Anti-angiogenic activity and mechanism of a chemically sulfated natural glucan from Phellinus ribis

A sulfated polysaccharide named PRP-S16 was obtained by sulfation of a glucan from Phellinus ribis using the chlorosulfonic acid method. PRP-S16 could significantly block the formation of new vessels in chicken chorioallantoic membrane (CAM). It could also inhibit the proliferation, migration, and tube formation and significantly reduced the mRNA expression of vascular endothelial growth factor (VEGF) in EA.hy926 endothelial cells. Western blotting indicated that PRP-S16 down regulated the protein expression of VEGF and VEGF receptor-1 (VEGFR-1), and inhibited the phosphorylation of VEGFR-2, protein kinase B (Akt) and extracellular signal-regulated kinase (ERK1/2) in EA.hy926 cells. These findings suggest that the mechanism of action of the anti-angiogenesis activity of PRP-S16 is related to the inhibition of VEGF-induced signaling pathway. PRP-S16 might be utilized as an effective antagonist in combating diseases associated with angiogenesis.