Sanguiin H-6 blocks endothelial cell growth through inhibition of VEGF binding to VEGF receptor

The vascular endothelial growth factor (VEGF) plays a key role in angiogenesis, which is a process where new blood vessels develop from the endothelium of a pre-existing vasculature. VEGF exerts its activity by binding to its receptor tyrosine kinase, KDR/Flk-1, which is expressed on the surface of endothelial cells. A methanol extract and organic solvent (n-hexane, ethyl acetate, n-butanol, aqueous) fractions from Rubus coreanus were examined for their inhibitory effects on VEGF binding to the VEGF receptor. The methanol extract from the crude drug were found to significantly inhibit VEGF binding to the VEGF receptor (IC₅₀ ≈ 27 μg/mL). Among the fractions examined, the aqueous fraction from the medicinal plant showed potent inhibitory effects against the binding of KDR/Flk-1-Fc to immobilized VEGF₁₆₅ in a dose-dependent manner (IC₅₀ ≈ 11 μg/mL). Sanguiin H-6 was isolated as an active principle from the aqueous fraction, and inhibited the binding of KDR/Flk-1-Fc to immobilized VEGF₁₆₅ in a dose-dependent manner (IC₅₀ ≈ 0.3 μg/mL). In addition, sanguiin H-6 efficiently blocked the VEGF-induced HUVEC proliferation in a dose-dependent manner (IC₅₀ ≈ 7.4 μg/mL) but had no effect on the growth of HT1080 human fibrosarcoma cells. This suggests that sanguiin H-6 might be a potential anti-angiogenic agent.