Bibenzyl from Dendrobium inhibits angiogenesis and its underlying mechanism

Bibenzyl is a type of active compounds abundant in Dendrobium.  In the present study, we investigated the inhibitory effects of six bibenzyls isolated from Dendrobium species on vascular endothelial growth factor (VEGF)-induced tube formation in human umbilical vascular endothelial cells (HUVECs).  All those bibenzyls inhibited VEGF-induced tube formation at 10 μmol·L⁻¹ except tristin, and of which moscatilin was found to have the strongest activity at the same concentration.  The lowest effective concentration of moscatilin was 1 μmol·L⁻¹.  Further results showed that moscatilin inhibited VEGF-induced capillary-like tube formation on HUVECs in a concentration-dependent manner.  Western blotting results showed that moscatilin also inhibited VEGF-induced phosphorylation of VEGFR2 (Flk-1/KDR) and extracellular signal-regulated kinase 1/2 (ERK1/2).  Further results showed that moscatilin inhibited VEGF-induced activation of c-Raf and MEK1/2, which are both upstream signals of ERK1/2.  Taken together, results presented here demonstrated that moscatilin inhibited angiogenesis via blocking the activation of VEGFR2 (Flk-1/KDR) and c-Raf-MEK1/2-ERK1/2 signals.