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. 2020 Jul 22;18(8):376. doi: 10.3390/md18080376

Table 1.

Distribution of molecular targets and related biologic activity interacting with fucoidan.

Molecular Targets Cell Types Biologic Activity of Interaction with Fucoidan Reference
Scavenger receptors
SR-A Macrophages, endothelial cells, lung epithelial cells, microglia, astrocytes, primary murine fibroblasts

  1. Cooperative with Toll-like receptors 4 (TLR4), mediating intracellular signaling cascades

  2. Internalization of fucoidan

  3. Crosstalk with endoplasmic reticulum stress (ERS) pathway, promoting cancer cells apoptosis

 [10,11,12,13,14,15,16,17,18,19,20,21,22,23,24]
Toll-like receptors
TLR2 Macrophages, monocytes, dendritic cells, mast cells, neutrophils, natural killer (NK) cells fibroblasts, embryonic kidney cells Activating the nuclear factor-κB (NF-κB) [19,25,26]
TLR4 Macrophages, monocytes, dendritic cells
mast cells, neutrophils, b lymphocytes,
intestinal epithelium cells, cardiomyocytes, renal tubular epithelial and endothelial cells, podocytes, Kupffer cells, lung cancer cells

  1. Activating NF-κB and mitogen-activated protein kinase (MAPK) signaling pathways

  2. Induces reactive oxygen species (ROS) associated ERS, resulting in cancer cells apoptosis

 [18,19,25,26,27,28,29,30,31]
C-type lectins
Ly-49 NK cells, subset of T lymphocytes Blocking cell adhesion [32,33]
OCIL Macrophages, epithelial cells, mesenchymal cells, dendritic cells, lymphocytes Cannot affect osteoclast inhibitory lectin (OCIL) inhibition of osteoclast formation [34]
CLEC-2 Platelets, (low levels in immune cells), gastric epithelial cells

  1. Activating tyrosine kinase-dependent signaling pathway, resulting in platelet aggregation

  2. Preventing expression of phosphoinositol 3 kinase (PI3K) subunits in a spleen tyrosine kinase (Syk)) dependent manner and suppresses metastasis of gastric cancer cells

 [35,36,37,38,39]
L-selectin Monocytes, dendritic cells, neutrophils, NK cells, B lymphocytes, T lymphocytes

  1. Deleting endothelial-leukocyte interactions

  2. Inhibiting leukocyte urokinase plasminogen activator receptors-mediated Ca2+ mobilization

 [40,41,42]
P-selectin Platelets, endothelial cell, Kupffer cells Attenuating microvascular platelet deposition and platelet-mediated myocardial injury [40,41,43,44,45]
Other affinity molecules of fucoidan
CR3 Macrophages, monocytes, neutrophils, NK cells Inhibiting adhesion of T84 cells to complement receptor 3 (CR3) [46,47,48,49]
αVβ3 Cancer cells, rapidly dividing endothelial cells Suppressing metastasis of gastric cancer cells though Src/cortactin/ E2F transcription factor 1 (E2F1) signaling pathway [50]
VEGF N/A Impeding vascular endothelial growth factors (VEGF)–VEGF receptor 2 (VEGFR2) interaction [51,52]
CXCL12/CXCR4 N/A Blocking both C–X–C motif chemokine 12 (CXCL12) induced C–X–C motif chemokine receptor type 4 (CXCR4) activation [53]
Elastin peptide receptor Mesenchymal cells, vascular smooth muscle cells, skin fibroblasts Recruiting monocytes through binding to elastin peptide receptor of monocytes [54,55]
TGF-β1 N/A Exerting functions of anti-fibrosis through blocking transforming growth factor-β (TGF-β1) interacted with its receptor [56,57]
ECM proteins N/A Suppressing metastasis of cancer cells though blocking extracellular matrix (ECM) proteins [58]