Table 1.

Bioactivities of fucoidan from different species ^*.

Activity	Species	Experiment setting	Key findings	Refs
Anti-coagulant and Anti-thrombotic	Fucus vesiculosus; Undaria pinnatifida; Fucus evanescens	immobilized on plasma treated PET; in vitro anticoagulant assay	prolonged TT and APTT	(Kim et al., 2010; Kuznetsova et al., 2003; Ozaltin et al., 2019; Zhang et al., 2015)
	Laminaria hyperborean	lepirudin-based human whole blood model in vitro anticoagulant assay; in	inhibited coagulation above 100 μg/mL; stimulated coagulation at 10 μg/mL slowed thrombosis formation, increased	(Kopplin et al., 2018)
	Saccharina japonica	vivo arterial thrombosis rat model; oral administration in human	TFPI; prolonged APTT and TT; inhibited thrombin-induced platelet aggregation; shortened lysis time of thrombus	(Ren et al., 2013; Zhang et al., 2015; Zhao et al., 2012; Zhao et al., 2016)
	Ecklonia maxima	in vitro anticoagulant assay	increased APTT	(Zhang et al., 2015)
	Ecklonia cava	in vitro anticoagulant assay	prolonged bleeding time	(Wijesinghe et al., 2011)
	Hizikia fusiforme	in vitro anticoagulant assay	prolonged APTT distinctly, but delayed TT little	(Li, Zhao, et al., 2008)
	Ascophyllum nodosum	in vitro anticoagulant assay	bound to antithrombin in a 1:1 stoichiometry	(Varenne, Gareil, Colliec-Jouault, & Daniel, 2003)
	Turbinaria conoides	in vitro anticoagulant assay	prolonged both APTT and PT	(Ganapathy et al., 2019)
	Holothuria edulis; Ludwigothurea grisea	in vitro anticoagulant assay	prolonged APTT, but not PT nor TT; inhibited thrombin and factor Xa	(Wu et al., 2015)
	Holothuria polii	in vitro anticoagulant assay	inhibited thrombin with the presence of heparin cofactor II and antithrombin III	(Mansour et al., 2019)
	Isostichopus badionotus	in vitro anticoagulant assay	improved antithrombin activity on thrombin and factor Xa	(Chen et al., 2012)
Platelet	Fucus vesiculosus	in vitro platelet rich plasma	induced irreversible platelet aggregation and activation through SFK-dependent pathways; increased CD62p and CD63 positive platelets	(Carvalho G. de Azevedo et al., 2009; Dürig et al., 1997; Kardeby et al., 2019; Manne et al., 2013)
	Saccharina japonica	in vivo intravenous injection of LMWF at 10 mg/kg	inhibit activation of platelets by reducing platelet aggregation	(Chen et al., 2016; Zhu et al., 2010)
	Holothuria edulis; Ludwigothurea grisea	in vitro citrated human platelet rich plasma;	did not induce platelet aggregation at various concentrations (7.5–30 μg/mL)	(Wu et al., 2015)
Anti-complement	Saccharina japonica; Sargassum thunbergii	in vitro	anticomplement activity	(Jin, Liu, Zhong, Sun, & Zhang, 2017; Liu et al., 2018)
	Laminaria hyperborea	lepirudin-based human whole blood model	sulfation and high molecular weight are important in anticomplement activity	(Kopplin et al., 2018)
	Saccharina latissimi; Fucus vesiculosus	in vitro	reduced IL-8 and C5a-induced calcium release by binding to IL-8 and C5a in a concentration-dependent manner	(Liewert, Ehrig, & Alban, 2017)
	Ascophyllum nodosum	MALDI-TOF mass spectroscopy; in vitro hemolytic assay in whole serum	bound to C1q; blocked the dissociation of C2 and C4, to a lesser extent of C3	(Clément et al., 2010; Tissot, Daniel, et al., 2003; Tissot et al., 2005; Tissot, Montdargent, et al., 2003)
	Laminaria cichorioides; fucus evanescens	in vitro assay with human serum	caused 50% inhibition of alternative pathway of complement	(Zvyagintseva et al., 2000)
Inhibit selectin	Sargassum fusiforme	in vitro static and flow chamber	blocked P-selectin mediated adhesion of neutrophil	(Wu et al., 2019)
	Saccharina japonica	diabetic nephropathy rat	decreased the level of P-selectin and selectin-dependent inflammatory cytokines	(Xu, Zhang, Luo, Wang, & Duan, 2016)
	Sacharina latissima	in vitro binding activity	inhibited L- and P-selectin	(Ushakova et al., 2005)
Endothelial cells	Fucus vesiculosus; Ascophyllum nodosom	layer-by-layer stent coating with laminin; polyvinyl alcohol hydrogels; decellularized pulmonary heart valve	promoted endothelial cell adhesion and proliferation	(Marinval et al., 2018; Yao et al., 2020; Ye et al., 2016)
	Fucus evanescens	dyslipidemia mice model	reduced levels of endothelin-1 and TNFα, IFNγ in blood serum.	(Kuznetsova et al., 2019)
	Ascophyllum nodosom	EPC proliferation and adhesion; in vitro tube formation assay	promoted proangiogenic phenotype, proliferation and migration of EPCs	(Roux et al., 2012)
	Undaria piniatifida	HUVEC proliferation, migration, and tube formation	reduced HUVEC proliferation and migration; inhibited tube formation	(Liu et al., 2012)
Anti-proliferation	Fucus vesiculosus	in vitro cell culture; in vivo injection; fucoidan coated stent	inhibited SMC proliferation and migration; interacted with TGF-β1; reduced restenosis	(Kim et al., 2015; McCaffrey et al., 1992; Novoyatleva et al., 2019; Religa et al., 2000)
	Saccharina japonica	in vitro cell culture; in vivo in ApoE (−/−) mouse model	inhibited SMC proliferation and migration; reduced atherosclerosis	(Xu et al., 2019)
	Undaria pinnatifida	in vivo in eNOS inhibition-induced hypertensive rat model	reduced media thickening and SMC proliferation	(Li et al., 2016)
	Ascophyllum nodosum	in vitro cell culture; balloon-induced thoracic aorta injury rat model	inhibited SMC growth and migration; inhibited collagen synthesis; reduced intimal hyperplasia	(Hlawaty et al., 2011; Logeart et al., 1996)

^*The extended version of the table is provided in the Supplementary Table 1