Bojungbangdocktang inhibits vascular endothelial growth factor induced angiogenesis via blocking the VEGF/VEGFR2 signaling pathway in human umbilical vein endothelial cells

Oriental herbal medicines have been widely used for the prevention or treatment of various diseases including cancer in Asia. However, to prove their chemo preventive efficacies in modern times, scientific evidence for those herbal medicines is required. Thus, in the present study, an effective herbal cocktail Bojungbangdocktang (BJBDT) was investigated to elucidate antiangiogenic mechanism in vitro and in vivo. BJBDT significantly inhibited vascular endothelial growth factor (VEGF) induced proliferation in HUVECs at nontoxic concentrations, despite weak cytotoxicity against human umbilical vein endothelial cells (HUVECs). BJBDT also significantly suppressed VEGF-induced migration and tube formation of HUVECs. Furthermore, BJBDT treatment resulted in pale color and low hemoglobin level in Matrigel plugs, as well as dark red color and high hemoglobin level in untreated control. Interestingly, BJBDT specifically inhibited the binding of VEGF to vascular endothelial growth factor receptor 2 (VEGFR2), but not VEGFR1. In addition, friedelin, formononetin, ginsenoside Rb1, naringin, atractyloside, diosgenin, and allantonin were identified from BJBDT by high-performance liquid chromatography (HPLC) analysis as a quality of control. Taken together, these results suggest that BJBDT is a potent angiogenesis inhibitor blocking the VEGF/VEGFR2 signaling pathway in HUVECs. Supported by the Korea Science and Engineering Foundation Grant from the Korean Government (Ministry of Science and Technology) (Grant No. R13-2007-019-00000-0)