A fucoidan from Nemacystus decipiens disrupts angiogenesis through targeting bone morphogenetic protein 4

A sulfated and acetylated fucoidan, named NDH01, was extracted from seaweed Nemacystus decipiens. NDH01 was composed of mannose, glucuronic acid, fucose, sulfate group and acetyl group in the molar ratio of 3.0: 14.4: 82.6: 34.3: 13.9. The backbone of NDH01 was fucose-free core, composed of alpha-D-1,2-Manp and beta-D-1,4-GlcpA disaccharide repeat unit. The branches were attached at the C3, C4 and C6 of alpha-D-1,2-Manp. The sidechain was composed of alpha-L-1,3,4-Fucp, alpha-L-1,4-Fucp, alpha-L-1,3-Fucp and alpha-L-1,4-GlcpA. The sulfate group was linked to C4 of alpha-L-1,3,4-Fucp, whereas, acetyl group was branched on C2 of alpha-L-1,2,3-Fucp. NDH01 could disrupt tube formation and inhibit the migration as well as cell growth of human microvascular endothelial cells. Besides, phosphorylation of Smad/1/5/8, Erk and FAK was significantly inhibited by NDH01. Further studies uncovered that NDH01 blocked Smad1/5/8 signaling via interacting with bone morphogenetic protein 4 and downregulating bone morphogenetic protein 4 expression. The results suggested that NDH01 might be an angiogenesis inhibitor through targeting bone morphogenetic protein 4. (C) 2016 Elsevier Ltd. All rights reserved.