Angiostatic effects of Brazilian green propolis and its chemical constituents

Propolis, a resinous substance collected by honeybees from various plant sources, has several pharmacological actions, such as anti-tumor and anti-inflammatory effects. The aim of this study was to evaluate the anti-angiogenic effects of a water extract of Brazilian green propolis (WEP) and its constituents, caffeoylquinic acid derivatives, against angiogenic processes in human umbilical vein endothelial cells (HUVECs) in vitro. We also examined the anti-angiogenic effects of WEP against retinal neovascularization in a murine oxygen-induced retinopathy model in vivo. WEP and its constituents significantly suppressed vascular endothelial growth factor (VEGF)-induced HUVEC proliferation, migration, and tube formation in vitro. WEP and its caffeoylquinic acid derivatives suppressed VEGF-stimulated phosphorylation of mitogen-activated protein kinase in HUVECs (versus VEGF alone). Moreover, WEP (300 mg/kg/day, subcutaneously. for 5 days) significantly suppressed retinal neovascularization in the murine oxygen-induced retinopathy model. These data indicate that (i) WEP has angiostatic effects against angiogenic processes in vitro and in an in vivo model of murine oxygen-induced retinopathy and (ii) the inhibitory effects of WEP against in vitro angiogenesis are chiefly derived from its caffeoylquinic acid derivatives. Judging from these findings, WEP and its caffeoylquinic acid derivatives may represent candidates for preventive or therapeutic agents against diseases caused by angiogenesis.