogenesis is a critical step for the growth and metastasis of solid tumors. Vascular endothelial growth factor (VEGF) is the most important angiogenic molecule associated with tumor-induced neovascularization. VEGF exerts its activity through binding to its receptor tyrosine kinase, KDR/Flk-1, expressed on the surface of endothelial cells. This study was carried out to investigate inhibitory effect of extracts from root cortex of Paeonia suffruticosa Andrews on VEGF binding to VEGF receptor. The MeOH extract from P. suffruticosa Andr. inhibited the binding of KDR/Flk-1-Fc to immobilized VEGF₁₆₅ more than 45% at the concentration of 100 μg/mL. The MeOH extract was further fractionated into n-hexane, ethyl acetate, n-BuOH, and aqueous fractions. Among the four fractions, the ethyl acetate fraction from the root cortex of P. suffruticosa Andr. exhibited highly effective inhibition (≈ 79% inhibition) and then n-BuOH fraction (≈ 45% inhibition) on the binding of KDR/Flk-1-Fc to immobilized VEGF¹⁶⁵ at the concentration of 100 μg/mL. The ethyl acetate fraction from the root cortex of P. suffruticosa Andr. more efficiently blocked VEGF-induced human umbilical vein endothelial cell proliferation, than the growth of HT1080 human fibrosarcoma. Our results suggest that P. suffruticosa Andr. may be used as a candidate for developing anti-angiogenic agent.